S1803, Lenalidomide +/- Daratumumab/rHuPh20 as Post-ASCT Maintenance for MM w/MRD to Direct Therapy Duration
- Registration Number
- NCT04071457
- Lead Sponsor
- SWOG Cancer Research Network
- Brief Summary
Patients are enrolled to screening (Reg Step 1) prior to or after ASCT but prior to Reg Step 2. Patients are followed until they will begin Maintenance and then registered to Reg Step 2 (first randomization). Patients are randomized between Lenalidomide for 2 years and Lenalidomide + Daratumumab/rHuPH20. After 2 years of Maintenance, MRD is assessed to guide further therapy. MRD-positive patients will continue with the assigned treatment. MRD-negative patients will be further randomized (Reg Step 3) to either continue or discontinue the assigned treatment. Patients are treated for up to 7 years from Step 2 reg and followed for up to 15 years.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1100
- Patients must have completed ASCT within 180 days prior to registering to Step 2.
- Patients must have one of the following performed within 60 days prior to registration for disease assessment: diagnostic quality skeletal survey, whole body CT scan, MRI, or PET.
- Patients must have Zubrod Performance Status </= 2
- Patients must have adequate bone marrow function as evidenced by platelets >/= 75,000/mm3 and ANC >/= 1,000/mm3 within 28 days prior to first randomization:
- Patients must have adequate hepatic function defined by the following within 28 days prior to first randomization:
- Total bilirubin </=1.5 x IULN (institutional upper limit of the norm) AND AST and ALT </=3.0 x IULN
- Patients must have evidence of adequate renal function, as defined by creatinine clearance (CrCl) >/= 30 mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and Gault formula, or have a serum creatinine < 2.5 mg/dL within 28 days prior to first randomization.
- All ASCT-related toxicities must have recovered to </=Grade 1 (except for alopecia, fatigue and amenorrhea) prior to first randomization.
- Mucositis and gastrointestinal symptoms must have resolved to </=Grade 1.
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to registration.
- FCBP must agree to have a second pregnancy test within 24 hours prior to starting Cycle 1. Further, FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide. FCBP must also agree to ongoing pregnancy testing and must agree to not become pregnant for at least 3 months after the last dose of study treatment.
- Men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy, during the study treatment and for 3 months after the last dose of study treatment.
- Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
- Patients must not have received any other maintenance therapy post-ASCT and prior to Step 2 registration.
- Patients must not have had progressive disease between induction and registration to Registration Step 2. (See Section 10.1b).
Registration Step 3 - Second Randomization (Post 24 Months Maintenance)
Inclusion Criteria:
- Patients must have completed 24 cycles of protocol maintenance with either lenalidomide or lenalidomide + daratumumab/rHuPH20.
- Patients must have 24-month MRD by NGS test results available and must be MRD negative. Patients whose PCR results are indeterminable will be considered to have positive results.
- Patients must be in very good partial remission (VGPR) or better by IMWG response criteria (see Section 10.1b).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2a: Continue Lenalidomide + Daratumumab/rHuPH20 Daratumumab/rHuPH20 MRD+ or MRD- and randomized to Arm 2a: Lenalidomide 10 mg/day, D1-28, q28 days for 3 cycles, then 15 mg/day, D1-28 for up to 7 years from starting treatment. Plus Daratumumab/rHuPH20 1800 mg/30,000 units D1, 8, 15, 22 q 28 days for 2 cycles, then D 1 and 15 q 28 days for cycles 3-6 then D1 q 28 days for subsequent cycles for up to 7 years from starting treatment. Arm 1: Lenalidomide Lenalidomide Lenalidomide 10 mg/day, D1-28, q28 days for 3 cycles, then 15 mg/day, D1-28 for up to 2 years from starting treatment. Arm 2: Lenalidomide + Daratumumab/rHuPH20 Daratumumab/rHuPH20 Lenalidomide 10 mg/day, D1-28, q28 days for 3 cycles, then 15 mg/day, D1-28 for up to 2 years from starting treatment. Plus Daratumumab/rHuPH20 1800 mg/30,000 units D1, 8, 15, 22 q 28 days for 2 cycles, then D 1 and 15 q 28 days for cycles 3-6 then D1 q 28 days for subsequent cycles for up to 2 years from starting treatment. Arm 2: Lenalidomide + Daratumumab/rHuPH20 Lenalidomide Lenalidomide 10 mg/day, D1-28, q28 days for 3 cycles, then 15 mg/day, D1-28 for up to 2 years from starting treatment. Plus Daratumumab/rHuPH20 1800 mg/30,000 units D1, 8, 15, 22 q 28 days for 2 cycles, then D 1 and 15 q 28 days for cycles 3-6 then D1 q 28 days for subsequent cycles for up to 2 years from starting treatment. Arm 1a: Continue Lenalidomide Lenalidomide MRD+ or MRD- and randomized to Arm 1a: Lenalidomide 10 mg/day, D1-28, q28 days for 3 cycles, then 15 mg/day, D1-28 for up to 7 years from starting treatment. Arm 2a: Continue Lenalidomide + Daratumumab/rHuPH20 Lenalidomide MRD+ or MRD- and randomized to Arm 2a: Lenalidomide 10 mg/day, D1-28, q28 days for 3 cycles, then 15 mg/day, D1-28 for up to 7 years from starting treatment. Plus Daratumumab/rHuPH20 1800 mg/30,000 units D1, 8, 15, 22 q 28 days for 2 cycles, then D 1 and 15 q 28 days for cycles 3-6 then D1 q 28 days for subsequent cycles for up to 7 years from starting treatment.
