Hairy Cell Leukemia
Conditions
Keywords
CAT-8015, Moxetumomab pasudotox
Brief summary
A dose-escalation study to identify the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), defined as the highest dose that can safely be given to a participant and establish the safest dose based on the highest tolerated dose for clinical testing.
Detailed description
A Phase 1, multicenter, dose escalation study of moxetumomab pasudotox (CAT-8015) in participants with relapsed or refractory hairy cell leukemia (HCL) to estimate the MTD, defined as the highest dose that can be safely administered to a patient, and to establish a safe dose, based on the MTD, for subsequent clinical testing (Phase 2 recommended dose).
Interventions
DRUGMoxetumomab Pasudotox (CAT 8015)
Participants received intravenous infusion of 5 microgram per kilogram (mcg/kg) moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
DRUGCAT 8015 (Moxetumomab Pasudotox)
Participants received intravenous infusion of 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Sponsors
Cambridge Antibody Technology
MedImmune LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
Confirmed diagnosis of HCL, Measurable disease, Participant's must have had at least 2 prior systemic therapies. There must have been at least 2 prior courses of purine analog, or 1 if the response to this course lasted less than (\<) 2 years, or if the participant had unacceptable toxicity to purine analog, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, Participant's with other cancers who meet eligibility criteria and have less than 5 years of disease free survival will be considered on a case-by-case basis, Life expectancy of greater than 6 months, as assessed by principal investigator, Must be able to understand and sign informed consent, Must be at least 18 years old, Female and male participants must agree to use an approved method of contraception during the study.
Exclusion criteria
- History of allogeneic bone marrow transplant, Documented and ongoing central nervous system involvement with their malignant disease (history of central nervous system (CNS) involvement is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 | Cycle 1 Day 1 and Day 5: pre-infusion, at 15 min during the infusion, at the end of infusion, and at 1, 1.5, 2, 4, 8, and 12 h post infusion | The Cmax accumulation ratio of moxetumomab pasudotox was calculated as the geometric mean ratio of Cmax on the last day and the first day of a multiple dose regimen: Day 5/Day 1. |
| Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion | Systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by AUC(0-infinity). |
| Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion | The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z). |
| Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion | The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z). |
| AUC Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 | Cycle 1 Day 1 and Day 5: pre-infusion, at 15 min during the infusion, at the end of infusion, and at 1, 1.5, 2, 4, 8, and 12 h post infusion | The AUC accumulation ratio of moxetumomab pasudotox was calculated as the geometric mean ratio of AUC(0-last) on the last day and the first day of a multiple dose regimen: Day 5/Day 1. |
| Number of Participants With Dose Limiting Toxicities (DLTs) | Cycle 1 Day 1 to Cycle 2 Day 10 (each cycle duration was 28 days) | Adverse events are suspected of causal relationship to drug and are \>=Grade (G) 3 in severity considered DLTs: G 3 or 4 hematologic abnormalities at baseline due to disease were not evaluable for hematologic DLT, G 2 allergic reactions of bronchospasm or urticaria, or any \>= G3 allergic reaction, in presence of pre-medication were considered DLTs. Following \>= G 3 non-hematological treatment-related toxicities not considered DLTs: Tumor lysis syndrome, G 3 low electrolyte levels with pre-existing low levels of same electrolytes, anticoagulant therapy, G 3 or 4 infection or neutropenic fever unless relationship to IP is suspected, G 3 transaminase, alkaline phosphatase, bilirubin or other liver function test elevation provided resolution to values required for study entry prior to start of next cycle, G 3 fever, G 3 hypertriglyceridemia and hypercholesterolemia, and G 4 hypertriglyceridemia lasting \<2 months, G 3 hypoalbuminemia lasting \<7 days occurred in absence of CLS. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years) | The TEAEs are defined as adverse events (AEs) present at baseline that worsened in intensity after administration of investigational product or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received moxetumomab pasudotox. |
| Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years) | Vital signs abnormalities reported as TEAEs included pyrexia, weight increased, dyspnoea, hypoxia, hypertension, hypotension. |
| Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years) | Cardiac AEs observed in participants with clinically significant ECG abnormalities included; ECG QT prolonged, Sinus tachycardia and Atrioventricular block first degree. |
| Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years) | An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. |
| Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR) | From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years) | Objective response rate defined as proportion of participants with confirmed CR or confirmed PR according to Response Evaluation Criteria for hairy cell leukemia (HCL). A CR is defined as: No evidence of leukemic cells by routine H/E stains of peripheral blood and bone marrow. No hepatomegaly, splenomegaly, or lymphadenopathy by physical examination and/or appropriate radiographic techniques. Normal complete blood count as: Neutrophils \>= 1,500/mcL, Platelets \>= 100,000/mcL, and Hemoglobin \>= 11.0 gm/dL without transfusions or growth factors for at least 4 weeks. Partial response requires all of following: \>=50% reduction in peripheral blood lymphocyte from pretreatment baseline value, lymphadenopathy, and abnormal hepatosplenomegaly by CT scan or physical exam, and complete blood count as Neutrophils \>= 1,500/mcL, Platelets \>=100,000/mcL, and Hemoglobin \>= 11.0 g/dL or 50% improvement of all parameters over baseline without transfusions or growth factors for at least 4 weeks. |
| Number of Participants With Complete Response (CR) | From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years) | The CR is defined by: No evidence of leukemic cells by routine H/E stains of the peripheral blood and bone marrow. No hepatomegaly, splenomegaly, or lymphadenopathy by physical examination and/or appropriate radiographic techniques. Normal complete blood count as exhibited by: Neutrophils \>= 1,500/microliter (mcL), Platelets \>= 100,000/mcL, and Hemoglobin \>= 11.0 gram per deciliter (gm/dL) without transfusions or growth factors for at least 4 weeks. |
| Number of Participants With Partial Response (PR) | From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years) | Partial response requires all of the following: \>=50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value, \>=50% reduction in lymphadenopathy, \>=50% reduction in abnormal hepatosplenomegaly by computed tomography or physical exam, Neutrophils \>= 1,500/mcL or 50% improvement over baseline without growth factors for at least 4 weeks, Platelets \>=100,000/mcL or 50% improvement over baseline, and Hemoglobin \>= 11.0 g/dL or 50% improvement over baseline without transfusions or growth factors for at least 4 weeks. For participants who are transfusion-dependent at baseline, a hemoglobin of \>= 9.0 g/dL without transfusions or growth factors for at least 4 weeks. |
