MRD-Guided Sequential Therapy For Deep Response in Newly Diagnosed Multiple Myeloma - MASTER-2 Trial
概览
- 阶段
- 2 期
- 干预措施
- Dara-VRd intensification, Dara-R maintenance
- 疾病 / 适应症
- Multiple Myeloma
- 发起方
- University of Alabama at Birmingham
- 入组人数
- 300
- 试验地点
- 18
- 主要终点
- Depth of response obtained with 6 cycles of Dara-VRd
- 状态
- 招募中
- 最后更新
- 3个月前
概览
简要总结
This research study will determine the proportion of patients with lowest minimal residual disease (MRD) response obtainable after receiving 6 cycles of study treatment. Minimal residual disease is multiple myeloma cells below the level of 1 cancer cell out of 100,000 in the bone marrow.
For patients who become MRD "negative" (i.e. less than 1 cancer cell out of 100,000) at the end of 6 cycles of therapy, this study will study if that good response can be maintained with 3 additional cycles of treatment instead of use of autologous hematopoietic cell transplantation (AHCT).
For patients who are MRD "positive" at the end of 6 cycles of therapy, this study will answer whether more patients can become and remain MRD "negative" with AHCT plus teclistamab in combination with daratumumab when compared with patients who undergo AHCT followed by lenalidomide (an established anti-myeloma drug) plus daratumumab.
研究者
Luciano Jose Costa, MD
Professor of Medicine
University of Alabama at Birmingham
入排标准
入选标准
- •Age\>18 years with no upper age limit
- •Newly diagnosed multiple myeloma with indication for initiation of therapy.
- •ECOG performance status 0-2
- •No prior MM-directed therapy except for dexamethasone (up to 160 mg) and/or bortezomib (up to 5.2 mg/m2) and/or cyclophosphamide up to 1000 mg/m2 and/or lenalidomide (up to 21 days of therapy) administered for no longer than 4 weeks prior to enrollment (pre induction). If subject received any prior therapy, pretreatment parameters necessary for disease characterization and response assessment must be available.
- •Measurable disease meeting at least one of the following criteria (at screening or prior to pre induction):
- •Serum monoclonal (M) protein ≥1.0 g/dl (≥0.5 g/dl if IgA, IgD, IgE or IgM multiple myeloma)
- •≥ 200 mg of M protein/24h in the urine
- •Difference between affected and unaffected free light chain ≥10 mg/dL with abnormal kappa to lambda ratio.
- •Have clinical laboratory values meeting the following criteria during the Screening Phase and also at start of administration of study treatment
- •Hemoglobin ≥7 g/dL (≥4.65 mmol/L; without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted)
排除标准
- •Diagnosis of Plasma cell leukemia, primary light chain amyloidosis, POEMS, or Waldenstrom's macroglobulinemia.
- •Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the teclistamab Investigator's Brochure and appropriate package inserts)
- •Prior or concurrent exposure to any of the following:
- •Teclistamab or any anti-BCMA therapy
- •Daratumumab or any anti-CD38 therapy
- •Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or ≥5 half-lives, whichever is less
- •Investigational vaccine within 4 weeks
- •Live, attenuated vaccine within 4 weeks before randomization.
- •Radiotherapy within 14 days or focal radiation within 7 days
- •Gene-modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, NK cells) within 3 months
研究组 & 干预措施
Arm A
3 cycles of Dara-VRd intensification followed by 13 cycles of Dara-R maintenance in MRD negative patients
干预措施: Dara-VRd intensification, Dara-R maintenance
Arm B
AHCT intensification followed by 13 cycles of Dara-R maintenance in MRD negative patients
干预措施: AHCT intensification, Dara-R maintenance
Arm C
AHCT intensification, 3 cycles of Dara-Tec consolidation and 13 cycles of Dara-Tec maintenance in MRD positive patients
干预措施: AHCT intensification, Tec-Dara consolidation, Tec-Dara maintenance
Arm D
AHCT intensification, 3 cycles of Dara-R consolidation and 13 cycles of Dara-R maintenance in MRD positive patients
干预措施: AHCT intensification, Dara-R consolidation, Dara-R maintenance
Arm M
Induction - 6 cycles of Dara-VRd in all participants
干预措施: Dara-VRd induction
结局指标
主要结局
Depth of response obtained with 6 cycles of Dara-VRd
时间窗: 6 months
For the primary objective "for all patients" to describe the depth of response obtained with 6 cycles of Dara-VRd and the corresponding endpoint of MRD negativity at end of induction all patients with MRD evaluable
Sustained MRD negativity
时间窗: 18 months
MRD \<10-5 assessed before and after 13 cycles of maintenance
次要结局
- Progression-free survival(60 months)
- Cumulative incidence of MRD resurgence or progression(60 months)
- Overall Survival(60 months)