Testing the Combination of Two Approved Drugs and One Experimental Drug in Patients With Relapsed or Refractory Multiple Myeloma

NCT06232044 | Recruiting Phase 1

• 2 other identifiers: A062101NCI-2023-09710
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 40

Brief Summary

This phase I/II trial tests the safety, side effects, best dose, and effectiveness of iberdomide in combination with belantamab mafodotin and dexamethasone in treating patients with multiple myeloma (MM) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Multiple myeloma is a cancer that affects white blood cells called plasma cells, which are made in the bone marrow and are part of the immune system. Multiple myeloma cells have a protein on their surface called B-cell maturation antigen (BCMA) that allows the cancer cells to survive and grow. Immunotherapy with iberdomide, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Belantamab mafodotin has been designed to attach to the BCMA protein, which may cause the myeloma cell to become damaged and die. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Iberdomide plus belantamab mafodotin may help slow or stop the growth of cancer in patients with multiple myeloma.

Conditions

Refractory Multiple Myeloma; Recurrent Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of iberdomide (Phase I)

  MTD will be defined as the highest dose level among those tested where at most one out of 6 patients develops a DLT prior to the start of their second cycle of treatment. Will be assessed by NCI CTCAE v 5.0.

  During the first cycle of therapy, up to 28 days

• Progression-free survival (PFS) (Phase II)

  Will be compared between the two treatment arms. the methods of Kaplan and Meier will be used to graphically evaluate these distributions as well as to estimate the median PFS and corresponding 95% confidence intervals.

  From randomization to the time of documented disease progression and/or death due to any cause, assessed up to 3 years

Secondary Outcomes (5)

• Rate of grade 3+ Adverse Events (AEs)

  Up to 3 years

• Complete response (CR) rate

  up to 3 years

• Overall response rate (ORR)

  up to 3 years

• Duration of response (DoR)

  p to 3 years

• Overall Survival (OS)

  Up to 3 years.

Study Arms (3)

Phase I (iberdomide, belantamab mafodotin, dexamethasone)

EXPERIMENTAL

Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.

Drug: Iberdomide; Biological: Belantamab Mafodotin; Drug: Dexamethasone; Procedure: Echocardiography; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspiration; Procedure: Biospecimen Collection

Phase II, Arm I (belantamab mafodotin, dexamethasone)

ACTIVE COMPARATOR

Patients receive belantamab mafodotin IV on day 1 and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients who progress may cross over to Arm II. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo a bone marrow biopsy and aspiration and blood sample collection throughout trial.

Biological: Belantamab Mafodotin; Drug: Dexamethasone; Procedure: Echocardiography; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspiration; Procedure: Biospecimen Collection

Phase II, Arm II (iberdomide, belantamab mafodotin)

EXPERIMENTAL

Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin IV on day 1, and dexamethasone PO on days 1, 8, 15, 22, 29, 36, 43, and 50 of each cycle. Cycles repeat every 56 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening as clinically indicated and CT, MRI and/or PET scans during screening and as clinically indicated on study. Patients also undergo bone marrow biopsy and aspiration and blood sample collection throughout trial.

Drug: Iberdomide; Biological: Belantamab Mafodotin; Drug: Dexamethasone; Procedure: Echocardiography; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspiration; Procedure: Biospecimen Collection

Interventions

Belantamab Mafodotin BIOLOGICAL

Receive IV

Phase I (iberdomide, belantamab mafodotin, dexamethasone); Phase II, Arm I (belantamab mafodotin, dexamethasone); Phase II, Arm II (iberdomide, belantamab mafodotin)

Dexamethasone DRUG

Receive PO

Phase I (iberdomide, belantamab mafodotin, dexamethasone); Phase II, Arm I (belantamab mafodotin, dexamethasone); Phase II, Arm II (iberdomide, belantamab mafodotin)

Echocardiography PROCEDURE

Undergo ECHO

Phase I (iberdomide, belantamab mafodotin, dexamethasone); Phase II, Arm I (belantamab mafodotin, dexamethasone); Phase II, Arm II (iberdomide, belantamab mafodotin)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CT Scan, CAT Scan

Phase I (iberdomide, belantamab mafodotin, dexamethasone); Phase II, Arm I (belantamab mafodotin, dexamethasone); Phase II, Arm II (iberdomide, belantamab mafodotin)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: PET Scan

Phase I (iberdomide, belantamab mafodotin, dexamethasone); Phase II, Arm I (belantamab mafodotin, dexamethasone); Phase II, Arm II (iberdomide, belantamab mafodotin)

Bone Marrow Biopsy PROCEDURE

Undergo Bone Marrow Biopsy

Phase I (iberdomide, belantamab mafodotin, dexamethasone); Phase II, Arm I (belantamab mafodotin, dexamethasone); Phase II, Arm II (iberdomide, belantamab mafodotin)

Bone Marrow Aspiration PROCEDURE

Undergo Bone Marrow Aspirate

Phase I (iberdomide, belantamab mafodotin, dexamethasone); Phase II, Arm I (belantamab mafodotin, dexamethasone); Phase II, Arm II (iberdomide, belantamab mafodotin)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Phase I (iberdomide, belantamab mafodotin, dexamethasone); Phase II, Arm I (belantamab mafodotin, dexamethasone); Phase II, Arm II (iberdomide, belantamab mafodotin)

