High-risk Diffuse Large B-Cell Lymphoma
Conditions
Brief summary
A phase 2, multicenter, open-label, single arm clinical trial in adults with newly diagnosed aggressive high-risk DLBCL.
Detailed description
The safety profile of blinatumomab after frontline rituximab (R)-chemotherapy, consisting of either R-CHOP (14 or 21) (rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone) or R-DA-EPOCH (rituximab and dose adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), or R-CHOEP (rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide), will be determined. The study will consist of a screening period of up to 14 days, a standard of care (SOC) R-chemotherapy run-in period of approximately 21 weeks, a 12 to 16 week blinatumomab treatment period, a 30-day safety follow-up visit, and a long-term follow-up period that begins after the safety follow-up visit is completed until 1 year from the first dose blinatumomab.
Interventions
DRUGBlinatumomab
Blinatumomab monotherapy was supplied in single-use sterile glass injection vials and administered as an IV infusion.
During the run-in period participants received 6 cycles of standard of care rituximab-chemotherapy dosed per investigator's institution standard as follows: * R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine,prednisone) * R-DA-EPOCH (rituximab and dose adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) or * R-CHOEP (rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide).
DRUGDexamethasone
Dexamethasone 20 mg IV: within 1 hour prior to start of treatment in each treatment cycle, and within 1 hour prior to dose-step (increase).
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Subject has provided informed consent prior to initiation of any study-specific activities/procedures * Age ≥ 18 at time of informed consent * Subject must have untreated histologically proven high-risk DLBCL defined by atleast one of the following: * International Prognostic Index (IPI) for Diffuse Large B-cell Lymphoma 3 to 5 (representing high intermedidate - high ratings), * Double-hit or higher or double protein expression * Eastern Cooperative Oncology Group performance status ≤ 2. * Subject meets the criteria per investigator's institution to receive standard of care (SOC) rituximab-chemotherapy (ie, R-CHOP \[14 or 21\] or R-DA-EPOCH or R-CHOEP) of 6 cycles. Subjects may be enrolled on study prior to cycle 1 or cycle 2 of SOC R-chemotherapy * Adequate organ and bone marrow function determined within 14 days prior to enrollment defined as: * Hematological: Absolute neutrophil count ≥1\*10\^9/L; Platelet count ≥75\*10\^9/L;Hemoglobin ≥8g/dL * Renal: Creatinine clearance ≥50mL/min; * Hepatic: Aspartate aminotransferase/Alanine aminotransferase \<3\*upper limit of normal (ULN); Total bilirubin \<2\*ULN (unless Gilbert's Disease or if liver involvement with lymphoma) * Subject must have completed 6 cycles of SOC R-chemotherapy and achieved CR, PR or stable disease by PET/CT performed 3 weeks (± 3 days) after cycle 6 of SOC R-chemotherapy. Subjects with progressive disease (PD) are not eligible for treatment with blinatumomab and will end the study.
Exclusion criteria
* Clinically relevant central nervous system (CNS) pathology requiring treatment such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis * Evidence of CNS involvement with DLBCL at disease evaluation obtained prior to starting blinatumomab * Current autoimmune disease or history of autoimmune disease with potential of CNS involvement * Subject has active infection requiring systemic therapy * Prior anti-CD19 therapies * Known infection with HIV or chronic infection with hepatitis B virus or hepatitis C virus * History of other malignancy within the past 3 years with the following exceptions: * Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician * Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease * Adequately treated cervical carcinoma in situ without evidence of disease * Adequately treated breast ductal carcinoma in situ without evidence of disease * Prostatic intraepithelial neoplasia without evidence of prostate cancer * Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ * Subject has known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing. * Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge. * History/evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. * Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed while receiving blinatumomab and for an additional 48 hours after the last treatment dose of blinatumomab. * Currently receiving treatment in another investigational device or drug study or less than 30 days since ending treatment on another investigational device or drug study. Other investigational procedures while participating in this study are excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Treatment-Emergent (Blinatumomab) Adverse Events | From the start of first infusion of IP to 30 days after the end of last infusion of IP; median (min, max) treatment duration was 56 (16, 84) days | Overall incidence and severity of treatment-emergent adverse events occurring during the blinatumomab investigative product (IP) treatment period graded by investigators according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and based on the scale: Grade 1 = Mild - transient or mild discomfort; Grade 2 = Moderate - mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required; Grade 3 = Severe - marked limitation in activity, assistance usually required; medical intervention required, hospitalization is possible; Grade 4 = Life threatening - extreme limitation in activity, assistance required; medical intervention, hospitalization or hospice care probable; Grade 5 = death. |
| Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment | From the start of first infusion of IP to 30 days after the end of last infusion of IP; median (min, max) treatment duration was 56 (16, 84) days | Overall incidence and severity of treatment-emergent adverse events deemed by investigators to be related to blinatumomab treatment. Severity was graded by investigators according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and based on the scale: Grade 1 = Mild - transient or mild discomfort; Grade 2 = Moderate - mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required; Grade 3 = Severe - marked limitation in activity, assistance usually required; medical intervention required, hospitalization is possible; Grade 4 = Life threatening - extreme limitation in activity, assistance required; medical intervention, hospitalization or hospice care probable; Grade 5 = death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period | Cycle 1: Day 78 (3 weeks following end of Cycle 1 IP treatment) Treatment Period: Either the Cycle 1 timeframe or approximately Day 128 (3 weeks after Cycle 2 ended) for participants who completed Cycle 2 | Tumor response assessment was performed by a central reader according to modified Lugano classification using PET/CT scan. CMR: a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with/without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. |
| Kaplan-Meier Estimates for Overall Survival (OS) From First Dose of Blinatumomab | The median (range) follow-up time was 12.0 (10.7, 14.5) months. | OS was calculated as the time from the date of first IP infusion until death due to any cause. Participants who are alive at the date that triggers the analysis were censored at the date last known to be alive. Months were calculated as days from the first dose date of blinatumomab to death/censor date, divided by 30.5. |
| Kaplan-Meier Estimates for Progression Free Survival (PFS) From First Dose of Blinatumomab | The median (range) follow-up time was 12.0 (8.2, 14.5) | PFS was calculated as the time from the date of first IP infusion until the date of diagnosis of progression of DLBCL or the date of death, whichever was the earliest. The diagnosis of progression of DLBCL was defined as the first diagnosis of progressive metabolic response/progressive disease based on PET/CT scan per central or investigator review during the treatment period or relapse based on clinical tumor assessment during the long-term follow up period. Participants who were alive and did not have progression were censored at the last evaluable non-missing tumor assessment date prior to the analysis trigger date. |
| Overall Objective Response Rate (ORR) Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) and Partial Metabolic Response (PMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period | Cycle 1: Day 78 (3 weeks following end of Cycle 1 IP treatment) Treatment Period: Either the Cycle 1 timeframe or approximately Day 128 (3 weeks after Cycle 2 ended) for participants who completed Cycle 2 | Tumor response assessment was performed by a central reader according to modified Lugano classification using PET/CT scan. Overall objective response rate (ORR) is the percentage of participants with a best overall response of complete metabolic response (CMR) or partial metabolic response (PMR). CMR: a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with/without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PMR: a score 4 (uptake moderately greater than \[\>\] liver) or 5 (uptake markedly \>liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. |
| Pharmacokinetics (PK) Results for Blinatumomab: Steady-State Concentrations at Week 1, Week 2 and Week 3 for Cycle 1 | Day 2 at least 24 hours after blinatumomab was started and on Day 9 and Day 16 at least 24 hours after blinatumomab dose was increased in the cycle | The steady-state serum concentration (Css), summarized as the observed concentrations collected after at least 10 hours after the start of continuous IV infusion. PK blood samples were analyzed in a central lab. |
| Pharmacokinetics (PK) Results for Blinatumomab: Clearance for Cycle 1 | Day 2 at least 24 hours after blinatumomab was started and on Day 9 and Day 16 at least 24 hours after blinatumomab dose was increased in the cycle | PK blood samples were analyzed in a central lab. |
| Percentage of Participants Who Had Hematopoietic Stem Cell Transplantation (HSCT) | Day 1 up to 14.5 months | Percentage of participants who had HSCT during the Long Term Follow-Up Period. |
| Kaplan-Meier Estimates for Duration of Response | The median (range) follow-up time was 11.5 (8.2, 14.5) months | Duration of response was calculated only for responders during cycle 1. For participants who had CR or PR on the PET/CT scan at the end of the run-in period, response was measured from the start of blinatumomab treatment. For participants who had stable disease at the end of the run-in period, duration was calculated from documentation of the first assessment of either PR or CR on blinatumomab. Progression was defined as the first diagnosis of progressive metabolic response/progressive disease based on PET/CT scan per central or investigator review during the treatment period or relapse based on clinical tumor assessment during the long-term follow up period. Response duration was calculated until the start of new anti-tumor treatment (excluding any stem cell transplantation), PD, or death, whichever was the earliest event. Participants who did not have new anti-tumor treatment (excluding stem cell transplantation), PD, or death were censored at the last tumor assessment date. |
Countries
Canada, France, Germany, Spain, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 12 centers in the European Union (France, Germany, Spain, and the United Kingdom), the United States, and Canada. Of the 54 subjects screened, 47 subjects were enrolled.
