Diffuse Large B-Cell Lymphoma
Conditions
Keywords
Lymphoma, Non-Hodgkin's Lymphoma, Diffuse Large B-Cell Lymphoma, DLBCL, B-Cell Malignancy, anti-CD19, monoclonal antibody, second line, ASCT, Refractory
Brief summary
The overall purpose of the study is to determine if MEDI-551, when used in combination with salvage chemotherapy, Ifosfamide-carboplatin-etoposide (ICE) or Dexamethasone-cytarabine (DHAP) in patients with relapsed or refractory DLBCL who are eligible for Autologous Stem Cell Transplant (ASCT), has superior efficacy compared to rituximab in the same population.
Interventions
DRUGMEDI-551 2 mg/kg
MEDI-551 at the assigned dose will be administered via Intravenous (IV) infusion. Subjects will receive 3 cycles of M-ICE or M-DHAP unless CR is achieved at the end of Cycle 2, disease progression is noted at the end of Cycle 2, or a significant/serious drug related toxicity occurs (as per the opinion of the investigator).
DRUGRituximab
Rituximab at 375 mg/m2 will be administered via IV infusion 2 days before the start of Cycle 1 and on Day 1 of each cycle. The infusion time for rituximab will be 50 400 mg/hr, depending on subject's tolerance. Subjects will receive 3 cycles of Rituximab with Ice (R ICE) or Rituximab with DHAP (R-DHAP) unless CR is achieved at the end of Cycle 2, disease progression is noted at the end of Cycle 2, or a significant/serious drug related toxicity occurs (as per the opinion of the investigator).
DRUGICE
ICE will be administered via IV infusion as follows: ifosfamide 5 g/m2 continuously for 24 hours with mesna on Days 2 and 3; carboplatin AUC=5 mg/mL x min \[800 mg maximum) on Day 2; etoposide 100 mg/m2 on Days 1, 2, and 3) in 21-day cycles.
DRUGDHAP
DHAP will be administered via IV infusion as follows: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m2 continuously for 24 hours on Day 1 of dosing cycle; cytarabine 2 g/m2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
Subjects who achieve CR or PR will undergo stem cell harvest and autologous stem cell transplantation (ASCT) following standard institutional protocols.
DRUGMEDI-551 4 mg/kg
MEDI-551 at the assigned dose will be administered via Intravenous (IV) infusion. Subjects will receive 3 cycles of M-ICE or M-DHAP unless CR is achieved at the end of Cycle 2, disease progression is noted at the end of Cycle 2, or a significant/serious drug related toxicity occurs (as per the opinion of the investigator).
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed aggressive B-cell DLBCL, including FL transforming to DLBCL & Grade III FL * Relapsed from or refractory to at least one treatment containing rituximab or another anti-CD20 based immunotherapy combined with anthracycline- or anthracenedione-based chemotherapy * Eligible for ASCT * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Life expectancy of ≥ 12 weeks * Adequate hematological function
Exclusion criteria
* Any chemotherapy, radiotherapy, immunotherapy, biologic, investigational or hormonal therapy for treatment of lymphoma within 28 days prior to treatment * Previous cancer therapy for DLBCL other than anthracycline- or anthracenedione based chemoimmunotherapy, monotherapy rituximab prior to first line therapy and/or as a maintenance therapy, or limited field radiotherapy * Prior autologous or allogeneic SCT * New York Heart Association ≥ Class II congestive heart failure; Clinically significant abnormality on ECG * History of other invasive malignancy within 5 years except for localized/in situ, carcinomas such as cervical carcinoma in situ. * Evidence of active infection * Documented current central nervous system involvement by leukemia or lymphoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant) | Objective Response Rate is defined as the proportion of participants with a best response of complete response (CR) or partial response (PR) according to the International Working Group criteria. CR is defined as disappearance of all evidence of disease. PR is defined as 50 percent (%) decrease in the sum of the product of the perpendicular diameters (SPD) of up to 6 largest dominant nodal masses and greater than or equal to (\>=) 50% decrease in SPD of spleen/liver nodules. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival (EFS) | From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant) | Event-Free Survival (EFS) is defined as the time from randomization until the first documentation of EFS events which include PD, initiation of alternative antitumor treatment or death due to any cause, whichever occurs first according to the International Working Group criteria. PD is defined as appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \>50% increase from nadir in the SPD of any previous lesions. EFS (months) = (Date of EFS or censoring - Date of randomization + 1) / (365.25/12). |