| Number of Participants With Stable Disease (SD) | From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years) | Stable disease was characterized by not meeting the criteria for CR, PR or PD. |
| Number of Participants With Progressive Disease (PD) | From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years) | Progressive disease is defined by at least one of the following compared to pretreatment:\>= 25% increase in the sum of the products of the greatest perpendicular dimensions of at least two lymph nodes on two consecutive examinations at least 2 weeks apart (at least 1 node must be \>= 2 cm) or appearance of new palpable lymph nodes, \>=25% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, or appearance of new palpable hepatomegaly or splenomegaly that was not previously present, \>=50% increase in the absolute number of circulating lymphocytes, \>=25% decrease in hemoglobin (must be \< 11g/dL), platelets (must be \< 100,000/mcL), or absolute neutrophil count (must be \< 1500/mcL) unless these are judged to be effects of treatment. |
| Time to Complete Response | From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years) | Time to complete response (CR) was measured from the start of moxetumomab pasudotox treatment to the first documentation of CR and was evaluated only in participants who received any treatment of moxetumomab pasudotox and had achieved a CR. Time to complete response was summarized using Kaplan-Meier estimates (median time, 95% confidence interval \[CI\] for median time). |
| Time to Objective Response | From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years) | Time to OR was measured from the start of moxetumomab pasudotox treatment to the first documentation of OR and was evaluated only in participants who received any treatment of moxetumomab pasudotox and had achieved an OR (CR or PR). Objective response (OR) was defined as the participants with confirmed CR or confirmed PR according to Response Evaluation Criteria. |
| Duration of Complete Response | From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years) | Duration of CR was measured from the first documentation of CR to the first documented non-CR and was evaluated in participants who had achieved an CR. Duration of CR were summarized using Kaplan-Meier estimates (median time, 95% CI for median time). |
| Duration of Objective Response | From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years) | Duration of response was measured from the first documentation of objective response (OR) to the first documented non-response of SD, PD, or relapse and was only evaluated in participants who had achieved an OR (CR or PR). Duration of OR was summarized using Kaplan-Meier estimates (median time, 95% CI for median time). |
| Time to Progression | From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years) | Time to disease progression/relapse is measured from the start of moxetumomab pasudotox treatment until the first documentation of disease progression or relapse and was summarized using Kaplan-Meier estimates (median time, 95% CI for median time). |
| Progression-free Survival (PFS) | From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years) | PFS was measured from the start of moxetumomab pasudotox treatment until the first documentation of disease progression/relapse or death, whichever occurred first. PFS was summarized using Kaplan-Meier estimates (median time, 95% CI for median time). |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | Cycle 1 Day 1: pre-infusion; at 15 minutes (min) during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 hours (h) post infusion | The Tmax is the time to reach maximum observed plasma concentration of Moxetumomab Pasudotox. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion | The Tmax is the time to reach maximum observed plasma concentration of Moxetumomab Pasudotox. |
| Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 1 | Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion | The Cmax is the maximum observed plasma concentration of Moxetumomab Pasudotox. |
| Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 5 | Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion | The Cmax is the maximum observed plasma concentration of Moxetumomab Pasudotox. |
| Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion | The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time. |
| Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion | The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time. |
| Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion | Systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by area under plasma concentration-time curve from time zero to infinite time (AUC\[0-infinity\]). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CD22 Expression Levels From Peripheral Blood by Best Response | Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years) | Participants malignant cells (peripheral blood) were tested for cluster of differentiation 22 (CD22) expression by fluorescence-activated cell sorter (FACS) analysis. |
| CD22 Expression Levels From Bone Marrow by Best Response | Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years) | Participants malignant cells (paraffin block biopsy specimen) were tested for CD22 expression by FACS analysis. |
| Soluble CD22 Levels by Best Response | Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years) | Soluble CD22 was collected from the participant's plasma and was performed at the NCI using an ELISA method. |
| Number of Participants With Positive Neutralizing Antibodies and Correlation to Antitumor Activity | Up to end of treatment (approximately 8 years) | Participants tested for immunogenicity to moxetumomab pasudotox prior to enrollment, before each cycle and at end of study. The neutralization assay measures the capacity of participant's plasma (antibodies) to inhibit the binding of moxetumomab pasudotox to its target, cluster of differentiation 22 (CD22), coated onto enzyme linked immunosorbent assay (ELISA) plates. Significant level of neutralizing antibody activity defined as the capacity of test plasma to inhibit \>50% of the binding of CAT-8015 to CD22 using an ELISA-based method. |
Countries
Poland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 5 mcg/kg Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. | 3 |
| 10 mcg/kg Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. | 3 |
| 20 mcg/kg Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. | 3 |
| 30 mcg/kg Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. | 3 |
| 40 mcg/kg Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. | 4 |
| 50 mcg/kg Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. | 33 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse event/serious adverse event | 0 | 0 | 0 | 1 | 0 | 2 |
| Overall Study | Complete response | 0 | 1 | 0 | 0 | 2 | 2 |
| Overall Study | Development of neutralizing antibodies | 2 | 2 | 2 | 0 | 0 | 22 |
| Overall Study | Disease progression | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Initiation of alternative cancer therapy | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Other | 1 | 0 | 1 | 1 | 1 | 6 |
Baseline characteristics
