Back to resultsA Phase 2, Multicenter, Randomized, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Primary Purpose
Diffuse Large B-Cell Lymphoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MEDI-551 2 mg/kg
Rituximab
ICE
DHAP
Autologous Stem Cell Transplant (ASCT)
MEDI-551 4 mg/kg
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma focused on measuring Lymphoma, Non-Hodgkin's Lymphoma, Diffuse Large B-Cell Lymphoma, DLBCL, B-Cell Malignancy, anti-CD19, monoclonal antibody, second line, ASCT, Refractory
Eligibility Criteria
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
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
Rituximab+ ICE/DHAP
MEDI-551 2 mg/kg + ICE/DHAP
MEDI-551 4 mg/kg + ICE/DHAP
Arm Description
Participants will receive Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and will 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) will be 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.
Participants will receive MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and will be 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) will be 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.
Participants will receive MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and will be 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) will be 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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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).
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 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 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).
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).
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.
Acceptable Dose of MEDI-551
Acceptable dose for MEDI-551 was evaluated based on the benefit-risk analysis.
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).
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).
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.
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.
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.
Mean Serum Concentration of MEDI-551
The mean serum concentration of MEDI-551 were observed.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01453205
Brief Title
A Phase 2, Multicenter, Randomized, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Official Title
A Phase 2 Randomized Open-label Study of MEDI-551 in Adults With Relapsed or Refractory DLBCL
Study Type
Interventional
2. Study Status
Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
February 27, 2012 (Actual)
Primary Completion Date
July 11, 2016 (Actual)
Study Completion Date
July 11, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-Cell Lymphoma
Keywords
Lymphoma, Non-Hodgkin's Lymphoma, Diffuse Large B-Cell Lymphoma, DLBCL, B-Cell Malignancy, anti-CD19, monoclonal antibody, second line, ASCT, Refractory
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
187 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rituximab+ ICE/DHAP
Arm Type
Active Comparator
Arm Description
Participants will receive Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and will 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) will be 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.
Arm Title
MEDI-551 2 mg/kg + ICE/DHAP
Arm Type
Experimental
Arm Description
Participants will receive MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and will be 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) will be 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.
Arm Title
MEDI-551 4 mg/kg + ICE/DHAP
Arm Type
Experimental
Arm Description
Participants will receive MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and will be 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) will be 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.
Intervention Type
Drug
Intervention Name(s)
MEDI-551 2 mg/kg
Other Intervention Name(s)
Inebilizumab
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan; MabThera
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
ICE
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
DHAP
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Autologous Stem Cell Transplant (ASCT)
Intervention Description
Subjects who achieve CR or PR will undergo stem cell harvest and autologous stem cell transplantation (ASCT) following standard institutional protocols.
Intervention Type
Drug
Intervention Name(s)
MEDI-551 4 mg/kg
Other Intervention Name(s)
Inebilizumab
Intervention Description
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).
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
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)
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
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)
Title
Event-Free Survival (EFS)
Description
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)
Title
Overall Survival (OS)
Description
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)
Title
Time to Progression (TTP)
Description
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)
Title
Time to Response (TTR)
Description
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)
Title
Duration of Response (DR)
Description
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)
Title
Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR)
Description
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)
Title
Acceptable Dose of MEDI-551
Description
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)
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description
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)
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Description
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)
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Description
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)
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Description
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)
Title
Number of Participants Who Developed Detectable MEDI-551 Anti-drug Antibodies (ADA)
Description
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)
Title
Mean Serum Concentration of MEDI-551
Description
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
Title
Half-life (T1/2) of MEDI-551
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MedImmune LLC
Organizational Affiliation
MedImmune LLC
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35061
Country
United States
Facility Name