| Overall Survival (OS) | From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant) | Overall survival is defined as the time from randomization until death due to any cause according to the International Working Group criteria. OS (months) = (Date of death or censoring - Date of randomization + 1) / (365.25/12). |
| Time to Progression (TTP) | From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant) | Time to Progression (TTP) is defined as the time from randomization until the first documentation of PD according to the International Working Group criteria. PD is defined as appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \>50% increase from nadir in the SPD of any previous lesions. TTP (months) = (Date of PD or censoring - Date of randomization + 1) / (365.25/12). |
| Time to Response (TTR) | From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant) | Time to response (TTR) is defined as the time from randomization until the first documentation of disease response according to the International Working Group criteria. Only participants who have achieved objective response (confirmed CR or confirmed PR) assessed by investigator were evaluated for TTR. CR is defined as disappearance of all evidence of disease. PR is defined as 50% decrease in the SPD of up to 6 largest dominant nodal masses and \>= 50% decrease in SPD of spleen/liver nodules. TTR (months) = (Date of first disease response - Date of randomization + 1) / (365.25/12). |
| Duration of Response (DR) | From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant) | Duration of Response (DR) is defined as time from start of first documented objective response (confirmed CR or confirmed PR) to first documented PD according to the International Working Group criteria. CR is defined as disappearance of all evidence of disease. PR is defined as 50% decrease in the SPD of up to 6 largest dominant nodal masses and \>= 50% decrease in SPD of spleen/liver nodules. PD: appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \> 50% increase from nadir in the SPD of any previous lesions. Only participants who have achieved objective response assessed by investigator were evaluated. DR calculated as (months) = (Date of PD or censoring - Date of first disease response + 1)/ (365.25/12). |
| Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant) | The best overall response was calculated, based upon the disease assessments recorded during the study visits, and summarized with the number of participants for the following categories: CR, PR, stable disease (SD), PD, and unknown. Responses were assessed according to the International Working Group criteria. CR: disappearance of all evidence of disease; PR: 50% decrease in the SPD of up to 6 largest dominant nodal masses and \>= 50% decrease in SPD of spleen/liver nodules; PD: appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \>50% increase from nadir in the SPD of any previous lesions; SD: failure to attain CR/PR or PD. |
| Acceptable Dose of MEDI-551 | After the administration of the first dose of MEDI-551 (7 days before the Cycle 1) to last dose of MEDI-551 (Cycle 3 Day 1) (each cycle of 21 days) | Acceptable dose for MEDI-551 was evaluated based on the benefit-risk analysis. |
| Progression-Free Survival (PFS) | From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant) | Progression-free survival (PFS) is defined as the time from randomization until the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first according to the International Working Group criteria. PD is defined as appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \>50% increase from nadir in the SPD of any previous lesions. PFS (months) = (Date of PD/death or censoring - Date of randomization + 1) / (365.25/12). |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant) | An abnormal laboratory finding that was judged by the investigator to be clinically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-551, or events absent at baseline that emerged after administration of MEDI-551, for the period extending to 90 days after the end of study treatment (EOT). |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant) | An abnormal laboratory findings that was judged by the investigator to be clinically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-551, or events absent at baseline that emerged after administration of MEDI-551, for the period extending to 90 days after the end of study treatment. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant) | Vital signs included parameters such as heart rate, blood pressure, temperature, and respiratory rate. An abnormal vital signs and ECG findings that was judged by the investigator to be clinically significant was reported an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-551, or events absent at baseline that emerged after administration of MEDI-551, for the period extending to 90 days after the end of study treatment. |