Pre-assignment details
The study consisted of a standard of care rituximab-chemotherapy Run-in Period of approximately 21 weeks, a 12- to 16-week blinatumomab Treatment Period, a 30-day safety follow-up, and a Long-term Follow-up Period up to 1 year from the first dose of blinatumomab, or until participant death, whichever occurred first.
Participants by arm
| Arm | Count |
|---|---|
| Blinatumomab Blinatumomab was administered as a continuous intravenous (IV) infusion. Cycle 1 was 12 weeks (84 days) in duration with step dosing of 9 µg/day for 7 days, 28 µg/day for 7 days, 112 µg/day for 6 weeks, followed by a 4-week treatment free time.
An optional 4-week Cycle 2 of blinatumomab was available for participants whose disease did not progress, with step dosing of 9 µg/day for 7 days, 28 µg/day for 7 days, and 112 µg/day for 14 days.
There was a safety follow-up for 30 days. And a long-term follow-up of up to 8 months for a maximum of 1 year from first dose of blinatumomab or until participant death. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Between Run-In and Treatment Periods | Protocol-specified criteria | 2 |
| Long Term Follow-Up Period | Death | 2 |
| Pre-Study Run-In Period | Death | 1 |
| Pre-Study Run-In Period | Protocol-specified criteria | 11 |
| Pre-Study Run-In Period | Withdrawal by Subject | 5 |
| Treatment Period | Adverse Event | 1 |
| Treatment Period | Disease Progression | 1 |
| Treatment Period | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Blinatumomab |
|---|---|
| Age, Continuous | 60.2 years STANDARD_DEVIATION 11.1 |
| Age, Customized < 65 years | 18 Participants |
| Age, Customized >=65 years | 10 Participants |
| Age, Customized <75 years | 25 Participants |
| Age, Customized >=75 years | 3 Participants |
| Disease Stage at Time of Diagnosis Stage I | 0 Participants |
| Disease Stage at Time of Diagnosis Stage IE | 1 Participants |
| Disease Stage at Time of Diagnosis Stage II | 0 Participants |
| Disease Stage at Time of Diagnosis Stage III | 5 Participants |
| Disease Stage at Time of Diagnosis Stage IV | 22 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| International Prognostic Index Score at Diagnosis Score 2 | 2 Participants |
| International Prognostic Index Score at Diagnosis Score 3 | 17 Participants |
| International Prognostic Index Score at Diagnosis Score 4 | 7 Participants |
| International Prognostic Index Score at Diagnosis Score 5 | 2 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black and African American | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 4 Participants |
| Race/Ethnicity, Customized White | 21 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 47 |
| other Total, other adverse events | 26 / 28 |
| serious Total, serious adverse events | 7 / 28 |
Outcome results
Primary
Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment
Overall incidence and severity of treatment-emergent adverse events deemed by investigators to be related to blinatumomab treatment. Severity was graded by investigators according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and based on the scale: Grade 1 = Mild - transient or mild discomfort; Grade 2 = Moderate - mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required; Grade 3 = Severe - marked limitation in activity, assistance usually required; medical intervention required, hospitalization is possible; Grade 4 = Life threatening - extreme limitation in activity, assistance required; medical intervention, hospitalization or hospice care probable; Grade 5 = death.
