A Study to Evaluate Subcutaneous TAK-079 Added to Standard of Care Regimens in Participants With Newly Diagnosed Multiple Myeloma (NDMM)
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT03984097
- Lead Sponsor
- Takeda
- Brief Summary
The purpose of this original study is to determine the recommended phase 2 dose (RP2D) of TAK-079 when administered to participants with NDMM in combination with the backbone treatment regimen. The purpose of the safety/access cohort is to provide continued access to TAK-079 to participants previously enrolled to a TAK-079 parent study and to evaluate the long-term safety profile of TAK-079.
- Detailed Description
Treatment phase drug being tested in this study is called TAK-079. TAK-079 is being tested to evaluate the safety, tolerability, efficacy, and pharmacokinetic (PK) when added to 1 of 2 standard backbone regimens (LenDex or VRd) with newly diagnosed NDMM for whom stem cell transplantation (SCT) is not planned as initial therapy.
The study will enroll approximately 36 participants. Participants will be non-randomly assigned to one of the two treatment groups in the original study or Treatment Phase:
* TAK-079 and LenDex
* TAK-079 and VRd
All enrolled participants will have the opportunity to complete the treatment therapy and then enter the Extension study for as long as participants continue to derive benefit. Safety Extension Phase participants who have previously received and tolerated TAK-079-based parent study will continue to the extension study. The study will also evaluate the long-term safety profile of TAK-079. Participants will continue to receive TAK-079 and, if applicable, SOC backbone therapy as per the parent study.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Safety Extension Phase: TAK-079 and, if applicable, backbone therapy (LenDex, VRd, or PomDex) Dexamethasone TAK-079 dosing and, if applicable, backbone therapy will be administered as per the schedule outlined in the parent study. Safety Extension Phase: TAK-079 and, if applicable, backbone therapy (LenDex, VRd, or PomDex) Bortezomib TAK-079 dosing and, if applicable, backbone therapy will be administered as per the schedule outlined in the parent study. Treatment Phase: TAK-079 and VRd Pomalidomide TAK-079 subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with bortezomib, subcutaneously, once on Days 1, 8, and 15, for a maximum of 8 cycles, lenalidomide, orally, once daily for 21 days, and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until PD or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to 2 years. The dosage of dexamethasone can be reduced for participants who are \>75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy. Safety Extension Phase: TAK-079 and, if applicable, backbone therapy (LenDex, VRd, or PomDex) Lenalidomide TAK-079 dosing and, if applicable, backbone therapy will be administered as per the schedule outlined in the parent study. Treatment Phase: TAK-079 and LenDex Pomalidomide TAK-079, subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with lenalidomide, orally, once daily for 21 days and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until progressive disease (PD) or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to 2 years. The dosage of dexamethasone can be reduced for participants who are greater than (\>) 75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy. Safety Extension Phase: TAK-079 and, if applicable, backbone therapy (LenDex, VRd, or PomDex) Pomalidomide TAK-079 dosing and, if applicable, backbone therapy will be administered as per the schedule outlined in the parent study. Treatment Phase: TAK-079 and VRd Dexamethasone TAK-079 subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with bortezomib, subcutaneously, once on Days 1, 8, and 15, for a maximum of 8 cycles, lenalidomide, orally, once daily for 21 days, and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until PD or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to 2 years. The dosage of dexamethasone can be reduced for participants who are \>75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy. Treatment Phase: TAK-079 and LenDex TAK-079 TAK-079, subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with lenalidomide, orally, once daily for 21 days and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until progressive disease (PD) or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to 2 years. The dosage of dexamethasone can be reduced for participants who are greater than (\>) 75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy. Safety Extension Phase: TAK-079 and, if applicable, backbone therapy (LenDex, VRd, or PomDex) TAK-079 TAK-079 dosing and, if applicable, backbone therapy will be administered as per the schedule outlined in the parent study. Treatment Phase: TAK-079 and VRd TAK-079 TAK-079 subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with bortezomib, subcutaneously, once on Days 1, 8, and 15, for a maximum of 8 cycles, lenalidomide, orally, once daily for 21 days, and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until PD or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to 2 years. The dosage of dexamethasone can