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.
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)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Diffuse Large B-Cell Lymphoma
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
Lymphoma, Non-Hodgkin's Lymphoma, Diffuse Large B-Cell Lymphoma, DLBCL, B-Cell Malignancy, anti-CD19, monoclonal antibody, second line, ASCT, Refractory
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
99 Years
Minimum Age
18 Years
NCT Id
NCT01453205
Org Class
Industry
Org Full Name
MedImmune LLC
Org Study Id
CD-ON-MEDI-551-1088
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2 Randomized Open-label Study of MEDI-551 in Adults With Relapsed or Refractory DLBCL
Primary Outcomes
Outcome 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.
Outcome Measure
Objective Response Rate (ORR)
Outcome 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 Outcomes
Outcome 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).
Outcome 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)
Outcome Measure
Progression-Free Survival (PFS)
Outcome 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).
Outcome 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)
Outcome Measure
Event-Free Survival (EFS)
Outcome 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).
Outcome 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)
Outcome Measure
Overall Survival (OS)
Outcome 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).
Outcome 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)
Outcome Measure
Time to Progression (TTP)
Outcome 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).
Outcome 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)
Outcome Measure
Time to Response (TTR)
Outcome 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).
Outcome 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)
Outcome Measure
Duration of Response (DR)
Outcome 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.
Outcome 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)
Outcome Measure
Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR)
Outcome Description
Acceptable dose for MEDI-551 was evaluated based on the benefit-risk analysis.
Outcome 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)
Outcome Measure
Acceptable Dose of MEDI-551
Outcome 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).
Outcome 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)
Outcome Measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Outcome 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).
Outcome 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)
Outcome Measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Outcome 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.
Outcome 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)
Outcome Measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Outcome 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.
Outcome 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)
Outcome Measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Outcome 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.
Outcome 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)
Outcome Measure
Number of Participants Who Developed Detectable MEDI-551 Anti-drug Antibodies (ADA)
Outcome Description
The mean serum concentration of MEDI-551 were observed.
Outcome 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
Outcome Measure
Mean Serum Concentration of MEDI-551
Outcome Description
Terminal elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the serum.
Outcome 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)
Outcome Measure
Half-life (T1/2) of MEDI-551
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
99
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Noah Kornblum
Investigator Email
nkornblu@montefiore.org
Investigator Phone
718-920-4826
Categories Mesh Debug
Cancer --- NEOPLASMS
Blood & Bone Marrow Cancers --- LYMPHOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- LYMPHATIC DISEASES
Blood & Bone Marrow Cancers --- IMMUNOPROLIFERATIVE DISORDERS
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
MeSH Terms
LYMPHOMA, LARGE B-CELL, DIFFUSE
LYMPHOMA
LYMPHOMA, NON-HODGKIN
LYMPHOMA, B-CELL
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
HEMIC AND LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
IMMUNE SYSTEM DISEASES
INEBILIZUMAB
RITUXIMAB
ICE
ANTIBODIES, MONOCLONAL, MURINE-DERIVED
ANTIBODIES, MONOCLONAL
ANTIBODIES
IMMUNOGLOBULINS
IMMUNOPROTEINS
BLOOD PROTEINS
PROTEINS
AMINO ACIDS, PEPTIDES, AND PROTEINS
SERUM GLOBULINS
GLOBULINS
WATER
HYDROXIDES
ALKALIES
INORGANIC CHEMICALS
ANIONS
IONS
ELECTROLYTES
OXIDES
OXYGEN COMPOUNDS
ENVIRONMENT
ECOLOGICAL AND ENVIRONMENTAL PHENOMENA
BIOLOGICAL PHENOMENA
WEATHER
METEOROLOGICAL CONCEPTS
ENVIRONMENT AND PUBLIC HEALTH