Research Site
City
Burbank
State/Province
California
ZIP/Postal Code
91501
Country
United States
Facility Name
Research Site
City
Palm Springs
State/Province
California
ZIP/Postal Code
92262
Country
United States
Facility Name
Research Site
City
Sylmar
State/Province
California
ZIP/Postal Code
91342
Country
United States
Facility Name
Research Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Research Site
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Research Site
City
Hazard
State/Province
Kentucky
ZIP/Postal Code
41701
Country
United States
Facility Name
Research Site
City
Lafayette
State/Province
Louisiana
ZIP/Postal Code
70503
Country
United States
Facility Name
Research Site
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Facility Name
Research Site
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Research Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Research Site
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Research Site
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
66160
Country
United States
Facility Name
Research Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Research Site
City
Bronx
State/Province
New York
ZIP/Postal Code
10466
Country
United States
Facility Name
Research Site
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58102
Country
United States
Facility Name
Research Site
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45403
Country
United States
Facility Name
Research Site
City
Newark
State/Province
Ohio
ZIP/Postal Code
43055
Country
United States
Facility Name
Research Site
City
Sylvania
State/Province
Ohio
ZIP/Postal Code
43560
Country
United States
Facility Name
Research Site
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Research Site
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Research Site
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37909
Country
United States
Facility Name
Research Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79410
Country
United States
Facility Name
Research Site
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26505
Country
United States
Facility Name
Research Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53266
Country
United States
Facility Name
Research Site
City
St. John
State/Province
New Brunswick
ZIP/Postal Code
E2E5A2
Country
Canada
Facility Name
Research Site
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 1V7
Country
Canada
Facility Name
Research Site
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2H1
Country
Canada
Facility Name
Research Site
City
Brno
ZIP/Postal Code
12808
Country
Czechia
Facility Name
Research Site
City
Praha 2
ZIP/Postal Code
12808
Country
Czechia
Facility Name
Research Site
City
Praha
ZIP/Postal Code
12808
Country
Czechia
Facility Name
Research Site
City
Bordeaux
ZIP/Postal Code
33300
Country
France
Facility Name
Research Site
City
Le Mans
ZIP/Postal Code
72000
Country
France
Facility Name
Research Site
City
Libourne Cedex
ZIP/Postal Code
33205
Country
France
Facility Name
Research Site
City
Marseille
ZIP/Postal Code
13005
Country
France
Facility Name
Research Site
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
Research Site
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Research Site
City
Rouen
ZIP/Postal Code
76100
Country
France
Facility Name
Research Site
City
Tours
ZIP/Postal Code
37100
Country
France
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
10967
Country
Germany
Facility Name
Research Site
City
Frankfurt
ZIP/Postal Code
65929
Country
Germany
Facility Name
Research Site
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Research Site
City
Muenchen
ZIP/Postal Code
80804
Country
Germany
Facility Name
Research Site
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Research Site
City
Wuerzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Research Site
City
Budapest
ZIP/Postal Code
01083
Country
Hungary
Facility Name
Research Site
City
Debrecen
ZIP/Postal Code
04032
Country
Hungary
Facility Name
Research Site
City
Gyor
ZIP/Postal Code
09200
Country
Hungary
Facility Name
Research Site
City
Kaposvar
ZIP/Postal Code
07400
Country
Hungary
Facility Name
Research Site
City
Ashkelon
ZIP/Postal Code
78278
Country
Israel
Facility Name
Research Site
City
Haifa
ZIP/Postal Code
31999
Country
Israel
Facility Name
Research Site
City
Jerusalem
Country
Israel
Facility Name
Research Site
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Research Site
City
Gdynia
ZIP/Postal Code
81-519
Country
Poland
Facility Name
Research Site
City
Lublin
ZIP/Postal Code
20081
Country
Poland
Facility Name
Research Site
City
Nizhny Novgorod
ZIP/Postal Code
603126
Country
Russian Federation
Facility Name
Research Site
City
Saint Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Facility Name
Research Site
City
St. Petersburg
ZIP/Postal Code
191024
Country
Russian Federation
Facility Name
Research Site
City
St. Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Research Site
City
Cadiz
ZIP/Postal Code
11009
Country
Spain
Facility Name
Research Site
City
Girona
ZIP/Postal Code
17007
Country
Spain
Facility Name
Research Site
City
L'Hospitalet de Llobregat
ZIP/Postal Code
08907
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28025
Country
Spain
Facility Name
Research Site
City
Majadahonda
ZIP/Postal Code
28222
Country
Spain
Facility Name
Research Site
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Research Site
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Research Site
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Research Site
City
San Sebastian de los Reyes
ZIP/Postal Code
28702
Country
Spain
Facility Name
Research Site
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Research Site
City
Sevilla
ZIP/Postal Code
41014
Country
Spain
Facility Name
Research Site
City
Valencia
ZIP/Postal Code
46015
Country
Spain
Facility Name
Research Site
City
Valencia
ZIP/Postal Code
46017
Country
Spain
Facility Name
Research Site
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Research Site
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Research Site
City
Izmir
ZIP/Postal Code
35340
Country
Turkey
Facility Name
Research Site
City
Kurupelit
ZIP/Postal Code
55139
Country
Turkey
Facility Name
Research Site
City
Malatya
ZIP/Postal Code
44100
Country
Turkey
Facility Name
Research Site
City
Talas
ZIP/Postal Code
38280
Country
Turkey
12. IPD Sharing Statement
Learn more about this trial
A Phase 2, Multicenter, Randomized, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
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