| Characteristic | 5 mcg/kg | 10 mcg/kg | 20 mcg/kg | 30 mcg/kg | 40 mcg/kg | 50 mcg/kg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous Years | 56.3 Years STANDARD_DEVIATION 14.2 | 54.3 Years STANDARD_DEVIATION 6.1 | 56.3 Years STANDARD_DEVIATION 3.1 | 58.3 Years STANDARD_DEVIATION 4 | 61.8 Years STANDARD_DEVIATION 11.1 | 55.8 Years STANDARD_DEVIATION 9 | 56.4 Years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 28 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 4 | 33 / 33 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 2 / 3 | 0 / 4 | 4 / 33 |
Outcome results
Primary
Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 1
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
Time frame: Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
Population: The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The Overall Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mcg/kg | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 113 nanogram*hour per milliliter (ng*h/mL) | — |
| 10 mcg/kg | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 31.0 nanogram*hour per milliliter (ng*h/mL) | Standard Deviation 20.9 |
| 20 mcg/kg | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 109 nanogram*hour per milliliter (ng*h/mL) | — |
| 30 mcg/kg | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 897 nanogram*hour per milliliter (ng*h/mL) | — |
| 40 mcg/kg | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 183 nanogram*hour per milliliter (ng*h/mL) | Standard Deviation 146 |
| 50 mcg/kg | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 558 nanogram*hour per milliliter (ng*h/mL) | Standard Deviation 590 |
Primary
Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 5
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
Time frame: Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
Population: The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The Overall Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mcg/kg | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 179 ng*h/mL | Standard Deviation 155 |
| 10 mcg/kg | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 90.2 ng*h/mL | Standard Deviation 52.3 |
| 20 mcg/kg | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 93.2 ng*h/mL | Standard Deviation 113 |
| 30 mcg/kg | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 1360 ng*h/mL | — |
| 40 mcg/kg | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 1640 ng*h/mL | Standard Deviation 1270 |
| 50 mcg/kg | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 1920 ng*h/mL | Standard Deviation 1290 |
Primary
AUC Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1
The AUC accumulation ratio of moxetumomab pasudotox was calculated as the geometric mean ratio of AUC(0-last) on the last day and the first day of a multiple dose regimen: Day 5/Day 1.
Time frame: Cycle 1 Day 1 and Day 5: pre-infusion, at 15 min during the infusion, at the end of infusion, and at 1, 1.5, 2, 4, 8, and 12 h post infusion
Population: The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The Overall Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 5 mcg/kg | AUC Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 | 2.62 ratio |
| 10 mcg/kg | AUC Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 | 3.08 ratio |
| 20 mcg/kg | AUC Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 | 3.09 ratio |
| 30 mcg/kg | AUC Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 | 1.93 ratio |
| 40 mcg/kg | AUC Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 | 12.4 ratio |
| 50 mcg/kg | AUC Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 | 3.63 ratio |
Primary
Cmax Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1
The Cmax accumulation ratio of moxetumomab pasudotox was calculated as the geometric mean ratio of Cmax on the last day and the first day of a multiple dose regimen: Day 5/Day 1.
Time frame: Cycle 1 Day 1 and Day 5: pre-infusion, at 15 min during the infusion, at the end of infusion, and at 1, 1.5, 2, 4, 8, and 12 h post infusion
Population: The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The Overall Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 5 mcg/kg | Cmax Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 | 1.11 ratio |
| 10 mcg/kg | Cmax Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 | 1.73 ratio |
| 20 mcg/kg | Cmax Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 | 2.12 ratio |
| 30 mcg/kg | Cmax Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 | 1.48 ratio |
| 40 mcg/kg | Cmax Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 | 2.51 ratio |
| 50 mcg/kg | Cmax Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 | 1.58 ratio |
Primary
Duration of Complete Response
Duration of CR was measured from the first documentation of CR to the first documented non-CR and was evaluated in participants who had achieved an CR. Duration of CR were summarized using Kaplan-Meier estimates (median time, 95% CI for median time).
Time frame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox. Here, the Overall Number of Participants Analyzed denotes the number of participants who had achieved CR and had the first documented non-CR till end of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 10 mcg/kg | Duration of Complete Response | NA months |
| 20 mcg/kg | Duration of Complete Response | 25.89 months |
| 30 mcg/kg | Duration of Complete Response | 70.34 months |
| 50 mcg/kg | Duration of Complete Response | 42.35 months |
Primary
Duration of Objective Response
Duration of response was measured from the first documentation of objective response (OR) to the first documented non-response of SD, PD, or relapse and was only evaluated in participants who had achieved an OR (CR or PR). Duration of OR was summarized using Kaplan-Meier estimates (median time, 95% CI for median time).
Time frame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox. Here, the Overall Number of Participants Analyzed denotes the number of participants who had achieved an OR (CR or PR) and had the first documented non-response of SD, PD, or relapse.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 5 mcg/kg | Duration of Objective Response | 8.34 months |
| 10 mcg/kg | Duration of Objective Response | 84.44 months |
| 20 mcg/kg | Duration of Objective Response | 80.95 months |
| 30 mcg/kg | Duration of Objective Response | 78.29 months |
| 50 mcg/kg | Duration of Objective Response | NA months |
Primary
Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 1
The Cmax is the maximum observed plasma concentration of Moxetumomab Pasudotox.
Time frame: Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
Population: The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The Overall Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mcg/kg | Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 1 | 77.5 nanogram per milliliter (ng/mL) | Standard Deviation 70 |
| 10 mcg/kg | Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 1 | 86.3 nanogram per milliliter (ng/mL) | Standard Deviation 41.9 |
| 20 mcg/kg | Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 1 | 49.4 nanogram per milliliter (ng/mL) | Standard Deviation 46.3 |
| 30 mcg/kg | Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 1 | 443 nanogram per milliliter (ng/mL) | — |
| 40 mcg/kg | Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 1 | 290 nanogram per milliliter (ng/mL) | Standard Deviation 107 |
| 50 mcg/kg | Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 1 | 435 nanogram per milliliter (ng/mL) | Standard Deviation 260 |
Primary
Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 5
The Cmax is the maximum observed plasma concentration of Moxetumomab Pasudotox.