Time frame: From the start of first infusion of IP to 30 days after the end of last infusion of IP; median (min, max) treatment duration was 56 (16, 84) days
Population: Full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Blinatumomab | Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment | Treatment-related TEAE | 23 Participants |
| Blinatumomab | Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment | Related TEAE severity grade >=3 | 9 Participants |
| Blinatumomab | Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment | Related TEAE severity grade >=4 | 3 Participants |
| Blinatumomab | Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment | Related Serious TEAE | 5 Participants |
| Blinatumomab | Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment | Related TEAE leading to interruption of IP | 3 Participants |
| Blinatumomab | Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment | Related Serious TEAE leading to interruption of IP | 2 Participants |
| Blinatumomab | Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment | Related TEAE leading to discontinuation of IP | 2 Participants |
| Blinatumomab | Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment | Related Serious TEAE leading to discon of IP | 1 Participants |
| Blinatumomab | Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment | Related and Fatal TEAEs | 0 Participants |
Primary
Participants With Treatment-Emergent (Blinatumomab) Adverse Events
Overall incidence and severity of treatment-emergent adverse events occurring during the blinatumomab investigative product (IP) treatment period graded by investigators according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and based on the scale: Grade 1 = Mild - transient or mild discomfort; Grade 2 = Moderate - mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required; Grade 3 = Severe - marked limitation in activity, assistance usually required; medical intervention required, hospitalization is possible; Grade 4 = Life threatening - extreme limitation in activity, assistance required; medical intervention, hospitalization or hospice care probable; Grade 5 = death.
Time frame: From the start of first infusion of IP to 30 days after the end of last infusion of IP; median (min, max) treatment duration was 56 (16, 84) days
Population: Full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Blinatumomab | Participants With Treatment-Emergent (Blinatumomab) Adverse Events | Serious TEAE | 7 Participants |
| Blinatumomab | Participants With Treatment-Emergent (Blinatumomab) Adverse Events | TEAE | 28 Participants |
| Blinatumomab | Participants With Treatment-Emergent (Blinatumomab) Adverse Events | TEAE severity grade >=3 | 11 Participants |
| Blinatumomab | Participants With Treatment-Emergent (Blinatumomab) Adverse Events | TEAE severity grade >=4 | 5 Participants |
| Blinatumomab | Participants With Treatment-Emergent (Blinatumomab) Adverse Events | TEAE leading to interruption of IP | 3 Participants |
| Blinatumomab | Participants With Treatment-Emergent (Blinatumomab) Adverse Events | Serious TEAE leading to interruption of IP | 2 Participants |
| Blinatumomab | Participants With Treatment-Emergent (Blinatumomab) Adverse Events | TEAE leading to discontinuation of IP | 2 Participants |
| Blinatumomab | Participants With Treatment-Emergent (Blinatumomab) Adverse Events | Serious TEAE leading to discontinuation of IP | 1 Participants |
| Blinatumomab | Participants With Treatment-Emergent (Blinatumomab) Adverse Events | Fatal TEAEs | 0 Participants |
Secondary
Complete Response Rate Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period
Tumor response assessment was performed by a central reader according to modified Lugano classification using PET/CT scan. CMR: a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with/without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology.
Time frame: Cycle 1: Day 78 (3 weeks following end of Cycle 1 IP treatment) Treatment Period: Either the Cycle 1 timeframe or approximately Day 128 (3 weeks after Cycle 2 ended) for participants who completed Cycle 2
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Blinatumomab | Complete Response Rate Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period | Cycle 1 | 85.7 percentage of participants |
| Blinatumomab | Complete Response Rate Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period | Entire Treatment Period | 89.3 percentage of participants |
Secondary
Kaplan-Meier Estimates for Duration of Response
Duration of response was calculated only for responders during cycle 1. For participants who had CR or PR on the PET/CT scan at the end of the run-in period, response was measured from the start of blinatumomab treatment. For participants who had stable disease at the end of the run-in period, duration was calculated from documentation of the first assessment of either PR or CR on blinatumomab. Progression was defined as the first diagnosis of progressive metabolic response/progressive disease based on PET/CT scan per central or investigator review during the treatment period or relapse based on clinical tumor assessment during the long-term follow up period. Response duration was calculated until the start of new anti-tumor treatment (excluding any stem cell transplantation), PD, or death, whichever was the earliest event. Participants who did not have new anti-tumor treatment (excluding stem cell transplantation), PD, or death were censored at the last tumor assessment date.
Time frame: The median (range) follow-up time was 11.5 (8.2, 14.5) months
Population: Responder Analysis Set includes all participants in the FAS that achieve objective response (CR or PR as per the Lugano classification) on the PET/CT scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Blinatumomab | Kaplan-Meier Estimates for Duration of Response | NA months |
Secondary
Kaplan-Meier Estimates for Overall Survival (OS) From First Dose of Blinatumomab
OS was calculated as the time from the date of first IP infusion until death due to any cause. Participants who are alive at the date that triggers the analysis were censored at the date last known to be alive. Months were calculated as days from the first dose date of blinatumomab to death/censor date, divided by 30.5.
Time frame: The median (range) follow-up time was 12.0 (10.7, 14.5) months.