| Number of Participants Who Developed Detectable MEDI-551 Anti-drug Antibodies (ADA) | 7 days before the start of Cycle 1, Day 1 of each subsequent Cycle, EOT, and post EOT on Days 30, 60, 90 and 270 (up to 36 months from the randomization of last participant) | A participant was considered ADA-positive across the study if they had a positive reading (titer of 50 or higher) at any time point during the study. |
| Mean Serum Concentration of MEDI-551 | Cycle 1 Day -7 Post dose, pre-dose and postdose on Day 1, post-dose on Days 4, 8, 15 of Cycle 1, pre-dose and postdose on Day 1 of Cycle 2 and Cycle 3 | The mean serum concentration of MEDI-551 were observed. |
| Half-life (T1/2) of MEDI-551 | Cycle 1 and EOT (Day 21 of Cycle 3 [each cycle of 21 days] or earlier cycles if treatment stopped before Cycle 3) | Terminal elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the serum. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant) | An Adverse Event (AE) is any unfavourable and unintended signs, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. Serious adverse event (SAE) is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 90 days after the end of treatment (EOT). |
Countries
Canada, Czechia, France, Germany, Hungary, Israel, Poland, Russia, Spain, Turkey (Türkiye), United States
Participant flow
Recruitment details
The study was conducted from 27Feb2012 to 17Jun2016.
Pre-assignment details
A total of 256 participants were screened, of which 187 participants were randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Rituximab+ ICE/DHAP Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles. | 80 |
| MEDI-551 2 mg/kg + ICE/DHAP Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles. | 52 |
| MEDI-551 4 mg/kg + ICE/DHAP Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles. | 55 |
| TOTAL Total of all reporting groups | 187 |
| Total | 374 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 24 | 22 | 18 |
| Overall Study | Lost to Follow-up | 3 | 0 | 1 |
| Overall Study | Other | 45 | 27 | 35 |
| Overall Study | Withdrawal by Subject | 8 | 3 | 0 |
Baseline characteristics
| Characteristic | Rituximab+ ICE/DHAP | MEDI-551 2 mg/kg + ICE/DHAP | MEDI-551 4 mg/kg + ICE/DHAP | TOTAL |
|---|---|---|---|---|
| Age, Continuous | 56.4 YEARS STANDARD_DEVIATION 12.3 | 56.9 YEARS STANDARD_DEVIATION 11.4 | 55.9 YEARS STANDARD_DEVIATION 11.6 | 56.4 YEARS STANDARD_DEVIATION 11.8 |
| Age, Customized < 65 YEARS | 60 Participants | 35 Participants | 43 Participants | 138 Participants |
| Age, Customized >= 65 YEARS | 20 Participants | 17 Participants | 12 Participants | 49 Participants |
| Sex: Female, Male Female | 35 Participants | 19 Participants | 24 Participants | 78 Participants |
| Sex: Female, Male Male | 45 Participants | 33 Participants | 31 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 78 / 79 | 49 / 52 | 52 / 54 |
| serious Total, serious adverse events | 33 / 79 | 25 / 52 | 27 / 54 |
Outcome results
Primary
Objective Response Rate (ORR)
Objective Response Rate is defined as the proportion of participants with a best response of complete response (CR) or partial response (PR) according to the International Working Group criteria. CR is defined as disappearance of all evidence of disease. PR is defined as 50 percent (%) decrease in the sum of the product of the perpendicular diameters (SPD) of up to 6 largest dominant nodal masses and greater than or equal to (\>=) 50% decrease in SPD of spleen/liver nodules.
Time frame: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
Population: Intent-To-Treat population included all participants who were randomized into the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+ ICE/DHAP | Objective Response Rate (ORR) | 47.5 Percentage of participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Objective Response Rate (ORR) | 46.2 Percentage of participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Objective Response Rate (ORR) | 43.6 Percentage of participants |
p-value: 0.5543Cochran-Mantel-Haenszel
Secondary
Acceptable Dose of MEDI-551
Acceptable dose for MEDI-551 was evaluated based on the benefit-risk analysis.