Time frame: Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
Population: The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The Overall Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mcg/kg | Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 5 | 103 ng/mL | Standard Deviation 40.5 |
| 10 mcg/kg | Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 5 | 135 ng/mL | Standard Deviation 49.1 |
| 20 mcg/kg | Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 5 | 161 ng/mL | Standard Deviation 136 |
| 30 mcg/kg | Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 5 | 420 ng/mL | Standard Deviation 384 |
| 40 mcg/kg | Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 5 | 701 ng/mL | Standard Deviation 328 |
| 50 mcg/kg | Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 5 | 738 ng/mL | Standard Deviation 316 |
Primary
Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs)
Cardiac AEs observed in participants with clinically significant ECG abnormalities included; ECG QT prolonged, Sinus tachycardia and Atrioventricular block first degree.
Time frame: From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 5 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | Sinus tachycardia | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | Atrioventricular block first degree | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | ECG QT prolonged | 1 Participants |
| 10 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | Sinus tachycardia | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | Atrioventricular block first degree | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | ECG QT prolonged | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | Atrioventricular block first degree | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | ECG QT prolonged | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | Sinus tachycardia | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | ECG QT prolonged | 2 Participants |
| 30 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | Sinus tachycardia | 1 Participants |
| 30 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | Atrioventricular block first degree | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | Atrioventricular block first degree | 1 Participants |
| 40 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | ECG QT prolonged | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | Sinus tachycardia | 0 Participants |
| 50 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | Sinus tachycardia | 2 Participants |
| 50 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | ECG QT prolonged | 2 Participants |
| 50 mcg/kg | Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) | Atrioventricular block first degree | 0 Participants |
Primary
Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event.
Time frame: From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 2 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoglycaemia | 1 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypocalcaemia | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypernatraemia | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobin decreased | 2 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 2 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertriglyceridaemia | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperuricaemia | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 1 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil count decreased | 2 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Protein urine | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bicarbonate decreased | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Lymphocyte count decreased | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | White blood cell count decresed | 2 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bilirubin increased | 2 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Lymphopenia | 2 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatine phosphokinase increased | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Haptoglobin decreased | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperkalaemia | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypercholesterolaemia | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatinine increased | 1 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobinuria | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood triglycerides increased | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Platelet count decreased | 1 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Proteinuria | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobin urine | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Gamma-glutamyltransferase increased | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypophosphataemia | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood uric acid increased | 1 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyponatraemia | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypomagnesaemia | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperglycaemia | 2 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypokalaemia | 0 Participants |
| 5 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypermagnesaemia | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypermagnesaemia | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobin decreased | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypophosphataemia | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypocalcaemia | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypercholesterolaemia | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoglycaemia | 1 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypernatraemia | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyponatraemia | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 1 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatinine increased | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperuricaemia | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Platelet count decreased | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertriglyceridaemia | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil count decreased | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobinuria | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperglycaemia | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Proteinuria | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood uric acid increased | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood triglycerides increased | 1 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Lymphocyte count decreased | 1 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 1 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bicarbonate decreased | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 1 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Haptoglobin decreased | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | White blood cell count decresed | 1 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobin urine | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypomagnesaemia | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bilirubin increased | 1 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Protein urine | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Lymphopenia | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypokalaemia | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperkalaemia | 1 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Gamma-glutamyltransferase increased | 0 Participants |
| 10 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatine phosphokinase increased | 1 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Lymphocyte count decreased | 1 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 1 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 1 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bicarbonate decreased | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bilirubin increased | 1 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatine phosphokinase increased | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatinine increased | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood triglycerides increased | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Gamma-glutamyltransferase increased | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood uric acid increased | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperglycaemia | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypermagnesaemia | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypernatraemia | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertriglyceridaemia | 1 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperuricaemia | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 1 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypocalcaemia | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoglycaemia | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypokalaemia | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypomagnesaemia | 1 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyponatraemia | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypophosphataemia | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobin urine | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Protein urine | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Proteinuria | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobinuria | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypercholesterolaemia | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperkalaemia | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Lymphopenia | 2 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | White blood cell count decresed | 2 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil count decreased | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobin decreased | 2 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Platelet count decreased | 0 Participants |
| 20 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Haptoglobin decreased | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 3 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Lymphopenia | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Protein urine | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperuricaemia | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bilirubin increased | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood triglycerides increased | 1 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperkalaemia | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 3 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Proteinuria | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Haptoglobin decreased | 1 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatine phosphokinase increased | 1 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypomagnesaemia | 1 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatinine increased | 1 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoglycaemia | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobinuria | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil count decreased | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypercholesterolaemia | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Platelet count decreased | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood uric acid increased | 1 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertriglyceridaemia | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobin decreased | 1 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyponatraemia | 2 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperglycaemia | 2 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 1 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 2 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Gamma-glutamyltransferase increased | 1 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypermagnesaemia | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypophosphataemia | 1 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypokalaemia | 2 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Lymphocyte count decreased | 2 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bicarbonate decreased | 0 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypocalcaemia | 1 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | White blood cell count decresed | 1 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobin urine | 1 Participants |
| 30 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypernatraemia | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobin decreased | 1 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 1 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoglycaemia | 1 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperglycaemia | 2 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypokalaemia | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood uric acid increased | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypomagnesaemia | 1 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyponatraemia | 3 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Gamma-glutamyltransferase increased | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypophosphataemia | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood triglycerides increased | 1 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobin urine | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Protein urine | 1 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 2 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Proteinuria | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatinine increased | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Haptoglobin decreased | 1 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobinuria | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatine phosphokinase increased | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypercholesterolaemia | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Platelet count decreased | 2 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperkalaemia | 1 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bilirubin increased | 1 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Lymphopenia | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bicarbonate decreased | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | White blood cell count decresed | 2 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Lymphocyte count decreased | 2 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertriglyceridaemia | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperuricaemia | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypernatraemia | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil count decreased | 0 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 3 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypermagnesaemia | 1 Participants |
| 40 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypocalcaemia | 1 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bicarbonate decreased | 5 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypokalaemia | 2 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobin urine | 0 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobin decreased | 9 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Neutrophil count decreased | 10 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | White blood cell count decresed | 17 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood triglycerides increased | 2 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood alkaline phosphatase increased | 5 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoglycaemia | 1 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypophosphataemia | 10 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperglycaemia | 13 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Lymphocyte count decreased | 5 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyponatraemia | 7 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 24 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Haptoglobin decreased | 7 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 25 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertriglyceridaemia | 19 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Gamma-glutamyltransferase increased | 7 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypernatraemia | 6 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatine phosphokinase increased | 4 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hemoglobinuria | 3 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypomagnesaemia | 7 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypercholesterolaemia | 9 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Proteinuria | 9 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood bilirubin increased | 2 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood uric acid increased | 1 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Blood creatinine increased | 11 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypermagnesaemia | 12 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperkalaemia | 5 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hyperuricaemia | 4 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Protein urine | 1 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Platelet count decreased | 6 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 25 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypocalcaemia | 11 Participants |
| 50 mcg/kg | Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Lymphopenia | 25 Participants |
Primary
Number of Participants With Complete Response (CR)
The CR is defined by: No evidence of leukemic cells by routine H/E stains of the peripheral blood and bone marrow. No hepatomegaly, splenomegaly, or lymphadenopathy by physical examination and/or appropriate radiographic techniques. Normal complete blood count as exhibited by: Neutrophils \>= 1,500/microliter (mcL), Platelets \>= 100,000/mcL, and Hemoglobin \>= 11.0 gram per deciliter (gm/dL) without transfusions or growth factors for at least 4 weeks.
