Belantamab Mafodotin, Cyclophosphamide, and Dexamethasone in Relapsed/Refractory Multiple Myeloma

NCT04896658 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 2060GCCC
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluate the efficacy and safety of Belantamab Mafodotin, cyclophosphamide, and dexamethasone in patients with Relapsed/Refractory Multiple Myeloma

Conditions

Relapsed/Refractory Multiple Myeloma

Keywords

Belantamab mafodotin; Relapsed/Refractory Multiple Myeloma; Maximum tolerated doses; Overall response rate; Overall survival; Dose limiting toxicities

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events in Dose Escalation

  Overall incidence and severity of Adverse Events in Number of Participants with Adverse Events in Dose Escalation

  Up to 6 weeks

• Response Rate in Dose Escalation and Expansion Cohort

  Number of Participants With response rate in Dose Escalation and Expansion Cohort. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  Up to 12 weeks

Secondary Outcomes (3)

• Number of Participants With Disease Progression

  From date of randomization until the date of death from any cause, assessed up to 3 years

• Number of Participants According to Best Response

  From date of randomization until the date of death from any cause, assessed up to 3 years

• Overall Survival

  From date of randomization until the date of death from any cause, assessed up to 3 years

Other Outcomes (1)

• Cytokine Profile Data

  From date of randomization until the date of death from any cause, assessed up to 3 years

Study Arms (2)

Arm A

EXPERIMENTAL

1. Dose level 1: The subject will take 1.9 mg/kg of Belantamab Mafodotin, 300 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 of each 3 weeks cycles. 2. Dose level 2: The subject will take 1.9 mg/kg of Belantamab Mafodotin, 500 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 each 3 weeks cycles.

Drug: Belantamab Mafodotin, Cyclophosphamide and Dexamethasone

Arm B

EXPERIMENTAL

1. Dose level 1: The subject will take 2.5 mg/kg of Belantamab Mafodotin, 300 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 of each 6 weeks cycles. 2. Dose level 2: The subject will take 2.5 mg/kg of Belantamab Mafodotin, 500 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 each 6 weeks cycles.

Drug: Belantamab Mafodotin, Cyclophosphamide and Dexamethasone

Interventions

Belantamab Mafodotin, Cyclophosphamide and Dexamethasone DRUG

Study drug

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of Refractory MM; failed at least 3 prior lines of anti-myeloma treatments, including an anti-CD38 antibody (e.g., daratumumab) alone or in combination, and is refractory to an IMiD (i.e., lenalidomide or pomalidomide), and to a proteasome inhibitor (e.g., bortezomib, ixazomib or carfilzomib). (Refractory myeloma is defined as disease that is nonresponsive while on primary or salvage therapy or progresses within 60 days of last therapy. Nonresponsive disease is defined as either failure to achieve at least minimal response or development of progressive disease (PD) while on therapy).
• Has measurable disease with at least one of the following:
• Serum M-protein ≥0.5 g/dL (≥ 5 g/L)
• Urine M-protein ≥ 200 mg/24h
• Serum FLC assay: Involved FLC level ≥10 mg/dL and an abnormal ratio (\<0.26 or \>1.65)
• Provide signed written informed consent.
• years or older (at the time consent is obtained).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Participants with a history of autologous stem cell transplant or Prior BCMA targeted therapy (e.g. CAR-T cells, BiTes) can enroll on the study provided that:
• Therapy was \>100 days prior to study enrolment.
• No active infection(s).
• Female and Male patients: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Prior treatment-related toxicities must be ≤ Grade 1 except peripheral neuropathy (Grade-2).

You may not qualify if:

• Systemic anti-myeloma therapy within ≤14 days or 5 half-lives, whichever is shorter, or plasmapheresis within 7 days prior to treatment.
• Systemic treatment with high dose steroids (equivalent to ≥ 60 mg prednisone daily for ≥4 days) within the past 14 days.
• Symptomatic amyloidosis, active CNS disease, active plasma cell leukemia at the time of screening.
• Prior allogeneic stem cell transplant (SCT). NOTE - Participants who have undergone syngeneic transplant may be allowed if no history of GvHD.
• Current corneal epithelial disease except mild punctate keratopathy.
• Evidence of active bleeding.
• Any major surgery within the last four weeks.
• Any serious and/or unstable pre-existing medical, psychiatric disorder or lab abnormalities that affect patients' safety, obtaining informed consent or compliance with study procedures.
• Current unstable liver disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria.
• Other malignancies except for malignancy from which the patients have been disease-free \> 2 years.
• Evidence of cardiovascular disease including any of the following:
• Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities including second degree (Mobitz Type II) or third degree atrioventricular (AV) block.
• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening.
• Class III or IV heart failure as defined by the New York Heart Association functional classification system.
• Uncontrolled hypertension.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland

Baltimore, Maryland, 21201, United States

Location

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MeSH Terms

Conditions

Multiple Myeloma

Interventions

belantamab mafodotin; Cyclophosphamide; Dexamethasone

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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Ashraf Badros, MD
• Organization: University of Maryland, Baltimore

abadros@umm.edu

410-328-1230

Study Officials

• Ashraf Badros, MB; ChB

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Multiple Myeloma Service

Model Details: Phase I 1. Arm A (cycles repeated every 3 weeks) 1. Dose level 1: The subject will take 1.9 mg/kg of Belantamab Mafodotin, 300 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 of each 3 weeks cycles. 2. Dose level 2: The subject will take 1.9 mg/kg of Belantamab Mafodotin, 500 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 of each 3 weeks cycles. 2. Arm B (cycles repeated every 6 weeks) 1. Dose level 1: The subject will take 2.5 mg/kg of Belantamab Mafodotin, 300 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 of each 6 weeks cycles. 2. Dose level 2: The subject will take 2.5 mg/kg of Belantamab Mafodotin, 500 mg of Cyclophosphamide, and 40 mg of Dexamethasone on day 1 of each 6 weeks cycles. Phase II : Phase II was stopped with the FDA withdrawal of the drug approval and reluctance of patients to participate.

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: May 21, 2021
• Study Start: December 3, 2021
• Primary Completion: June 30, 2023
• Study Completion: December 1, 2024
• Last Updated: April 3, 2025
• Results First Posted: April 3, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)