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

NCT ID: NCT06232044

Last Updated: 2026-02-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

88 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-23

Study Completion Date

2030-08-01

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine maximum tolerated dose (MTD) of iberdomide (CC-220) in combination with belantamab mafodotin and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM). (PHASE I) II. To determine whether the combination of belantamab mafodotin/ iberdomide/dexamethasone improves progression-free survival (PFS) relative to belantamab mafodotin/dexamethasone in patients with RRMM. (PHASE II)

SECONDARY OBJECTIVES:

I. To summarize the incidence and cause for treatment delays, modifications and omissions. (PHASE I) II. To assess treatment response. (PHASE I) III. To obtain an estimate of the progression-free survival (PFS) and overall survival (OS) distribution. (PHASE I) IV. To determine minimal residual disease (MRD) negativity. (PHASE I) V. To observe and record anti-tumor activity. (PHASE I) VI. To determine whether the combination of belantamab mafodotin/ iberdomide/dexamethasone improves overall survival (OS) compared to belantamab mafadotin/dexamethasone in patients with RRMM. (PHASE II) VII. To evaluate the safety profile. (PHASE II) VIII. To estimate the ORR (per International Myeloma Working Group \[IMWG\] criteria), duration of response (DoR), and time to relapse (TTR). (PHASE II) XI. To determine MRD status. (PHASE II)

EXPLORATORY OBJECTIVES:

I. To examine changes in T, NK, and B-cell subsets and quantitative immunoglobulin levels after 1, 3, 6 and 12 cycles of treatment.

II. To investigate whether BCMA protein expression on MM cells at diagnosis as well as at relapse or end of study (including loss of expression) is associated with outcome (OS and PFS).

OUTLINE: This is a phase I, dose-escalation study of iberdomide followed by a phase II study.

PHASE I: Patients receive iberdomide orally on days 1-21 and 29-49, belantamab mafodotin intravenously (IV) on day 1, and dexamethasone orally (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 echocardiography (ECHO) during screening as clinically indicated and computed tomography (CT), magnetic resonance imaging (MRI) and/or positron emission tomography (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.

PHASE II: Patients are randomized to 1 of 2 arms.

ARM I: 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.

ARM II: 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.

After completion of study treatment, patients are followed up every 6 months for 3 years from study entry.

Conditions

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Recurrent Multiple Myeloma Refractory Multiple Myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase I (iberdomide, belantamab mafodotin, dexamethasone)

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.

Group Type EXPERIMENTAL

Iberdomide

Intervention Type DRUG

Receive PO

Belantamab Mafodotin

Intervention Type BIOLOGICAL

Receive IV

Dexamethasone

Intervention Type DRUG

Receive PO

Echocardiography

Intervention Type PROCEDURE

Undergo ECHO

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo Bone Marrow Biopsy

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo Bone Marrow Aspirate

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Phase II, Arm I (belantamab mafodotin, dexamethasone)

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.

Group Type ACTIVE_COMPARATOR

Belantamab Mafodotin

Intervention Type BIOLOGICAL

Receive IV

Dexamethasone

Intervention Type DRUG

Receive PO

Echocardiography

Intervention Type PROCEDURE

Undergo ECHO

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo Bone Marrow Biopsy

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo Bone Marrow Aspirate

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Phase II, Arm II (iberdomide, belantamab mafodotin)

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.

Group Type EXPERIMENTAL

Iberdomide

Intervention Type DRUG

Receive PO

Belantamab Mafodotin

Intervention Type BIOLOGICAL

Receive IV

Dexamethasone

Intervention Type DRUG

Receive PO

Echocardiography

Intervention Type PROCEDURE

Undergo ECHO

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo Bone Marrow Biopsy

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo Bone Marrow Aspirate

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Interventions

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Iberdomide

Receive PO

Intervention Type DRUG

Belantamab Mafodotin

Receive IV

Intervention Type BIOLOGICAL

Dexamethasone

Receive PO

Intervention Type DRUG

Echocardiography

Undergo ECHO

Intervention Type PROCEDURE

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PET

Intervention Type PROCEDURE

Bone Marrow Biopsy

Undergo Bone Marrow Biopsy

Intervention Type PROCEDURE

Bone Marrow Aspiration

Undergo Bone Marrow Aspirate

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Other Intervention Names

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CT Scan CAT Scan MRI PET Scan

Eligibility Criteria

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Inclusion Criteria

* ≥ 45 years of age and has not had menses for \> 1 year
* Patients who have been amenorrhoeic for \< 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
* Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.
* Male patients must agree to use an adequate method of contraception for the duration of the study and for 6 months afterwards.
* Male participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies: Male participants are eligible to participate if they agree to the following during the intervention period and for 6 months after the last dose of study treatment to allow for clearance of any altered sperm:
* Refrain from donating sperm PLUS, either:
* Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR
* Must agree to use contraception/barrier as detailed below:
* Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of \< 1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females).
* Archival tissue must be available for submission for the mandatory correlative studies.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

\* Patients with treated brain metastases are eligible if follow up brain imaging after central nervous system (CNS) directed therapy shows no evidence of progression.
* No patients with uncontrolled human immunodeficiency virus (HIV), hepatitis C and B. Testing for HIV and hepatitis C and B are not required prior to registration.

\* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* No positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to registration unless the participant can meet the following criteria:

* RNA test negative.
* Successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative hepatitis C virus (HCV) RNA test after a washout period of at least 4 weeks.
* Patients with hepatitis B will be excluded unless the following criteria can be met.

