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
- 1,682
- 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
- •Registration Step 1 Except where otherwise indicated below that test is required in a shorter timeframe, all tests for establishing baseline disease status must be completed within 60 days prior to registration. All test results must be documented on the Baseline Tumor Assessment Form for Multiple Myeloma and the Onstudy Form.
- •Inclusion Criteria
- •Patients must have had a confirmed diagnosis of symptomatic multiple myeloma (See Section 4.1) that required systemic induction therapy prior to autologous stem cell transplantation (ASCT).
- •Patients with disease measurable by serum light chain assay alone are eligible (defined as >/= 100 mg/L on involved light chain).
- •Patients must be registered to Step 1 prior to registration to Step
- •Registration to Step 1 may take place prior to or after autologous stem cell transplant (ASCT), but after completion of induction therapy.
- •Patients must have initiated induction therapy within 12 months prior to registration Step 1 and have received at least two cycles of induction therapy.
- •Patients must be willing and able to take DVT prophylaxis (aspirin, low molecular weight heparin, warfarin, or equivalent oral anticoagulation).
- •Patients must be >/= 18 and /= 30 mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and Gault formula, or (2) serum creatinine < 2.5 mg/dL. Values must be obtained within 28 days prior to registration.
- •Patients must have adequate hepatic function defined by the following within 42 days prior to registration:
- •Total bilirubin \
排除标准
- •Patients with smoldering myeloma are not eligible. Patients with purely non-secretory MM as measured by electrophoresis and immunofixation and the absence of Bence Jones proteins in the urine are not eligible. Patients must have measurable M protein in the serum (defined as >/= 0.5g/dL) or urine (defined as >/= 200 mg/24h). Patients with plasma cell leukemia are not eligible.
- •Patients must not have any organ involvement by amyloidosis or evidence of amyloidosis related organ dysfunction.
- •Patients must not have progressive disease at any time prior to registration.
- •Patients must not be refractory to either lenalidomide or daratumumab/rHuPH
- •Patients must not be intolerant to either lenalidomide or daratumumab/rHuPH
- •Patients must not have received any investigational agents within 14 days prior to registration.
- •Patients must not have chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal. FEV1 is required for patients suspected of having chronic obstructive pulmonary disease and are not eligible if FEV1 is < 50% of predicted normal.
- •Patients must not have moderate or severe persistent asthma within the past 2 years and must not have currently uncontrolled asthma of any classification.
- •Patients must not have had prior autograft or allograft, or prior organ transplant requiring immunosuppressive therapy.
- •Patients must not have known allergy to any of the study drugs.
- •Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment are not eligible.
- •Patients must not have known central nervous system (CNS) involvement with multiple myeloma, defined as CSF positivity for plasma cells at any time or a parenchymal CNS plasmacytoma at time of enrollment. Lumbar puncture is not required.
- •Patients must not be seropositive for hepatitis C (except in the setting of sustained virologic response, defined as undetectable viral load at least 12 weeks after completion of antiviral therapy). HCV testing is only required if clinically indicated or if the patient has a history of HCV.
- •No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.
- •Patients must not have any uncontrolled intercurrent illness including (not limited to): Symptomatic CHF (NYHA III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 6 months prior to registration, Unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI CTCAE v5.0 Grade >/= 2), intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>/= Grade 3), or known psychiatric illness that would limit study compliance.
- •Registration Step 2 - First Randomization (Post-ASCT, Pre-Maintenance)
- •Inclusion Criteria:
- •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 /= 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 /= 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 \
研究组 & 干预措施
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 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 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)
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)
Study Entry / Screening
Study entry/screening to follow patient until Maintenance.
Arm 1b: Stop Lenalidomide
MRD- and randomized to Arm 1b: Discontinue protocol therapy.
Arm 2b: Stop Lenalidomide + Daratumumab/rHuPH20
MRD- and randomized to Arm 2b: Discontinue protocol therapy.
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 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)
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)