Time frame: After the administration of the first dose of MEDI-551 (7 days before the Cycle 1) to last dose of MEDI-551 (Cycle 3 Day 1) (each cycle of 21 days)
Population: All participants who were randomized into the study and received MEDI-551.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab+ ICE/DHAP | Acceptable Dose of MEDI-551 | 4 milligram per kilogram (mg/kg) |
Secondary
Duration of Response (DR)
Duration of Response (DR) is defined as time from start of first documented objective response (confirmed CR or confirmed PR) to first documented PD according to the International Working Group criteria. CR is defined as disappearance of all evidence of disease. PR is defined as 50% decrease in the SPD of up to 6 largest dominant nodal masses and \>= 50% decrease in SPD of spleen/liver nodules. PD: appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \> 50% increase from nadir in the SPD of any previous lesions. Only participants who have achieved objective response assessed by investigator were evaluated. DR calculated as (months) = (Date of PD or censoring - Date of first disease response + 1)/ (365.25/12).
Time frame: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
Population: Intent-To-Treat population included all participants who were randomized into the study. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab+ ICE/DHAP | Duration of Response (DR) | NA months |
| MEDI-551 2 mg/kg + ICE/DHAP | Duration of Response (DR) | 7.1 months |
| MEDI-551 4 mg/kg + ICE/DHAP | Duration of Response (DR) | 7.9 months |
Secondary
Event-Free Survival (EFS)
Event-Free Survival (EFS) is defined as the time from randomization until the first documentation of EFS events which include PD, initiation of alternative antitumor treatment or death due to any cause, whichever occurs first according to the International Working Group criteria. PD is defined as appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \>50% increase from nadir in the SPD of any previous lesions. EFS (months) = (Date of EFS or censoring - Date of randomization + 1) / (365.25/12).
Time frame: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
Population: Intent-To-Treat population included all participants who were randomized into the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab+ ICE/DHAP | Event-Free Survival (EFS) | 4.7 months |
| MEDI-551 2 mg/kg + ICE/DHAP | Event-Free Survival (EFS) | 4.2 months |
| MEDI-551 4 mg/kg + ICE/DHAP | Event-Free Survival (EFS) | 5.9 months |
p-value: 0.7412Log Rank
Secondary
Half-life (T1/2) of MEDI-551
Terminal elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the serum.
Time frame: Cycle 1 and EOT (Day 21 of Cycle 3 [each cycle of 21 days] or earlier cycles if treatment stopped before Cycle 3)
Population: Participants who received MEDI-551 were analyzed for this end point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab+ ICE/DHAP | Half-life (T1/2) of MEDI-551 | Cycle 1 | 14.4 Day | Standard Deviation 5.09 |
| Rituximab+ ICE/DHAP | Half-life (T1/2) of MEDI-551 | End of Treatment | 18.9 Day | Standard Deviation 4.34 |
| MEDI-551 2 mg/kg + ICE/DHAP | Half-life (T1/2) of MEDI-551 | Cycle 1 | 16.5 Day | Standard Deviation 10.5 |
| MEDI-551 2 mg/kg + ICE/DHAP | Half-life (T1/2) of MEDI-551 | End of Treatment | 20.2 Day | Standard Deviation 5.73 |
Secondary
Mean Serum Concentration of MEDI-551
The mean serum concentration of MEDI-551 were observed.