Population: Full analysis set (FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Blinatumomab | Kaplan-Meier Estimates for Overall Survival (OS) From First Dose of Blinatumomab | NA months |
Secondary
Kaplan-Meier Estimates for Progression Free Survival (PFS) From First Dose of Blinatumomab
PFS was calculated as the time from the date of first IP infusion until the date of diagnosis of progression of DLBCL or the date of death, whichever was the earliest. The diagnosis of progression of DLBCL was defined as the first diagnosis of progressive metabolic response/progressive disease based on PET/CT scan per central or investigator review during the treatment period or relapse based on clinical tumor assessment during the long-term follow up period. Participants who were alive and did not have progression were censored at the last evaluable non-missing tumor assessment date prior to the analysis trigger date.
Time frame: The median (range) follow-up time was 12.0 (8.2, 14.5)
Population: Full analysis set (FAS)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Blinatumomab | Kaplan-Meier Estimates for Progression Free Survival (PFS) From First Dose of Blinatumomab | NA months |
Secondary
Overall Objective Response Rate (ORR) Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) and Partial Metabolic Response (PMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period
Tumor response assessment was performed by a central reader according to modified Lugano classification using PET/CT scan. Overall objective response rate (ORR) is the percentage of participants with a best overall response of complete metabolic response (CMR) or partial metabolic response (PMR). CMR: a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with/without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PMR: a score 4 (uptake moderately greater than \[\>\] liver) or 5 (uptake markedly \>liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline.
Time frame: Cycle 1: Day 78 (3 weeks following end of Cycle 1 IP treatment) Treatment Period: Either the Cycle 1 timeframe or approximately Day 128 (3 weeks after Cycle 2 ended) for participants who completed Cycle 2
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Blinatumomab | Overall Objective Response Rate (ORR) Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) and Partial Metabolic Response (PMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period | Cycle 1 | 89.3 percentage of participants |
| Blinatumomab | Overall Objective Response Rate (ORR) Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) and Partial Metabolic Response (PMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period | Entire Treatment Period | 92.9 percentage of participants |
Secondary
Percentage of Participants Who Had Hematopoietic Stem Cell Transplantation (HSCT)
Percentage of participants who had HSCT during the Long Term Follow-Up Period.
Time frame: Day 1 up to 14.5 months
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Blinatumomab | Percentage of Participants Who Had Hematopoietic Stem Cell Transplantation (HSCT) | 3.6 percentage of participants |
Secondary
Pharmacokinetics (PK) Results for Blinatumomab: Clearance for Cycle 1
PK blood samples were analyzed in a central lab.
Time frame: Day 2 at least 24 hours after blinatumomab was started and on Day 9 and Day 16 at least 24 hours after blinatumomab dose was increased in the cycle
Population: Pharmacokinetic Analysis Set: participants who received any infusion of blinatumomab and had at least one PK sample collected
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Blinatumomab | Pharmacokinetics (PK) Results for Blinatumomab: Clearance for Cycle 1 | 1.61 L/Hour | Standard Deviation 0.496 |
Secondary
Pharmacokinetics (PK) Results for Blinatumomab: Steady-State Concentrations at Week 1, Week 2 and Week 3 for Cycle 1
The steady-state serum concentration (Css), summarized as the observed concentrations collected after at least 10 hours after the start of continuous IV infusion. PK blood samples were analyzed in a central lab.
Time frame: Day 2 at least 24 hours after blinatumomab was started and on Day 9 and Day 16 at least 24 hours after blinatumomab dose was increased in the cycle
Population: Pharmacokinetic Analysis Set: participants who received any infusion of blinatumomab and had at least one PK sample collected
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Blinatumomab | Pharmacokinetics (PK) Results for Blinatumomab: Steady-State Concentrations at Week 1, Week 2 and Week 3 for Cycle 1 | Cycle 1 Week 1: 9 mcg/day | 288 pg/mL | Standard Deviation 289 |
| Blinatumomab | Pharmacokinetics (PK) Results for Blinatumomab: Steady-State Concentrations at Week 1, Week 2 and Week 3 for Cycle 1 | Cycle 1 Week 2: 28 mcg/day | 795 pg/mL | Standard Deviation 280 |
| Blinatumomab | Pharmacokinetics (PK) Results for Blinatumomab: Steady-State Concentrations at Week 1, Week 2 and Week 3 for Cycle 1 | Cycle 1 Week 3: 112 mcg/day | 3160 pg/mL | Standard Deviation 782 |