be reduced for participants who are \>75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy. Treatment Phase: TAK-079 and LenDex Lenalidomide TAK-079, subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with lenalidomide, orally, once daily for 21 days and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until progressive disease (PD) or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to 2 years. The dosage of dexamethasone can be reduced for participants who are greater than (\>) 75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy. Treatment Phase: TAK-079 and LenDex Dexamethasone TAK-079, subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with lenalidomide, orally, once daily for 21 days and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until progressive disease (PD) or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to 2 years. The dosage of dexamethasone can be reduced for participants who are greater than (\>) 75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy. Treatment Phase: TAK-079 and VRd Lenalidomide TAK-079 subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with bortezomib, subcutaneously, once on Days 1, 8, and 15, for a maximum of 8 cycles, lenalidomide, orally, once daily for 21 days, and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until PD or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to 2 years. The dosage of dexamethasone can be reduced for participants who are \>75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy. Treatment Phase: TAK-079 and VRd Bortezomib TAK-079 subcutaneously, once weekly for 8 weeks, then once every 2 weeks for 16 weeks, and then once every 4 weeks thereafter, along with bortezomib, subcutaneously, once on Days 1, 8, and 15, for a maximum of 8 cycles, lenalidomide, orally, once daily for 21 days, and dexamethasone, orally or intravenously, once on Days 1, 8, 15 and 22 in each 28-day treatment until PD or unacceptable toxicity, withdrawal of consent, death, or termination of the study by sponsor for up to 2 years. The dosage of dexamethasone can be reduced for participants who are \>75 years, have poorly controlled diabetes, or had prior intolerance to or AE from corticosteroid therapy.
- Primary Outcome Measures
Name Time Method Treatment Phase: RP2D of TAK-079 Up to Cycle 1 (Cycle length is equal to [=] 28 days) RP2D of TAK-079 along with lenalidomide-dexamethasone (LenDex) or TAK-079 along with bortezomib, lenalidomide, and dexamethasone (VRd) will be based on number of participants with dose limiting toxicity (DLT). DLTs will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Safety Extension Phase: Number of Participants Who Require Dose Modification From first dose up to 30 days after the last dose of study drug (up to 4 years) Safety Extension Phase: Number of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs) From first dose up to 30 days after the last dose of study drug (up to 4 years) Adverse event (AE) Grades will be evaluated as per NCI CTCAE, version 4.03.
Safety Extension Phase: Number of Participants With TEAEs Leading to Treatment Discontinuation From first dose up to 30 days after the last dose of study drug (up to 4 years) Safety Extension Phase: Number of Participants Reporting one or More Serious Adverse Events (SAEs) From first dose up to 30 days after the last dose of study drug (up to 4 years)
- Secondary Outcome Measures
Name Time Method Treatment Phase: Overall Response Rate (ORR) Up to 2 years ORR based on International Myeloma Working Group (IMWG) Uniform Response Criteria, is defined as the percentage of participants who achieved a PR or better during the study. PR is defined as greater than or equal to (\>=) 50 percent (%) reduction of serum M-protein, and reduction in 24-hour urinary M-protein by \>=90% or to less than (\<) 200 milligram per 24 hours (mg/24 h). If serum and urine M protein are not measurable, \>=50% decrease in difference between involved and uninvolved free light chain (FLC) levels is required in place of M protein criteria.
Treatment Phase: Number of Participants with TEAEs Leading to Treatment Discontinuation From first dose up to 30 days after the last dose of study drug (up to 2 years) Treatment Phase: Number of Participants Reporting one or More TEAEs and SAEs From first dose up to 30 days after the last dose of study drug (up to 2 years) Treatment Phase: Number of Participants With Grade 3 or Higher TEAEs From first dose up to 30 days after the last dose of study drug (up to 2 years) AE Grades will be evaluated as per NCI CTCAE, version 4.03.
Treatment Phase: Number of Participants With AEs Leading to On-study Deaths From screening up to 30 days after the last dose of study drug (up to 2 years)
Trial Locations
- Locations (9)
American Oncology Partners of Maryland, PA
🇺🇸Bethesda, Maryland, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Pacific Cancer Care
🇺🇸Monterey, California, United States
Alabama Oncology
🇺🇸Birmingham, Alabama, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Good Samaritan Hospital
🇺🇸Cincinnati, Ohio, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Froedtert Hospital & the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States