Time frame: Cycle 1 Day -7 Post dose, pre-dose and postdose on Day 1, post-dose on Days 4, 8, 15 of Cycle 1, pre-dose and postdose on Day 1 of Cycle 2 and Cycle 3
Population: Participants who received MEDI-551 were analyzed for this end point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rituximab+ ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 1 Day 4 | 38.8 mcg/mL | Standard Deviation 14.6 |
| Rituximab+ ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 1 Day-7 Post Dose | 47.0 mcg/mL | Standard Deviation 23.7 |
| Rituximab+ ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 1 Day 1 Pre Dose | 16.7 mcg/mL | Standard Deviation 5.81 |
| Rituximab+ ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 1 Day 1 Post Dose | 64.8 mcg/mL | Standard Deviation 26.4 |
| Rituximab+ ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 1 Day 8 | 30.6 mcg/mL | Standard Deviation 9.69 |
| Rituximab+ ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 1 Day 15 | 19.4 mcg/mL | Standard Deviation 6.19 |
| Rituximab+ ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 2 Day 1 Pre Dose | 15.0 mcg/mL | Standard Deviation 5.45 |
| Rituximab+ ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 2 Day 1 Post Dose | 52.3 mcg/mL | Standard Deviation 18.7 |
| Rituximab+ ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 3 Day 1 Pre Dose | 14.0 mcg/mL | Standard Deviation 6.5 |
| Rituximab+ ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 3 Day 1 Post Dose | 52.4 mcg/mL | Standard Deviation 16.9 |
| MEDI-551 2 mg/kg + ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 2 Day 1 Post Dose | 112 mcg/mL | Standard Deviation 32.6 |
| MEDI-551 2 mg/kg + ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 1 Day 4 | 71.9 mcg/mL | Standard Deviation 23 |
| MEDI-551 2 mg/kg + ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 1 Day 15 | 44.7 mcg/mL | Standard Deviation 25 |
| MEDI-551 2 mg/kg + ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 1 Day-7 Post Dose | 83.8 mcg/mL | Standard Deviation 21.9 |
| MEDI-551 2 mg/kg + ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 3 Day 1 Post Dose | 116 mcg/mL | Standard Deviation 30.9 |
| MEDI-551 2 mg/kg + ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 1 Day 1 Pre Dose | 33.1 mcg/mL | Standard Deviation 16.3 |
| MEDI-551 2 mg/kg + ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 2 Day 1 Pre Dose | 30.9 mcg/mL | Standard Deviation 14.3 |
| MEDI-551 2 mg/kg + ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 1 Day 1 Post Dose | 116 mcg/mL | Standard Deviation 41.3 |
| MEDI-551 2 mg/kg + ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 3 Day 1 Pre Dose | 36.4 mcg/mL | Standard Deviation 18.7 |
| MEDI-551 2 mg/kg + ICE/DHAP | Mean Serum Concentration of MEDI-551 | Cycle 1 Day 8 | 69.3 mcg/mL | Standard Deviation 25.1 |
Secondary
Number of Participants Who Developed Detectable MEDI-551 Anti-drug Antibodies (ADA)
A participant was considered ADA-positive across the study if they had a positive reading (titer of 50 or higher) at any time point during the study.
Time frame: 7 days before the start of Cycle 1, Day 1 of each subsequent Cycle, EOT, and post EOT on Days 30, 60, 90 and 270 (up to 36 months from the randomization of last participant)
Population: Safety population included all participants who received any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rituximab+ ICE/DHAP | Number of Participants Who Developed Detectable MEDI-551 Anti-drug Antibodies (ADA) | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants Who Developed Detectable MEDI-551 Anti-drug Antibodies (ADA) | 0 Participants |
Secondary
Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR)
The best overall response was calculated, based upon the disease assessments recorded during the study visits, and summarized with the number of participants for the following categories: CR, PR, stable disease (SD), PD, and unknown. Responses were assessed according to the International Working Group criteria. CR: disappearance of all evidence of disease; PR: 50% decrease in the SPD of up to 6 largest dominant nodal masses and \>= 50% decrease in SPD of spleen/liver nodules; PD: appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \>50% increase from nadir in the SPD of any previous lesions; SD: failure to attain CR/PR or PD.
