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Iberdomide, Daratumumab, Carfilzomib, and Dexamethasone (Iber-KDd) in Patients With Relapsed/Refractory Multiple Myeloma

ConditionsRefractory Multiple MyelomaRelapsed Multiple Myeloma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorBenjamin T Diamond, MD

About this trial

The investigators want to find out whether or not giving patients who have relapsed or refractory multiple myeloma (MM) the experimental medication combination iberdomide, carfilzomib, daratumumab, and dexamethasone (Iber-KDd) may produce better results than the current (standard of care) treatments. This study will examine the tolerability and efficacy of this combination therapy for all participants and the ability of this combination therapy to shrink or prevent MM from returning.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Serum monoclonal protein ≥ 1.0 g/dL

Urine monoclonal protein ≥ 200 mg/24 hour

Involved serum immunoglobulin free light chains (FLC) ≥ 10 mg/dL AND abnormal kappa/lambda ratio.

Best response achieved during CD38-directed therapy was ≥ PR.

Disqualifiers

Treatment of hypercalcemia or spinal cord compression or aggressively progressing myeloma with current or prior corticosteroids is permitted.

Patients may receive kyphoplasty/vertebroplasty for symptomatic vertebral compression fractures.

Bone targeting agents are permitted.

Concurrent or prior treatment with corticosteroids for indications other than MM is permitted.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Iberdomide

    Drug

    Participants will receive Iberdomide (Iber) therapy orally (PO) in capsules as follows: * Combination therapy: Cycles 1 to 8: 1 mg per day\*, Days 1 to 21 every 28 days. * Monotherapy: Cycles 9 to 20: 1 mg per day\*, Days 1 to 21 every 28 days. (\*) The first 6 patients will begin at 1 mg/day as lead-in with option to increase to 1.3 mg with dose-escalation cohort after two (2) cycles tolerated therapy

  • Carfilzomib

    Drug

    Participants will receive Carfilzomib (K) therapy intravenously (IV) as follows: * Cycle 1: 20 mg/m2 per dose on Day 1; 56 mg/m2 per dose on Days 8 and 15 * Cycles 2 to 8: 56 mg/m2 per dose on Days 1, 8, and 15.

  • Daratumumab

    Drug

    Participants will receive Daratumumab (D) therapy subcutaneously (SC) or intravenously (IV) as follows: * Cycles 1 and 2: 1800 mg SC or 16 mg/kg IV on Days 1, 8, 15, and 22 * Cycles 3 through 6: 1800 mg SC or 16 mg/kg IV on Days 1 and 15 * Cycles 7 and 8: 1800 mg SC or 16 mg/kg IV on Day 1.

  • Dexamethasone

    Drug

    Participants will receive Dexamethasone (d) therapy either orally (PO) or intravenously (IV) as follows: * Cycles 1 and 2: 40 mg/dose on Days 1, 8, and 15; 20 mg/dose on Day 22 * Cycles 3 and 4: 40 mg/dose on Days 1, 8, and 15 * Cycles 5 through 8: 20 mg/dose on Days 1, 8, and 15.

  • Acetaminophen

    Drug

    Participants will receive Acetaminophen orally (PO) prior to Iber-KDd therapy as follows: * Cycles 1 and 2: 650 mg/dose on Days 1, 8, 15, and 22 * Cycles 3 through 6: 650 mg/dose on Days 1 and 15 * Cycles 7 and 8: 650 mg/dose on Day 1.

  • Diphenhydramine

    Drug

    Participants will receive Diphenhydramine either orally (PO) or intravenously (IV) prior to Iber-KDd therapy as follows: * Cycles 1 and 2: 25 mg/dose on Days 1, 8, 15, and 22 * Cycles 3 through 6: 25 mg/dose on Days 1 and 15 * Cycles 7 and 8: 25 mg/dose on Day 1.

  • Montelukast

    Drug

    Participants will receive Montelukast orally (PO) prior to Iber-KDd as follows: * Cycle 1 only: 10 mg/dose, Days 1, 8, 15, and 22, to be administered prior to the first 4 doses of Daratumumab (D).

Treatment groups

30 Participants
are divided into 2 treatment groups
Group A: Iber-KDd Combination TherapyExperimental treatment 7 interventions
Group B: Iber MonotherapyExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Rate of MRD-negativity: Iber-KDd Combination therapy.

The rate of minimal residual disease negativity (MRD-negativity) will be reported as the number of participants achieving MRD-negativity after eight cycles of Iber-KDd combination therapy. MRD-negativity is defined as less than one (\<1) residual cancer cell detected in 100,000 cells assessed.

Time frame
Up to 8 months

Secondary outcomes

1

Number of Participants Experiencing Treatment-Related Toxicity After Starting Iber-KDd Combination Therapy

The safety and tolerability of Iber-KDd combination therapy will be assessed and reported as the number of participants experiencing treatment-related toxicity after start of combination therapy, including treatment-related adverse events (AEs) and serious adverse events (SAEs). AEs and SAEs will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5, per physician discretion.

Time frame
Up to 9 months
2

Best Response: Iber-KDd Combination Therapy

Best response will be reported as the proportion of participants achieving their greatest response to Iber-KDd combination therapy as follows: Partial response (PR) or better, very good partial response (VGPR) or better, complete response (CR), and stringent complete response (sCR). Response will be assessed using the International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma.

Time frame
Up to 8 months
3

Overall Response Rate (ORR): Iber-KDd Combination Therapy

Overall response rate (ORR) is defined as the number of participants achieving partial response (PR), very good partial response (VGFR)m complete response (CR) or stringent complete response (sCR) to Iber-KDd combination therapy. Response will be assessed using the International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma.

Time frame
Up to 8 months
4

Best Response: Iber Monotherapy

Best response will be reported as the proportion of participants achieving their greatest response to Iberdomide monotherapy as follows: Partial response (PR) or better, very good partial response (VGPR) or better, complete response (CR), and stringent complete response (sCR). Response will be assessed using the International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma.

Time frame
Up to 20 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Benjamin T Diamond, MD

Lead sponsor

University of Miami

Sponsor institution

Bristol-Myers Squibb

Collaborator

Source ClinicalTrials.gov
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