A Study of Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly-Diagnosed Multiple Myeloma

Conditions

• Multiple Myeloma

Eligibility Criteria

Sex

ALL

Age

18 Years - 75 Years

Healthy Volunteers

Not accepted

Interventions

• Bortezomib — DRUG
  1.3 mg/m2 administered Subcutaneous (SC) or intravenous (IV) on days 1, 4, 8 and 11 of a 21 day treatment cycle for participants randomized to Arm A.
• Dexamethasone — DRUG
  20 mg or 40 mg per dose administered by mouth (PO) or IV. Participants randomized in Arm A: 20 mg/dose on days 1, 4, 8 and 11 on a 21 day treatment cycle; Participants randomized in Arm B: Cycles 1 through 8 - 40mg/dose on days 1, 8 and 15 on a 28-day cycle Participants randomized in Arm C: Cycle 1-2 - 40 mg/dose on days 1, 8, 15 and 22 on a 28-day cycle; Cycles 3-8 - 40mg/dose on Days 1, 8, 15 on a 28-day cycle;
• Lenalidomide — DRUG
  10 or 25 mg/day capsules administered PO. Participants randomized in Arm A: 25 mg/day capsules on Days 1 through 14 of a 21 day cycle.; Participants randomized in Arm B: Cycles 1 through 8 - 25 mg/day capsules on Days 1 through 21 of a 28 day cycle; Participants randomized in Arm C: Cycles 1 - 25 mg/day capsules on Days 2 through 21 of a 28 day cycle; Cycles 2 through 8 - 25 mg/day capsules on Days 1 through 21 of a 28 day cycle; Maintenance Therapy: 10 mg capsules on Days 1 through 21 on a 28 days cycle.
• Acetaminophen — DRUG
  650 mg administered PO. Participants randomized to Arm C: Cycles 1 through 8 - 650 mg administered on Days 1, 8 and 15.
• Diphenhydramine — DRUG
  25 mg administered via IV Participants randomized to Arm C: Cycles 1 through 8 - 25 mg administered on Days 1, 8 and 15.
• Montelukast — DRUG
  10 mg administered PO to participants randomized to Arm C prior to the first 4 doses of Daratumumab.
• Carfilzomib — DRUG
  20 mg or 56 mg/m2 per dose administered via IV. Participants randomized to Arm B: Cycle 1 - 20 mg/m2 per dose on Day 1 and 56 mg/m2 per dose on days 8 and 15 of a 28 day cycle; Cycles 2 through 8 - 56 mg/m2 per dose on days 1, 8 and 15 of a 28 day cycle; Participants randomized to Arm C: Cycle 1 - 20 mg/m2 per dose on Day 2 and 56 mg/m2 per dose on days 8 and 15 of a 28 day cycle; Cycles 2 through 8 - 56 mg/m2 per dose on days 1, 8 and 15 of a 28 day cycle
• Daratumumab — DRUG
  16 mg/kg administered via IV or 1800 mg SC, per treating physician discretion. Participants randomized to Arm C: Cycles 1 though 2 - 16 mg/kg IV or 1800 mg SC on days 1, 8, 15, and 22 of a 28 day cycle; Cycles 3 through 6- 16 mg/kg IV or 1800 mg SC on days 1 and 15 of a 28 day cycle; Cycles 7 through 8 - 16 mg/kg IV or 1800 mg SC on day 1 of a 28 day cycle
• Autologous Stem Cell Transplant (ASCT) — BIOLOGICAL
  Participants who are MRD positive at the conclusion of 8 cycles of study treatment, and were able to have their stem cells that were extracted, will receive ASCT from participants' bone marrow samples.

Study Details

This study is being done to find out whether carfilzomib, lenalidomide, and dexamethasone (KRD) or KRD and Daratumumab (KRD+DARA) might be safer and more effective ways of controlling multiple myeloma than the standard of care treatment, which is lenalidomide, bortezomib, and dexamethasone (VRD).

Key Dates

Start date

Feb 11, 2020

Status verified

Mar 2026

Primary completion

Feb 1, 2027

Completion

Feb 1, 2027

Study Design

Enrollment

310 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A - Bortezomib, Lenalidomide and Dexamethasone (VRD)
  Participants in this group will receive Bortezomib, Lenalidomide and Dexamethasone on a 21 day treatment cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.
• Experimental: Arm B - Carfilzomib, Lenalidomide and Dexamethasone (KRD)
  Participants in this group will receive Carfilzomib, Lenalidomide and Dexamethasone on a 28 day cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.
• Experimental: Arm C- Carfilzomib, Lenalidomide and Dexamethasone with Daratumumab (DKrd)
  Participants in this group will receive Carfilzomib, Lenalidomide, Dexamethasone with Daratumumab, Acetaminophen, Diphenhydramine and Montelukast on a 28 day cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.

Primary Outcome Measure

Rate of Minimal Residual Disease (MRD) Negativity [ Time Frame: Up to 32 weeks ]

Locations (7)

Find similar trials in Miami, FL

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