- Primary Outcome Measures
Name Time Method Overall Survival From date of intial randomization until death due to any cause, assessed up to 15 years Overall survival will evaluated using a weighted log-rank test and will be compared between primary treatment arms. All eligible patients with valid consent will be included in the analysis. Patients last known to be alive are censored at the date of last contact.
- Secondary Outcome Measures
Name Time Method Response (PR or better) From date of initial randomization until date of best response while on study treatment. Per International Uniform Response Criteria for Multiple Myeloma PR- ≥ 50% reduction in size of soft tissue plasmacytomas \& plasma cells; ≥ 50% decrease in serum \& reduction in urine M protein ≥ 90% or to \< 200 mg/24hr or ≥ 50% decrease in difference in uninvolved \& involved serum free light chain levels; VGPR- PR + Serum and urine M proteins detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M protein \& urine M protein \< 100 mg/24 hrs; uPR- 1 objective status of PR, but confirmation studies are not done, or do not meet the requirements necessary to confirm response; SD- does not meet criteria for sCR, CR, VGPR, PR or PROG; PROG- new or increase in size of existing bone lesions or soft tissue plasmacytomas/ development of hypercalcemia attributable solely to MM/ ≥ 25% increase from baseline/ lowest response level of either serum or Urine M protein, difference in involved \& uninvolved serum free light chain level or bone marrow plasma cell percentage.
Progression Free Survival From date of intial randomization until progression or death due to any cause, whichever occurs first, assessed up to 7 years Progression-free survival will evaluated using a weighted log-rank test and will be compared between primary treatment arms. All eligible patients with valid consent will be included in the analysis. Patients last known to be progression-free and alive are censored at the date of last contact.
MRD Negativity 24 months from initial randomization The rate of MRD response will be calculated as the number of patients who achieved MRD response divided by the number of eligible patients; patients without a conclusive MRD results will be included as non-responders. Comparisons between arms will be made using a stratified Cochran-Mantel-Haenszel test.
MRD data will be collected from the central testing laboratory, including percent of cells detected and total cells collected. Unless the sample is limiting, 5 x 106 events are collected for a standard multiple myeloma MRD sensitivities of 0.0001%.
MRD negativity will be defined as no templates observed at a sensitivity of 1 in a million cells assessed, with a minimum of 1 million cells being assessed.
MRD positivity will be defined as any templates observed regardless of the number of cells analyzed, or non-diagnostic specimens, including if the reference specimen from diagnosis is not able to be sequenced.
Trial Locations
- Locations (840)
Anchorage Associates in Radiation Medicine
🇺🇸Anchorage, Alaska, United States
Anchorage Radiation Therapy Center
🇺🇸Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
🇺🇸Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
🇺🇸Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸Anchorage, Alaska, United States
Katmai Oncology Group
🇺🇸Anchorage, Alaska, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
Fairbanks Memorial Hospital
🇺🇸Fairbanks, Alaska, United States
Kingman Regional Medical Center
🇺🇸Kingman, Arizona, United States
Scroll for more (830 remaining)Anchorage Associates in Radiation Medicine🇺🇸Anchorage, Alaska, United StatesSite Public ContactContact907-212-6871AKPAMC.OncologyResearchSupport@providence.orgCharles W. DrescherPrincipal Investigator