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

Refractory Multiple Myeloma Clinical Trial

Official title: A Phase I/II Study of the Safety, Tolerability and Efficacy of Belantamab Mafodotin (GSK2857916) in Combination With Iberdomide (CC-220)/Dexamethasone Versus Belantamab Mafodotin (GSK2857916)/Dexamethasone in Relapsed Refractory Multiple Myeloma

Status Not yet recruiting

Clinical Trial 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.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Recurrent Multiple Myeloma
• Refractory Multiple Myeloma

• NCT number: NCT06232044
• Study type: Interventional
• Source: Alliance for Clinical Trials in Oncology
• Contact: Monique Hartley-Brown, MD
• Phone: 857-215-1692
• Email: MoniqueA_Hartley-Brown@dfci.harvard.edu
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: August 30, 2024
• Completion date: August 1, 2030