Time frame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5 mcg/kg | Number of Participants With Complete Response (CR) | 0 Participants |
| 10 mcg/kg | Number of Participants With Complete Response (CR) | 2 Participants |
| 20 mcg/kg | Number of Participants With Complete Response (CR) | 2 Participants |
| 30 mcg/kg | Number of Participants With Complete Response (CR) | 1 Participants |
| 40 mcg/kg | Number of Participants With Complete Response (CR) | 2 Participants |
| 50 mcg/kg | Number of Participants With Complete Response (CR) | 21 Participants |
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
Adverse events are suspected of causal relationship to drug and are \>=Grade (G) 3 in severity considered DLTs: G 3 or 4 hematologic abnormalities at baseline due to disease were not evaluable for hematologic DLT, G 2 allergic reactions of bronchospasm or urticaria, or any \>= G3 allergic reaction, in presence of pre-medication were considered DLTs. Following \>= G 3 non-hematological treatment-related toxicities not considered DLTs: Tumor lysis syndrome, G 3 low electrolyte levels with pre-existing low levels of same electrolytes, anticoagulant therapy, G 3 or 4 infection or neutropenic fever unless relationship to IP is suspected, G 3 transaminase, alkaline phosphatase, bilirubin or other liver function test elevation provided resolution to values required for study entry prior to start of next cycle, G 3 fever, G 3 hypertriglyceridemia and hypercholesterolemia, and G 4 hypertriglyceridemia lasting \<2 months, G 3 hypoalbuminemia lasting \<7 days occurred in absence of CLS.
Time frame: Cycle 1 Day 1 to Cycle 2 Day 10 (each cycle duration was 28 days)
Population: Evaluable population for DLT included all participants who received any treatment of moxetumomab pasudotox, completed at least Cycle 2 Day 10, or discontinued treatment due to a DLT on or before Cycle 2 Day 10.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| 10 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| 20 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| 30 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| 40 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| 50 mcg/kg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Primary
Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR)
Objective response rate defined as proportion of participants with confirmed CR or confirmed PR according to Response Evaluation Criteria for hairy cell leukemia (HCL). A CR is defined as: No evidence of leukemic cells by routine H/E stains of peripheral blood and bone marrow. No hepatomegaly, splenomegaly, or lymphadenopathy by physical examination and/or appropriate radiographic techniques. Normal complete blood count as: Neutrophils \>= 1,500/mcL, Platelets \>= 100,000/mcL, and Hemoglobin \>= 11.0 gm/dL without transfusions or growth factors for at least 4 weeks. Partial response requires all of following: \>=50% reduction in peripheral blood lymphocyte from pretreatment baseline value, lymphadenopathy, and abnormal hepatosplenomegaly by CT scan or physical exam, and complete blood count as Neutrophils \>= 1,500/mcL, Platelets \>=100,000/mcL, and Hemoglobin \>= 11.0 g/dL or 50% improvement of all parameters over baseline without transfusions or growth factors for at least 4 weeks.
Time frame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5 mcg/kg | Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR) | 3 Participants |
| 10 mcg/kg | Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR) | 3 Participants |
| 20 mcg/kg | Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR) | 2 Participants |
| 30 mcg/kg | Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR) | 2 Participants |
| 40 mcg/kg | Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR) | 3 Participants |
| 50 mcg/kg | Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR) | 29 Participants |
Primary
Number of Participants With Partial Response (PR)
Partial response requires all of the following: \>=50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value, \>=50% reduction in lymphadenopathy, \>=50% reduction in abnormal hepatosplenomegaly by computed tomography or physical exam, Neutrophils \>= 1,500/mcL or 50% improvement over baseline without growth factors for at least 4 weeks, Platelets \>=100,000/mcL or 50% improvement over baseline, and Hemoglobin \>= 11.0 g/dL or 50% improvement over baseline without transfusions or growth factors for at least 4 weeks. For participants who are transfusion-dependent at baseline, a hemoglobin of \>= 9.0 g/dL without transfusions or growth factors for at least 4 weeks.