Iberdomide DRUG

Receive PO

Phase I (iberdomide, belantamab mafodotin, dexamethasone); Phase II, Arm II (iberdomide, belantamab mafodotin)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: MRI

Phase I (iberdomide, belantamab mafodotin, dexamethasone); Phase II, Arm I (belantamab mafodotin, dexamethasone); Phase II, Arm II (iberdomide, belantamab mafodotin)

Eligibility Criteria

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

You may qualify if:

• No evidence of active mucosal or internal bleeding.
• No known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to belamaf or drugs chemically related to belamaf, or any of the components of the study treatment.
• Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening.
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study. Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment. Participant must not have current corneal epithelial disease except mild changes in corneal epithelium. For belantamab mafodotin, concomitant administration with strong inhibitors of OATP should be avoided.
• RE-REGISTRATION ELIGIBILITY CRITERIA: Patients must meet criteria for progression of myeloma as defined by IMWG criteria indicated as any of the following:
• ≥ 25% increase in M-protein (must be at least 0.5 g/dl above nadir from last treatment regimen).
• % difference between involved and uninvolved serum free light chains from its nadir or
• The development of new plasmacytomas or hypercalcemia not due to other causes. In the absence of progression by serum M protein or free light chain, biopsy of new plasmacytoma of extramedullary disease is warranted.
• If refractory myeloma, it should be defined by IMWG criteria as disease which has become non-responsive or progressive on belamaf/dexamethasone.
• RE-REGISTRATION ELIGIBILITY CRITERIA: Measurable disease defined by IMWG criteria as:
• Serum M-protein ≥ 0.5 g/dL.
• Urine monoclonal protein ≥ 200 mg/24h.
• Serum FLC assay: Involved FLC level ≥ 10 mg/dl (≥ 100 mg/l) and serum free light chain ratio is abnormal.
• PET/CT or MRI findings consistent with (c/w) disease progression.
• RE-REGISTRATION ELIGIBILITY CRITERIA: Absolute neutrophil count (ANC) ≥ 1,000/mm\^3.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Alliance for Clinical Trials in Oncology: lead

Study Sites (40)

Mary Greeley Medical Center

Ames, Iowa, 50010, United States

RECRUITING

McFarland Clinic - Ames

Ames, Iowa, 50010, United States

RECRUITING

McFarland Clinic - Boone

Boone, Iowa, 50036, United States

SUSPENDED

McFarland Clinic - Trinity Cancer Center

Fort Dodge, Iowa, 50501, United States

RECRUITING

McFarland Clinic - Jefferson

Jefferson, Iowa, 50129, United States

SUSPENDED

McFarland Clinic - Marshalltown

Marshalltown, Iowa, 50158, United States

RECRUITING

Tufts Medical Center

Boston, Massachusetts, 02111, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota, 56303, United States

RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

OhioHealth O'Bleness Hospital

Athens, Ohio, 45701, United States

RECRUITING

Columbus Oncology and Hematology Associates Inc

Columbus, Ohio, 43214, United States

RECRUITING

Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

RECRUITING

Grant Medical Center

Columbus, Ohio, 43215, United States

RECRUITING

Doctors Hospital

Columbus, Ohio, 43228, United States

RECRUITING

Delaware Health Center-Grady Cancer Center

Delaware, Ohio, 43015, United States

RECRUITING

Grady Memorial Hospital

Delaware, Ohio, 43015, United States

RECRUITING

Columbus Oncology and Hematology Associates

Dublin, Ohio, 43016, United States

RECRUITING

Dublin Methodist Hospital

Dublin, Ohio, 43016, United States

RECRUITING

OhioHealth Mansfield Hospital

Mansfield, Ohio, 44903, United States

RECRUITING

OhioHealth Marion General Hospital

Marion, Ohio, 43302, United States

RECRUITING

OhioHealth Pickerington Methodist Hospital

Pickerington, Ohio, 43147, United States

RECRUITING

OhioHealth Westerville Medical Campus/Westerville Cancer Center

Westerville, Ohio, 43082, United States

RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States

RECRUITING

Saint Vincent Hospital Cancer Center at Saint Mary's

Green Bay, Wisconsin, 54303, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

ProHealth D N Greenwald Center

Mukwonago, Wisconsin, 53149, United States

RECRUITING

ProHealth Oconomowoc Memorial Hospital

Oconomowoc, Wisconsin, 53066, United States

RECRUITING

Saint Vincent Hospital Cancer Center at Sheboygan

Sheboygan, Wisconsin, 53081, United States

RECRUITING

Sheboygan Physicians Group

Sheboygan, Wisconsin, 53081, United States

RECRUITING

Saint Vincent Hospital Cancer Center at Sturgeon Bay

Sturgeon Bay, Wisconsin, 54235-1495, United States

RECRUITING

ProHealth Waukesha Memorial Hospital

Waukesha, Wisconsin, 53188, United States

RECRUITING

UW Cancer Center at ProHealth Care

Waukesha, Wisconsin, 53188, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

iberdomide; belantamab mafodotin; Dexamethasone; Magnetic Resonance Spectroscopy

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; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Central Study Contacts

Monique Hartley-Brown, MD

CONTACT

857-215-1692; MoniqueA_Hartley-Brown@dfci.harvard.edu

Destin Carlisle

CONTACT

773-702-8824; dcarlisle@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2024
• First Posted: January 30, 2024
• Study Start: April 23, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): August 1, 2030
• Last Updated: March 25, 2026

Record last verified: 2026-03

Locations

US (40)