S1803, Phase III Study of Daratumumab/rHuPH20 (NSC-810307) + Lenalidomide or Lenalidomide as Post-Autologous Stem Cell Transplant Maintenance Therapy in Patients With Multiple Myeloma (MM) Using Minimal Residual Disease to Direct Therapy Duration (DRAMMATIC Study)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,100
- 试验地点
- 840
- 主要终点
- Overall Survival
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have completed ASCT within 180 days prior to registering to Step
- •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
- •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
- •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.
排除标准
- •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
- •(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/rHuPH
- •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).
研究组 & 干预措施
Arm 1: 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.
干预措施: Lenalidomide (Drug)
Arm 2: Lenalidomide + 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.
干预措施: Lenalidomide (Drug)
Arm 2: Lenalidomide + 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.
干预措施: Daratumumab/rHuPH20 (Drug)
Arm 1a: Continue 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.
干预措施: Lenalidomide (Drug)
Arm 2a: Continue Lenalidomide + 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.
干预措施: Lenalidomide (Drug)
Arm 2a: Continue Lenalidomide + 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.
干预措施: Daratumumab/rHuPH20 (Drug)
结局指标
主要结局
Overall Survival
时间窗: 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.
次要结局
- Response (PR or better)(From date of initial randomization until date of best response while on study treatment.)
- Progression Free Survival(From date of intial randomization until progression or death due to any cause, whichever occurs first, assessed up to 7 years)
- MRD Negativity(24 months from initial randomization)