Time frame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5 mcg/kg | Number of Participants With Partial Response (PR) | 3 Participants |
| 10 mcg/kg | Number of Participants With Partial Response (PR) | 1 Participants |
| 20 mcg/kg | Number of Participants With Partial Response (PR) | 0 Participants |
| 30 mcg/kg | Number of Participants With Partial Response (PR) | 1 Participants |
| 40 mcg/kg | Number of Participants With Partial Response (PR) | 1 Participants |
| 50 mcg/kg | Number of Participants With Partial Response (PR) | 8 Participants |
Primary
Number of Participants With Progressive Disease (PD)
Progressive disease is defined by at least one of the following compared to pretreatment:\>= 25% increase in the sum of the products of the greatest perpendicular dimensions of at least two lymph nodes on two consecutive examinations at least 2 weeks apart (at least 1 node must be \>= 2 cm) or appearance of new palpable lymph nodes, \>=25% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, or appearance of new palpable hepatomegaly or splenomegaly that was not previously present, \>=50% increase in the absolute number of circulating lymphocytes, \>=25% decrease in hemoglobin (must be \< 11g/dL), platelets (must be \< 100,000/mcL), or absolute neutrophil count (must be \< 1500/mcL) unless these are judged to be effects of treatment.
Time frame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5 mcg/kg | Number of Participants With Progressive Disease (PD) | 0 Participants |
| 10 mcg/kg | Number of Participants With Progressive Disease (PD) | 0 Participants |
| 20 mcg/kg | Number of Participants With Progressive Disease (PD) | 0 Participants |
| 30 mcg/kg | Number of Participants With Progressive Disease (PD) | 0 Participants |
| 40 mcg/kg | Number of Participants With Progressive Disease (PD) | 1 Participants |
| 50 mcg/kg | Number of Participants With Progressive Disease (PD) | 0 Participants |
Primary
Number of Participants With Stable Disease (SD)
Stable disease was characterized by not meeting the criteria for CR, PR or PD.
Time frame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5 mcg/kg | Number of Participants With Stable Disease (SD) | 0 Participants |
| 10 mcg/kg | Number of Participants With Stable Disease (SD) | 0 Participants |
| 20 mcg/kg | Number of Participants With Stable Disease (SD) | 1 Participants |
| 30 mcg/kg | Number of Participants With Stable Disease (SD) | 1 Participants |
| 40 mcg/kg | Number of Participants With Stable Disease (SD) | 0 Participants |
| 50 mcg/kg | Number of Participants With Stable Disease (SD) | 4 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
The TEAEs are defined as adverse events (AEs) present at baseline that worsened in intensity after administration of investigational product or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received moxetumomab pasudotox.
Time frame: From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 5 mcg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 Participants |
| 5 mcg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| 10 mcg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 Participants |
| 10 mcg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| 20 mcg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 Participants |
| 20 mcg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| 30 mcg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 3 Participants |
| 30 mcg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 2 Participants |
| 40 mcg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 4 Participants |
| 40 mcg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 0 Participants |
| 50 mcg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 33 Participants |
| 50 mcg/kg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 4 Participants |
Primary
Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Vital signs abnormalities reported as TEAEs included pyrexia, weight increased, dyspnoea, hypoxia, hypertension, hypotension.
Time frame: From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 5 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Pyrexia | 1 Participants |
| 5 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Weight increased | 1 Participants |
| 5 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Dyspnoea | 1 Participants |
| 5 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoxia | 0 Participants |
| 5 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertension | 0 Participants |
| 5 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypotension | 0 Participants |
| 10 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Weight increased | 0 Participants |
| 10 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoxia | 0 Participants |
| 10 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypotension | 0 Participants |
| 10 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Pyrexia | 1 Participants |
| 10 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Dyspnoea | 0 Participants |
| 10 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertension | 1 Participants |
| 20 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypotension | 0 Participants |
| 20 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertension | 0 Participants |
| 20 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoxia | 0 Participants |
| 20 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Dyspnoea | 0 Participants |
| 20 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Pyrexia | 2 Participants |
| 20 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Weight increased | 0 Participants |
| 30 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoxia | 1 Participants |
| 30 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Weight increased | 0 Participants |
| 30 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Dyspnoea | 1 Participants |
| 30 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypotension | 2 Participants |
| 30 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertension | 1 Participants |
| 30 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Pyrexia | 3 Participants |
| 40 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Pyrexia | 1 Participants |
| 40 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertension | 0 Participants |
| 40 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Weight increased | 0 Participants |
| 40 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Dyspnoea | 0 Participants |
| 40 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoxia | 0 Participants |
| 40 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypotension | 0 Participants |
| 50 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypoxia | 1 Participants |
| 50 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Dyspnoea | 6 Participants |
| 50 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypertension | 0 Participants |
| 50 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Hypotension | 10 Participants |
| 50 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Weight increased | 6 Participants |
| 50 mcg/kg | Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) | Pyrexia | 16 Participants |
Primary
Progression-free Survival (PFS)
PFS was measured from the start of moxetumomab pasudotox treatment until the first documentation of disease progression/relapse or death, whichever occurred first. PFS was summarized using Kaplan-Meier estimates (median time, 95% CI for median time).
Time frame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 5 mcg/kg | Progression-free Survival (PFS) | 11.33 months |
| 10 mcg/kg | Progression-free Survival (PFS) | NA months |
| 20 mcg/kg | Progression-free Survival (PFS) | NA months |
| 30 mcg/kg | Progression-free Survival (PFS) | 82.07 months |
| 40 mcg/kg | Progression-free Survival (PFS) | NA months |
| 50 mcg/kg | Progression-free Survival (PFS) | NA months |
Primary
Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 1
Systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by area under plasma concentration-time curve from time zero to infinite time (AUC\[0-infinity\]).
Time frame: Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
Population: The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The Overall Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mcg/kg | Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 32.6 Milliliter/kilogram/hour (mL/kg/h) | — |
| 20 mcg/kg | Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 49.1 Milliliter/kilogram/hour (mL/kg/h) | — |
| 30 mcg/kg | Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 43.9 Milliliter/kilogram/hour (mL/kg/h) | — |
| 40 mcg/kg | Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 91.8 Milliliter/kilogram/hour (mL/kg/h) | — |
| 50 mcg/kg | Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 106 Milliliter/kilogram/hour (mL/kg/h) | Standard Deviation 80.2 |
Primary
Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 5
Systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by AUC(0-infinity).