Time frame: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
Population: ITT population included all participants who were randomized into the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab+ ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | PROGRESSIVE DISEASE (PD) | 5 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | STABLE DISEASE (SD) | 17 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | COMPLETE RESPONSE (CR) | 20 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | PARTIAL RESPONSE (PR) | 18 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | UNKNOWN | 20 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | STABLE DISEASE (SD) | 12 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | COMPLETE RESPONSE (CR) | 6 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | PARTIAL RESPONSE (PR) | 18 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | PROGRESSIVE DISEASE (PD) | 5 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | UNKNOWN | 11 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | UNKNOWN | 12 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | PROGRESSIVE DISEASE (PD) | 5 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | COMPLETE RESPONSE (CR) | 12 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | STABLE DISEASE (SD) | 14 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR) | PARTIAL RESPONSE (PR) | 12 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An Adverse Event (AE) is any unfavourable and unintended signs, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. Serious adverse event (SAE) is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 90 days after the end of treatment (EOT).
Time frame: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
Population: Safety population included all participants who received any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 33 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 78 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 51 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 25 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 52 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 27 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
An abnormal laboratory findings that was judged by the investigator to be clinically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-551, or events absent at baseline that emerged after administration of MEDI-551, for the period extending to 90 days after the end of study treatment.
Time frame: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
Population: Safety population included all participants who received any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hepatic enzyme increased | 1 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Alanine aminotransferase increased | 7 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperuricaemia | 5 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Gamma-glutamyltransferase increased | 9 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Aspartate aminotransferase increased | 5 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypernatraemia | 3 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood uric acid increased | 1 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood alkaline phosphatase increased | 2 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Calcium deficiency | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood uric acid decreased | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood bicarbonate decreased | 1 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypoalbuminaemia | 3 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood potassium decreased | 2 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood bilirubin increased | 1 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperbilirubinaemia | 1 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood magnesium decreased | 2 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood chloride increased | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood lactate dehydrogenase increased | 2 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood creatinine increased | 10 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Urine sodium increased | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypocalcaemia | 11 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperglycaemia | 12 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Proteinuria | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypoglycaemia | 1 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperphosphataemia | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Glucose urine present | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypokalaemia | 24 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypermagnesaemia | 3 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hematuria | 2 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypomagnesaemia | 17 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypercalcaemia | 2 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Dysuria | 2 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyponatraemia | 8 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypertriglyerideaemia | 1 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Transaminases increased | 1 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypophosphataemia | 4 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperkalaemia | 2 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Protein total decreased | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypoproteinaemia | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Electrolyte imbalance | 2 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypomagnesaemia | 6 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperbilirubinaemia | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypernatraemia | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperphosphataemia | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypertriglyerideaemia | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperuricaemia | 4 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypoalbuminaemia | 4 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypocalcaemia | 6 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypoglycaemia | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypokalaemia | 13 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood chloride increased | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyponatraemia | 2 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypophosphataemia | 3 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypoproteinaemia | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Alanine aminotransferase increased | 2 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Aspartate aminotransferase increased | 2 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood alkaline phosphatase increased | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood bicarbonate decreased | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood bilirubin increased | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood creatinine increased | 5 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood lactate dehydrogenase increased | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood magnesium decreased | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood potassium decreased | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood uric acid decreased | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood uric acid increased | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Gamma-glutamyltransferase increased | 3 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hepatic enzyme increased | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Protein total decreased | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Transaminases increased | 2 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Dysuria | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hematuria | 3 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Glucose urine present | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Proteinuria | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Urine sodium increased | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Calcium deficiency | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Electrolyte imbalance | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypercalcaemia | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperglycaemia | 9 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperkalaemia | 2 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypermagnesaemia | 2 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypertriglyerideaemia | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hepatic enzyme increased | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypophosphataemia | 3 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperbilirubinaemia | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Protein total decreased | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyponatraemia | 2 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Electrolyte imbalance | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Transaminases increased | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypomagnesaemia | 11 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperphosphataemia | 2 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Dysuria | 3 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypokalaemia | 14 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypermagnesaemia | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hematuria | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypoglycaemia | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypercalcaemia | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Glucose urine present | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypocalcaemia | 7 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypernatraemia | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Proteinuria | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood creatinine increased | 7 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood chloride increased | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypoalbuminaemia | 3 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood lactate dehydrogenase increased | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood bilirubin increased | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperkalaemia | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood magnesium decreased | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood bicarbonate decreased | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Urine sodium increased | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood potassium decreased | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood alkaline phosphatase increased | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperuricaemia | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood uric acid decreased | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Aspartate aminotransferase increased | 6 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hyperglycaemia | 2 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Blood uric acid increased | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Alanine aminotransferase increased | 4 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Calcium deficiency | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Gamma-glutamyltransferase increased | 3 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis) | Hypoproteinaemia | 1 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
An abnormal laboratory finding that was judged by the investigator to be clinically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-551, or events absent at baseline that emerged after administration of MEDI-551, for the period extending to 90 days after the end of study treatment (EOT).
