An Open-label, Multicenter, Phase 2 Trial Investigating the Efficacy and Safety of Daratumumab in Subjects With Multiple Myeloma Who Have Received at Least 3 Prior Lines of Therapy (Including a Proteasome Inhibitor and IMiD) or Are Double Refractory to a Proteasome Inhibitor and an IMiD
Overview
- Phase
- Phase 2
- Intervention
- Daratumumab 16 mg/kg (Part 1)
- Conditions
- Multiple Myeloma
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 124
- Primary Endpoint
- Percentage of Participants With Overall Response
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of 2 daratumumab treatment regimens in participants with multiple myeloma who have received at least 3 prior lines of therapy (including a proteasome inhibitor [PI] and immunomodulatory drug [IMiD]) or are double refractory to a PI and an IMiD.
Detailed Description
This is an open-label (identity of assigned study drug will be known) study of daratumumab for the treatment of participants with multiple myeloma who have received at least 3 prior lines of therapy including a PI and an IMiD or whose disease is double refractory to both a PI and an IMiD. Up to approximately 150 participants are to be enrolled. The study includes screening, treatment, and follow-up phases. Participants will receive daratumumab by intravenous infusion (28-day cycles) until disease progression, unacceptable toxicity, or other protocol-defined reasons. For all study drug administrations, participants will receive pre- and post-infusion medications for the prevention of infusion related reactions. Follow-up will continue until death, loss to follow up, consent withdrawal for study participation, or study end, whichever occurs first. The study will consist of 2 sequential parts (Part 1 and Part 2). The purpose of Part 1 is to select a dose and schedule for Part 2 of the study. Assessment of tumor response and disease progression will be conducted according to IMWG response criteria. Serial pharmacokinetic blood samples and a pharmacogenomic blood sample will be collected. Safety will be monitored throughout the study. At the end of the study, participants who are benefiting from treatment with daratumumab will have the option to continue treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Documented multiple myeloma according to protocol-defined criteria
- •Evidence of disease progression on the most recent prior treatment regimen based on International Myeloma Working Group criteria
- •Eastern Cooperative Oncology Group performance status score of 0, 1, or 2
- •Laboratory values and electrocardiogram within protocol-defined parameters at screening
Exclusion Criteria
- •Received daratumumab or other anti-CD38 therapies previously
- •Nonsecretory multiple myeloma
- •Previously received an allogenic stem cell transplant or has received an autologous stem cell transplantation within 12 weeks
- •Exhibiting clinical signs of meningeal involvement of multiple myeloma
- •Known chronic obstructive pulmonary disease, persistent asthma, or a history of asthma within 5 years
- •Seropositive for human immunodeficiency virus, hepatitis B or antibodies to hepatitis B surface and core antigens, or hepatitis C
- •Has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis
Arms & Interventions
Part 1
During Stage 1 of Part 1, participants will be randomized to receive daratumumab treatment regimens in Group A and Group B. If in Stage 1, 1 or both of the treatment groups is considered to be ineffective and/or not well tolerated, then that treatment group will be terminated. Participants in Group B will be given the option to cross over to Group A if the investigator deems it in the best interest of the participants.
Intervention: Daratumumab 16 mg/kg (Part 1)
Part 1
During Stage 1 of Part 1, participants will be randomized to receive daratumumab treatment regimens in Group A and Group B. If in Stage 1, 1 or both of the treatment groups is considered to be ineffective and/or not well tolerated, then that treatment group will be terminated. Participants in Group B will be given the option to cross over to Group A if the investigator deems it in the best interest of the participants.
Intervention: Daratumumab 8 mg/kg (Part 1)
Part 1
During Stage 1 of Part 1, participants will be randomized to receive daratumumab treatment regimens in Group A and Group B. If in Stage 1, 1 or both of the treatment groups is considered to be ineffective and/or not well tolerated, then that treatment group will be terminated. Participants in Group B will be given the option to cross over to Group A if the investigator deems it in the best interest of the participants.
Intervention: Methylprednisolone
Part 1
During Stage 1 of Part 1, participants will be randomized to receive daratumumab treatment regimens in Group A and Group B. If in Stage 1, 1 or both of the treatment groups is considered to be ineffective and/or not well tolerated, then that treatment group will be terminated. Participants in Group B will be given the option to cross over to Group A if the investigator deems it in the best interest of the participants.
Intervention: Acetaminophen
Part 1
During Stage 1 of Part 1, participants will be randomized to receive daratumumab treatment regimens in Group A and Group B. If in Stage 1, 1 or both of the treatment groups is considered to be ineffective and/or not well tolerated, then that treatment group will be terminated. Participants in Group B will be given the option to cross over to Group A if the investigator deems it in the best interest of the participants.
Intervention: Diphenhydramine
Part 2
Based on the Part 1 response rate, Group A or B daratumumab treatment will be selected as the treatment regimen for participants enrolled in Part 2.
Intervention: Methylprednisolone
Part 2
Based on the Part 1 response rate, Group A or B daratumumab treatment will be selected as the treatment regimen for participants enrolled in Part 2.
Intervention: Acetaminophen
Part 2
Based on the Part 1 response rate, Group A or B daratumumab treatment will be selected as the treatment regimen for participants enrolled in Part 2.
Intervention: Diphenhydramine
Part 2
Based on the Part 1 response rate, Group A or B daratumumab treatment will be selected as the treatment regimen for participants enrolled in Part 2.
Intervention: Daratumumab (Part 2)
Outcomes
Primary Outcomes
Percentage of Participants With Overall Response
Time Frame: Up to 14.4 Months
Overall response defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Per IMWG criteria, sCR: is defined as normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5 % plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \>= 90% reduction in serum M-protein plus urine M-protein level \< 100mg/24 hours; PR: \>= 50 % reduction of serum M-protein and reduction in 24 hour urinary M-protein by \>= 90% or to \<200 mg/24 hours; if the serum and urine M-protein are not measurable, a decrease of \>=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria.
Secondary Outcomes
- Time to Disease Progression(Up to 14.4 Months)
- Time to Response(Up to 14.4 Months)
- Overall Survival(Approximately up to 3 years)
- Progression Free Survival(Up to 14.4 Months)
- Duration of Response(Up to 14.4 Months)
- Percentage of Participants With Clinical Benefit(Up to 14.4 Months)