Time frame: Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
Population: The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The Overall Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mcg/kg | Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 13.3 mL/kg/h | — |
| 10 mcg/kg | Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 68.9 mL/kg/h | — |
| 20 mcg/kg | Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 66.3 mL/kg/h | — |
| 30 mcg/kg | Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 18.7 mL/kg/h | — |
| 40 mcg/kg | Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 45.5 mL/kg/h | Standard Deviation 47.6 |
| 50 mcg/kg | Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 33.3 mL/kg/h | Standard Deviation 37.5 |
Primary
Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 1
The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Time frame: Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
Population: The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The Overall Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mcg/kg | Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 0.643 hours | — |
| 20 mcg/kg | Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 3.77 hours | — |
| 30 mcg/kg | Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 1.00 hours | — |
| 40 mcg/kg | Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 0.375 hours | — |
| 50 mcg/kg | Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 0.799 hours | Standard Deviation 0.755 |
Primary
Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 5
The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Time frame: Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
Population: The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The Overall Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mcg/kg | Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 2.20 hours | — |
| 10 mcg/kg | Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 0.369 hours | — |
| 20 mcg/kg | Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 0.404 hours | — |
| 30 mcg/kg | Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 1.86 hours | — |
| 40 mcg/kg | Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 1.66 hours | Standard Deviation 0.928 |
| 50 mcg/kg | Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 2.06 hours | Standard Deviation 0.98 |
Primary
Time to Complete Response
Time to complete response (CR) was measured from the start of moxetumomab pasudotox treatment to the first documentation of CR and was evaluated only in participants who received any treatment of moxetumomab pasudotox and had achieved a CR. Time to complete response was summarized using Kaplan-Meier estimates (median time, 95% confidence interval \[CI\] for median time).
Time frame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox. The Overall Number of Participants Analyzed denotes the number of participants who had achieved a CR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 10 mcg/kg | Time to Complete Response | 2.53 months |
| 20 mcg/kg | Time to Complete Response | 9.56 months |
| 30 mcg/kg | Time to Complete Response | 3.71 months |
| 40 mcg/kg | Time to Complete Response | 2.53 months |
| 50 mcg/kg | Time to Complete Response | 3.94 months |
Primary
Time to Objective Response
Time to OR was measured from the start of moxetumomab pasudotox treatment to the first documentation of OR and was evaluated only in participants who received any treatment of moxetumomab pasudotox and had achieved an OR (CR or PR). Objective response (OR) was defined as the participants with confirmed CR or confirmed PR according to Response Evaluation Criteria.
Time frame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox. The Overall Number of Participants Analyzed denotes the number of participants who had achieved an OR (CR or PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 5 mcg/kg | Time to Objective Response | 3.02 months |
| 10 mcg/kg | Time to Objective Response | 1.12 months |
| 20 mcg/kg | Time to Objective Response | 8.2 months |
| 30 mcg/kg | Time to Objective Response | 8.18 months |
| 40 mcg/kg | Time to Objective Response | 1.08 months |
| 50 mcg/kg | Time to Objective Response | 1.05 months |
Primary
Time to Progression
Time to disease progression/relapse is measured from the start of moxetumomab pasudotox treatment until the first documentation of disease progression or relapse and was summarized using Kaplan-Meier estimates (median time, 95% CI for median time).
Time frame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 5 mcg/kg | Time to Progression | 11.33 months |
| 10 mcg/kg | Time to Progression | NA months |
| 20 mcg/kg | Time to Progression | NA months |
| 30 mcg/kg | Time to Progression | 82.07 months |
| 40 mcg/kg | Time to Progression | NA months |
| 50 mcg/kg | Time to Progression | NA months |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 1
The Tmax is the time to reach maximum observed plasma concentration of Moxetumomab Pasudotox.
Time frame: Cycle 1 Day 1: pre-infusion; at 15 minutes (min) during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 hours (h) post infusion
Population: The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The Overall Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 5 mcg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 0.508 hours |
| 10 mcg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 0.467 hours |
| 20 mcg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 0.367 hours |
| 30 mcg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 0.467 hours |
| 40 mcg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 0.267 hours |
| 50 mcg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 1 | 0.417 hours |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 5
The Tmax is the time to reach maximum observed plasma concentration of Moxetumomab Pasudotox.
Time frame: Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
Population: The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The Overall Number of Participants Analyzed denotes the number of participants evaluated for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 5 mcg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 0.500 hours |
| 10 mcg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 0.467 hours |
| 20 mcg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 0.250 hours |
| 30 mcg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 0.517 hours |
| 40 mcg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 0.475 hours |
| 50 mcg/kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 5 | 0.417 hours |
Secondary
CD22 Expression Levels From Bone Marrow by Best Response
Participants malignant cells (paraffin block biopsy specimen) were tested for CD22 expression by FACS analysis.
Time frame: Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mcg/kg | CD22 Expression Levels From Bone Marrow by Best Response | Bone Marrow: Partial Response | 36286.0 sites per cell | — |
| 10 mcg/kg | CD22 Expression Levels From Bone Marrow by Best Response | Bone Marrow: Complete Response | 75157.0 sites per cell | — |
| 30 mcg/kg | CD22 Expression Levels From Bone Marrow by Best Response | Bone Marrow: Complete Response | 50190.0 sites per cell | — |
| 30 mcg/kg | CD22 Expression Levels From Bone Marrow by Best Response | Bone Marrow: Stable Disease | 80400.0 sites per cell | — |
| 50 mcg/kg | CD22 Expression Levels From Bone Marrow by Best Response | Bone Marrow: Complete Response | 55850.5 sites per cell | Standard Deviation 18482.2 |
| 50 mcg/kg | CD22 Expression Levels From Bone Marrow by Best Response | Bone Marrow: Partial Response | 37732.5 sites per cell | Standard Deviation 9918.6 |
| 50 mcg/kg | CD22 Expression Levels From Bone Marrow by Best Response | Bone Marrow: Stable Disease | 36767.5 sites per cell | Standard Deviation 720.5 |
Secondary
CD22 Expression Levels From Peripheral Blood by Best Response
Participants malignant cells (peripheral blood) were tested for cluster of differentiation 22 (CD22) expression by fluorescence-activated cell sorter (FACS) analysis.