Time frame: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
Population: Safety population included all participants who received any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Lymphopenia | 4 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Febrile neutropenia | 16 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Granulocytopenia | 3 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Leukopenia | 9 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Anaemia | 47 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Neutropenia | 30 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Pancytopenia | 2 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Thromobocytopenia | 49 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Activated partial thromboplastin time prolonged | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Blood immunoglobulin g decreased | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Blood immunoglobulin m decreased | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Haemoglobin decreased | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Immunoglobulins decreased | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Lymphocyte count decreased | 9 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Neutrophil count decreased | 7 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Platelet count decreased | 12 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Platelet count increased | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | White blood cell count decreased | 6 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | White blood cell count decreased | 5 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Anaemia | 32 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Blood immunoglobulin g decreased | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Immunoglobulins decreased | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Febrile neutropenia | 9 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Neutrophil count decreased | 6 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Platelet count decreased | 8 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Granulocytopenia | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Blood immunoglobulin m decreased | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Platelet count increased | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Leukopenia | 6 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Activated partial thromboplastin time prolonged | 2 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Lymphocyte count decreased | 4 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Lymphopenia | 2 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Thromobocytopenia | 24 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Haemoglobin decreased | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Neutropenia | 15 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Pancytopenia | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Neutropenia | 20 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Pancytopenia | 3 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Thromobocytopenia | 29 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Neutrophil count decreased | 8 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Activated partial thromboplastin time prolonged | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | White blood cell count decreased | 6 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Blood immunoglobulin g decreased | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Blood immunoglobulin m decreased | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Platelet count decreased | 10 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Haemoglobin decreased | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Anaemia | 33 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Febrile neutropenia | 12 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Immunoglobulins decreased | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Granulocytopenia | 2 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Leukopenia | 10 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Lymphopenia | 3 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Lymphocyte count decreased | 3 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results | Platelet count increased | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Vital signs included parameters such as heart rate, blood pressure, temperature, and respiratory rate. An abnormal vital signs and ECG findings that was judged by the investigator to be clinically significant was reported an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-551, or events absent at baseline that emerged after administration of MEDI-551, for the period extending to 90 days after the end of study treatment.
