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

NCT05896228 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20230227
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Relapsed Multiple Myeloma; Refractory Multiple Myeloma

Outcome Measures

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.

  Up to 8 months

Secondary Outcomes (12)

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

  Up to 9 months

• Best Response: Iber-KDd Combination Therapy

  Up to 8 months

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

  Up to 8 months

• Best Response: Iber Monotherapy

  Up to 20 months

• Overall Response Rate (ORR): Iber Monotherapy

  Up to 20 months

Study Arms (2)

Iber-KDd Combination Therapy

EXPERIMENTAL

Prior to Iber-KDd combination therapy, participants will receive Acetaminophen, Diphenhydramine and Montelukast therapy per protocol. Participants will receive up to eight (8) 28-day cycles of combination Iberdomide (I), Carfilzomib (K), Daratumumab (D), and Dexamethasone (d) (Iber-KDd) therapy. Participants will receive Iber-KDd combination therapy for approximately 8 months. In the absence of disease progression, participants will continue on to Iber monotherapy. Participants with disease progression will discontinue study therapy but will continue to be followed for up to three (3) years after conclusion of Iber-KDd combination therapy.

Drug: Iberdomide; Drug: Carfilzomib; Drug: Daratumumab; Drug: Dexamethasone; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Montelukast

Iber Monotherapy

EXPERIMENTAL

After completion of Iber-KDd combination therapy, and In the absence of disease progression, participants will then receive up to twelve (12) 28-day cycles of Iberdomide (Iber) monotherapy. Participants will receive Iber monotherapy for up to 12 months or until disease progression. Participants will be followed for up to three (3) years after conclusion of Iber monotherapy. Total study participation is up to five (5) years.

Drug: Iberdomide

Interventions

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

Iber Monotherapy; Iber-KDd Combination 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.

Iber-KDd Combination Therapy

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.

Iber-KDd Combination Therapy

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.

Iber-KDd Combination Therapy

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.

Iber-KDd Combination Therapy

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.

Iber-KDd Combination Therapy

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).

Iber-KDd Combination Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed MM with progressive disease according to the IMWG criteria 47 during or within 60 days of their last regimen who have received 1-3 lines of prior therapy (inclusive of a lenalidomide-containing regimen) and have measurable disease within 4 weeks of enrollment based on one of the following:
• 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.
• Note: Because the primary endpoint is MRD-negativity rate, per the discretion of the Principal Investigator (PI), patients without measurable disease (e.g., M-spike \< 1.0 g/dL) may also be enrolled in line with the IMWG MM response criteria 47.
• Prior treatment with cluster of differentiation 38 (CD38) -directed therapy is permitted only if all the following are fulfilled:
• Best response achieved during CD38-directed therapy was ≥ PR.
• Patient did not progress while receiving CD38-directed therapy or within 60 days of last dose of therapy.
• Patient did not discontinue CD38-directed therapy due to a related AE.
• Prior treatment with carfilzomib is permitted only if all the following are fulfilled:
• Best response achieved during carfilzomib-based therapy was ≥ PR.
• Patient did not progress while receiving carfilzomib-based therapy or within 60 days of last dose of therapy.
• Patient did not discontinue carfilzomib due to a related AE.
• Creatinine Clearance (CrCl) ≥60 ml/min measured within 4 weeks of enrollment. CrCl can be measured or estimated using Cockcroft-Gault method, Modification of Diet in Renal Disease (MDRD), or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae.
• Age ≥ 18 years at the time of signing the informed consent documentation. Age limit of 75 years.

You may not qualify if:

• Patients receiving concurrent systemic treatment for MM with the following exceptions:
• 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.
• Focal radiation therapy within 14 days prior to randomization with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma.
• Prior MM treatments must be concluded with a washout period of 2 weeks from last dose.
• Patients who are refractory to an anti-CD38-directed regimen:
• Patients with plasma cell leukemia.
• Patients with Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes syndrome (POEMS syndrome).
• Patients with amyloidosis.
• Patients with known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \< 50% of predicted normal within 4 weeks of enrollment.
• Note: FEV1 testing is required for patients suspected of having COPD, and patients must be excluded if FEV1 \< 50% of predicted normal at any time during the study.
• Pregnant or lactating females. Because there is a potential risk for AEs in nursing infants secondary to treatment of the mother with carfilzomib in combination with iberdomide, pregnant or lactating females are excluded from study participation. These potential risks may also apply to other agents used in this study.
• Uncontrolled hypertension (ie, systolic blood pressure \[BP\] \> 160 mmHg, diastolic BP \> 100 mmHg) or diabetes

Sponsors & Collaborators

• Benjamin T Diamond, MD: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

iberdomide; carfilzomib; daratumumab; Dexamethasone; Acetaminophen; Diphenhydramine; montelukast

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Carl O Landgren, MD, PhD

  University of Miami

  PRINCIPAL INVESTIGATOR

• Benjamin Diamond, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michelle D Armogan

CONTACT

305-243-7479; mda182@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: June 9, 2023
• Study Start: February 20, 2024
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2031
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)