Safety/Efficacy of MEDI-551 in Combination With Immunomodulating Therapies in Subjects With Aggressive B-cell Lymphomas
- Conditions
- Relapsed/Refractory Aggressive B-cell Lymphomas
- Interventions
- Registration Number
- NCT02271945
- Lead Sponsor
- MedImmune LLC
- Brief Summary
This is a Phase 1b/2 open-label study to evaluate the safety/efficacy of MEDI-551 + MEDI0680 in participants with relapsed or refractory aggressive B-cell lymphomas who have failed 1-2 prior lines of therapy.
- Detailed Description
This is a Phase 1b/2, multicenter, open-label, study of MEDI-551 in combination with immunomodulating therapy evaluating the safety, tolerability, pharmacokinetics, immunogenicity and anti-tumor activity in subjects with relapsed or refractory aggressive B-cell lymphomas
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 10
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MEDI-551 12 mg/kg and MEDI0680 10 mg/kg MEDI0680 10 mg/kg Participants will receive IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13. MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg MEDI0680 2.5 mg/kg Participants will receive intravenous (IV) infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13. MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kg MEDI-551 12 mg/kg Participants will receive intravenous (IV) infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13. MEDI-551 12 mg/kg and MEDI0680 10 mg/kg MEDI-551 12 mg/kg Participants will receive IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) Vital signs included parameters such as blood pressure, temperature, respiratory rate, and pulse oximetry. An abnormal vital signs and physical findings that was judged by the investigator to be medically significant was reported an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, for the period extending to 90 days after the end of study treatment.
Number of Participants With Best Overall Response Day 1 to Day 28 of Cycle 13 (28-day cycle) 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: complete response (disappearance of all evidence of disease), partial response (regression of measurable disease and no new sites), stable disease (SD), progessive disease (PD), and non- evaluable (NE).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Treatment-Emergent Serious Adverse Events (TESAEs) From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) 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. 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 Clinical Laboratory Abnormalities From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) An abnormal laboratory findings that was judged by the investigator to be medically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, for the period extending to 90 days after the end of study drug.
Maximum Tolerated Dose (MTD) of MEDI-551 Day 1 to Day 28 of Cycle 1 (28-day cycle) The Maximum Tolerated Dose, defined as the highest dose where less than or equal to (\<= 1) out of 6 subjects experiences a dose limiting toxicity (DLT) during the DLT evaluation period (Day 1 to Day 28 of Cycle 1) or the highest protocol specified dose not exceeding MTD.
- Secondary Outcome Measures
Name Time Method Mean Peak and Trough Concentrations of MEDI551 End of Infusion (EOI) of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1 The mean peak and Trough concentration of MEDI551 were observed. Peak is the end of infusion measurement and the Trough is the pre-dose measurement.
Mean Peak and Trough Concentrations of MEDI0680 EOI of Cycle 1 Day 2; Pre-dose and EOI of C1D15, C2D1, C3D1 and C4D1 The mean peak and Trough concentration of MEDI0680 were observed. Peak is the end of infusion measurement and the Trough is the pre-dose measurement.
Duration of Complete Response From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) Duration of Complete Response defined as time from start of first documented Complete Response \[CR\] to the time of disease progression or death, whichever occurs first. Only participants who have achieved complete response assessed by investigator were evaluated.
Number of Participants With Disease Control From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) Disease control includes CR (disappearance of all evidence of disease), PR (regression of measurable disease and no new sites), or SD for at least 8 weeks.
Terminal Half-Life (t1/2) of MEDI551 EOI of Cycle 1 Day 1; Pre-dose and EOI of C1D8, C2D1, C3D1 and C4D1 Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum.
Duration of Disease Control From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) Duration of disease control is defined as the time period from the start of disease control event to the event of disease progression.
Terminal Half-Life (t1/2) of MEDI0680 EOI of Cycle 1 Day 2; Pre-dose and EOI of C1D15, C2D1, C3D1 and C4D1 Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum.
Time to Response (TTR) From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) Time to response (TTR) defined as the time from the start of study drug administration until the first documentation of disease response. Only participants who have achieved objective response (confirmed CR or confirmed PR) assessed by investigator were evaluated for TTR.
Overall Survival (OS) From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) Overall survival defined as the time from the start of study drug administration until death due to any cause.
Number of Participants With Positive Anti-Drug Antibodies (ADA) for MEDI-551 and MEDI0680 30 min prior to infusion of MEDI-551 on Day 1 of Cycles 1, 2, 6, 9, and 12 and up to 90-days after last dose of study drug (up to approximately 2 years) 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.
Progression-free Survival (PFS) From treatment administration to 90-days after last dose of study drug (up to approximately 2 years) Progression-free survival (PFS) is defined as the time from the start of study drug administration until the first documentation of disease progression or death due to any cause, whichever occurs first.
Trial Locations
- Locations (1)
Research Site
🇺🇸Milwaukee, Wisconsin, United States