Time frame: Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mcg/kg | CD22 Expression Levels From Peripheral Blood by Best Response | Peripheral Blood: Partial Response | 38402.7 sites per cell | Standard Deviation 14131.9 |
| 10 mcg/kg | CD22 Expression Levels From Peripheral Blood by Best Response | Peripheral Blood: Partial Response | 78356.0 sites per cell | — |
| 10 mcg/kg | CD22 Expression Levels From Peripheral Blood by Best Response | Peripheral Blood: Complete Response | 65434.0 sites per cell | — |
| 20 mcg/kg | CD22 Expression Levels From Peripheral Blood by Best Response | Peripheral Blood: Stable Disease | 38939.0 sites per cell | — |
| 20 mcg/kg | CD22 Expression Levels From Peripheral Blood by Best Response | Peripheral Blood: Complete Response | 72632.0 sites per cell | Standard Deviation 12010.9 |
| 30 mcg/kg | CD22 Expression Levels From Peripheral Blood by Best Response | Peripheral Blood: Complete Response | 43803.0 sites per cell | — |
| 30 mcg/kg | CD22 Expression Levels From Peripheral Blood by Best Response | Peripheral Blood: Stable Disease | 84157.0 sites per cell | — |
| 30 mcg/kg | CD22 Expression Levels From Peripheral Blood by Best Response | Peripheral Blood: Partial Response | 76264.0 sites per cell | — |
| 40 mcg/kg | CD22 Expression Levels From Peripheral Blood by Best Response | Peripheral Blood: ProgressiveDisease | 24645.0 sites per cell | — |
| 40 mcg/kg | CD22 Expression Levels From Peripheral Blood by Best Response | Peripheral Blood: Complete Response | 61773.0 sites per cell | — |
| 40 mcg/kg | CD22 Expression Levels From Peripheral Blood by Best Response | Peripheral Blood: Partial Response | 52495.0 sites per cell | — |
| 50 mcg/kg | CD22 Expression Levels From Peripheral Blood by Best Response | Peripheral Blood: Partial Response | 33259.9 sites per cell | Standard Deviation 25479.5 |
| 50 mcg/kg | CD22 Expression Levels From Peripheral Blood by Best Response | Peripheral Blood: Stable Disease | 46089.3 sites per cell | Standard Deviation 9644.6 |
| 50 mcg/kg | CD22 Expression Levels From Peripheral Blood by Best Response | Peripheral Blood: Complete Response | 68141.3 sites per cell | Standard Deviation 13614 |
Secondary
Number of Participants With Positive Neutralizing Antibodies and Correlation to Antitumor Activity
Participants tested for immunogenicity to moxetumomab pasudotox prior to enrollment, before each cycle and at end of study. The neutralization assay measures the capacity of participant's plasma (antibodies) to inhibit the binding of moxetumomab pasudotox to its target, cluster of differentiation 22 (CD22), coated onto enzyme linked immunosorbent assay (ELISA) plates. Significant level of neutralizing antibody activity defined as the capacity of test plasma to inhibit \>50% of the binding of CAT-8015 to CD22 using an ELISA-based method.
Time frame: Up to end of treatment (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 5 mcg/kg | Number of Participants With Positive Neutralizing Antibodies and Correlation to Antitumor Activity | 2 Participants |
| 10 mcg/kg | Number of Participants With Positive Neutralizing Antibodies and Correlation to Antitumor Activity | 2 Participants |
| 20 mcg/kg | Number of Participants With Positive Neutralizing Antibodies and Correlation to Antitumor Activity | 2 Participants |
| 30 mcg/kg | Number of Participants With Positive Neutralizing Antibodies and Correlation to Antitumor Activity | 1 Participants |
| 40 mcg/kg | Number of Participants With Positive Neutralizing Antibodies and Correlation to Antitumor Activity | 0 Participants |
| 50 mcg/kg | Number of Participants With Positive Neutralizing Antibodies and Correlation to Antitumor Activity | 7 Participants |
Secondary
Soluble CD22 Levels by Best Response
Soluble CD22 was collected from the participant's plasma and was performed at the NCI using an ELISA method.
Time frame: Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years)
Population: Safety population included all participants who received any treatment of moxetumomab pasudotox.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mcg/kg | Soluble CD22 Levels by Best Response | Partial Response | 3016.3 picogram/mL | Standard Deviation 1821.3 |
| 10 mcg/kg | Soluble CD22 Levels by Best Response | Partial Response | 16675.0 picogram/mL | — |
| 10 mcg/kg | Soluble CD22 Levels by Best Response | Complete Response | 2583.0 picogram/mL | — |
| 20 mcg/kg | Soluble CD22 Levels by Best Response | Complete Response | 60021.0 picogram/mL | — |
| 20 mcg/kg | Soluble CD22 Levels by Best Response | Stable Disease | 184750.0 picogram/mL | Standard Deviation 21566.8 |
| 30 mcg/kg | Soluble CD22 Levels by Best Response | Partial Response | 5122.0 picogram/mL | — |
| 30 mcg/kg | Soluble CD22 Levels by Best Response | Complete Response | 5109.0 picogram/mL | — |
| 30 mcg/kg | Soluble CD22 Levels by Best Response | Stable Disease | 528000.0 picogram/mL | — |
| 40 mcg/kg | Soluble CD22 Levels by Best Response | Partial Response | 18238.5 picogram/mL | Standard Deviation 45.5 |
| 40 mcg/kg | Soluble CD22 Levels by Best Response | Complete Response | 10232.0 picogram/mL | — |
| 40 mcg/kg | Soluble CD22 Levels by Best Response | Progressive Disease | 7484.0 picogram/mL | — |
| 50 mcg/kg | Soluble CD22 Levels by Best Response | Partial Response | 39493.5 picogram/mL | Standard Deviation 31216.9 |
| 50 mcg/kg | Soluble CD22 Levels by Best Response | Stable Disease | 134129.5 picogram/mL | Standard Deviation 150498.4 |
| 50 mcg/kg | Soluble CD22 Levels by Best Response | Complete Response | 22202.9 picogram/mL | Standard Deviation 27809.4 |