Time frame: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
Population: Safety population included all participants who received any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Systolic dysfunction | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Arrhythmia | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Heart rate irregular | 1 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Tachycardia | 3 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Extrasystoles | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Electrocardiogram QT prolonged | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Pyrexia | 17 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Hypotension | 10 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Electrocardiogram abnormal | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Blood pressure increased | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Dyspnoea exertional | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Carbon dioxide decreased | 1 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Palpitations | 2 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Hypertension | 5 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Dyspnoea | 11 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Sinus arrhythmia | 0 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Bradycardia | 3 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Weight increased | 1 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Sinus bradycardia | 1 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Atrial fibrillation | 1 Participants |
| Rituximab+ ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Weight decreased | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Dyspnoea exertional | 3 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Arrhythmia | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Atrial fibrillation | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Bradycardia | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Extrasystoles | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Palpitations | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Sinus arrhythmia | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Sinus bradycardia | 2 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Systolic dysfunction | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Tachycardia | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Pyrexia | 14 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Blood pressure increased | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Carbon dioxide decreased | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Electrocardiogram abnormal | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Electrocardiogram QT prolonged | 2 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Heart rate irregular | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Weight decreased | 1 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Weight increased | 0 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Dyspnoea | 7 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Hypertension | 2 Participants |
| MEDI-551 2 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Hypotension | 4 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Systolic dysfunction | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Atrial fibrillation | 2 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Heart rate irregular | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Sinus bradycardia | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Hypotension | 8 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Weight decreased | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Sinus arrhythmia | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Hypertension | 3 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Weight increased | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Palpitations | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Arrhythmia | 2 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Dyspnoea | 8 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Blood pressure increased | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Extrasystoles | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Carbon dioxide decreased | 0 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Pyrexia | 11 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Bradycardia | 2 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Electrocardiogram abnormal | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Tachycardia | 2 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Dyspnoea exertional | 1 Participants |
| MEDI-551 4 mg/kg + ICE/DHAP | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities | Electrocardiogram QT prolonged | 2 Participants |
Secondary
Overall Survival (OS)
Overall survival is defined as the time from randomization until death due to any cause according to the International Working Group criteria. OS (months) = (Date of death or censoring - Date of randomization + 1) / (365.25/12).
Time frame: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
Population: Intent-To-Treat population included all participants who were randomized into the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab+ ICE/DHAP | Overall Survival (OS) | NA months |
| MEDI-551 2 mg/kg + ICE/DHAP | Overall Survival (OS) | NA months |
| MEDI-551 4 mg/kg + ICE/DHAP | Overall Survival (OS) | 23.0 months |
p-value: 0.9996Log Rank
Secondary
Progression-Free Survival (PFS)
Progression-free survival (PFS) is defined as the time from randomization until the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first according to the International Working Group criteria. PD is defined as appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \>50% increase from nadir in the SPD of any previous lesions. PFS (months) = (Date of PD/death or censoring - Date of randomization + 1) / (365.25/12).
Time frame: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
Population: Intent-To-Treat population included all participants who were randomized into the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab+ ICE/DHAP | Progression-Free Survival (PFS) | 6.1 months |
| MEDI-551 2 mg/kg + ICE/DHAP | Progression-Free Survival (PFS) | 6.6 months |
| MEDI-551 4 mg/kg + ICE/DHAP | Progression-Free Survival (PFS) | 7.7 months |
p-value: 0.8567Log Rank
Secondary
Time to Progression (TTP)
Time to Progression (TTP) is defined as the time from randomization until the first documentation of PD according to the International Working Group criteria. PD is defined as appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \>50% increase from nadir in the SPD of any previous lesions. TTP (months) = (Date of PD or censoring - Date of randomization + 1) / (365.25/12).
Time frame: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
Population: Intent-To-Treat population included all participants who were randomized into the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab+ ICE/DHAP | Time to Progression (TTP) | 4.9 months |
| MEDI-551 2 mg/kg + ICE/DHAP | Time to Progression (TTP) | 4.2 months |
| MEDI-551 4 mg/kg + ICE/DHAP | Time to Progression (TTP) | 5.9 months |
p-value: 0.1686Log Rank
Secondary
Time to Response (TTR)
Time to response (TTR) is defined as the time from randomization until the first documentation of disease response according to the International Working Group criteria. Only participants who have achieved objective response (confirmed CR or confirmed PR) assessed by investigator were evaluated for TTR. CR is defined as disappearance of all evidence of disease. PR is defined as 50% decrease in the SPD of up to 6 largest dominant nodal masses and \>= 50% decrease in SPD of spleen/liver nodules. TTR (months) = (Date of first disease response - Date of randomization + 1) / (365.25/12).
Time frame: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
Population: ITT population included all participants who were randomized into the study. Here, N is number of participants analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab+ ICE/DHAP | Time to Response (TTR) | 1.7 months |
| MEDI-551 2 mg/kg + ICE/DHAP | Time to Response (TTR) | 2.3 months |
| MEDI-551 4 mg/kg + ICE/DHAP | Time to Response (TTR) | 2.3 months |