* Serology: Hepatitis B core antibody positive (HbcAb)+, hepatitis B surface antigen (HbsAg)-.
* Screening: Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) undetectable.
* During study treatment: Monitoring per protocol.
* During study treatment: Antiviral treatment instituted if HBV DNA becomes detectable.
* Serology: HBsAg+ at screen or within 3 months prior to registration.
* Screening: HBV DNA undetectable.
* Screening: Highly effective antiviral treatment started at least 4 weeks prior to first registration.
* Screening: Baseline imaging per protocol.
* Screening: Participants with cirrhosis are excluded.
* During study treatment: Antiviral treatment maintained throughout study treatment.
* During study treatment: Monitoring and management per protocol. \*\* Note: Presence of isolated hepatitis (Hep) B surface antibody (HBsAb) indicating previous vaccination will not exclude a participant.
* No patients with unacceptable cardiac risk factors defined by any of the following criteria:

* Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block.
* History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within three (3) months of Screening.
* Class III or IV heart failure as defined by the New York Heart Association functional classification system \[Error! Reference source not found., 1994\].
* Uncontrolled hypertension.
* Patients with congenital long QT syndrome, QTcF interval QTcF \> 480 msec (the QT interval values must be corrected for heart rate by Fridericia's formula \[QTcF\]).
* Any history of ventricular fibrillation or torsade de pointes.
* Symptomatic bradycardia defined as heart rate (HR) \< 50 bpm with associated dizziness/syncope.
* Left ventricular ejection fraction \< 30%.
* No patients who have received targeted (non-monoclonal antibodies \[mAb\]) or investigational agents within 2 weeks prior to rgistration and who have not recovered from side effects of those therapies.
* No patients who have undergone major surgery ≤ 2 weeks prior to registration or who have not recovered from the side-effects of surgery.
* No known medical condition causing an inability to swallow oral formulations of agents.
* No active bacterial, viral or fungal infection (s) present.
* Patients cannot have a Child-Pugh score greater than 1 (absent ascites, total bilirubin \< 2, international normalized ratio (INR) \<1.7 (unless on anticoagulation), and no encephalopathy; esophageal or gastric varices, and cirrhosis. Note: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria.
* 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).
* 25% 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.
* RE-REGISTRATION ELIGIBILITY CRITERIA: Platelet Count ≥ 75,000/mm\^3 (or ≥ 50,000/mm\^3 if BM plasma cells \> 50%).
* RE-REGISTRATION ELIGIBILITY CRITERIA: Calc. creatinine clearance ≥ 30 mL/min using Cockcroft-Gault equation.
* RE-REGISTRATION ELIGIBILITY CRITERIA: Total bilirubin ≤ 2 mg/dL.
* RE-REGISTRATION ELIGIBILITY CRITERIA: AST/ALT ≤ 2.5 x upper limit of normal (ULN).
* RE-REGISTRATION ELIGIBILITY CRITERIA: Alkaline phosphatase ≤ 3 x ULN.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Mary Greeley Medical Center

Ames, Iowa, United States

Site Status

McFarland Clinic - Ames

Ames, Iowa, United States

Site Status

McFarland Clinic - Boone

Boone, Iowa, United States

Site Status

McFarland Clinic - Trinity Cancer Center

Fort Dodge, Iowa, United States

Site Status

McFarland Clinic - Jefferson

Jefferson, Iowa, United States

Site Status

McFarland Clinic - Marshalltown

Marshalltown, Iowa, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota, United States

Site Status

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Site Status

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Site Status

Memorial Sloan Kettering Commack

Commack, New York, United States

Site Status

Memorial Sloan Kettering Westchester

Harrison, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

OhioHealth O'Bleness Hospital

Athens, Ohio, United States

Site Status

Columbus Oncology and Hematology Associates Inc

Columbus, Ohio, United States

Site Status

Riverside Methodist Hospital

Columbus, Ohio, United States

Site Status

Grant Medical Center

Columbus, Ohio, United States

Site Status

Doctors Hospital

Columbus, Ohio, United States

Site Status

Delaware Health Center-Grady Cancer Center

Delaware, Ohio, United States

Site Status

Grady Memorial Hospital

Delaware, Ohio, United States

Site Status

Columbus Oncology and Hematology Associates

Dublin, Ohio, United States

Site Status

Dublin Methodist Hospital

Dublin, Ohio, United States

Site Status

OhioHealth Mansfield Hospital

Mansfield, Ohio, United States

Site Status

OhioHealth Marion General Hospital

Marion, Ohio, United States

Site Status

OhioHealth Pickerington Methodist Hospital

Pickerington, Ohio, United States

Site Status

OhioHealth Westerville Medical Campus/Westerville Cancer Center

Westerville, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, United States

Site Status

Saint Vincent Hospital Cancer Center at Saint Mary's

Green Bay, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

ProHealth D N Greenwald Center

Mukwonago, Wisconsin, United States

Site Status

ProHealth Oconomowoc Memorial Hospital

Oconomowoc, Wisconsin, United States

Site Status

Saint Vincent Hospital Cancer Center at Sheboygan

Sheboygan, Wisconsin, United States

Site Status

Sheboygan Physicians Group

Sheboygan, Wisconsin, United States

Site Status

Saint Vincent Hospital Cancer Center at Sturgeon Bay

Sturgeon Bay, Wisconsin, United States

Site Status

ProHealth Waukesha Memorial Hospital

Waukesha, Wisconsin, United States

Site Status

UW Cancer Center at ProHealth Care

Waukesha, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2023-09710

Identifier Type: OTHER

Identifier Source: secondary_id

A062101

Identifier Type: -

Identifier Source: org_study_id

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