Belantamab Mafodotin Lenalidomide and Daratumumab for the Treatment of Relapsed Refractory or Previously Untreated Multiple Myeloma

  • STATUS
    Recruiting
  • End date
    May 15, 2026
  • participants needed
    76
  • sponsor
    Mayo Clinic
Updated on 21 June 2021
cancer
hypertension
corticosteroids
dexamethasone
lenalidomide
chemotherapy regimen

Summary

This phase I/II trial studies the best dose and effect of belantamab mafodotin given together with lenalidomide and daratumumab in treating patients with multiple myeloma that has come back (relapsed), does not respond to treatment (refractory) or for which the patient has not received treatment in the past (previously untreated). Belantamab mafodotin is a monoclonal antibody, called belantamab, linked to a chemotherapy drug, called mafodotin. Belantamab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as BCMA receptors, and delivers mafodotin to kill them. Lenalidomide is an immunomodulatory drug (altering the immune effects on the tumor cell). Daratumumab is a drug that is a monoclonal antibody that is directed towards a protein on the myeloma cell. Giving belantamab mafodotin together with lenalidomide and daratumumab may kill more cancer cells.

Description

PRIMARY OBJECTIVE:

I. To determine the maximum tolerated dose (MTD) of Belantamab in combination with daratumumab and lenalidomide in patients with relapsed or refractory multiple myeloma. (Phase I) II. To assess the confirmed complete response rate following induction therapy with belantamab, daratumumab, and lenalidomide (bortezomib-dexamethasone-rituximab [BDR]), OR alternating cycles of daratumumab, lenalidomide, dexamethasone and belantamab, lenalidomide and dexamethasone, when used as initial therapy in patients with previously untreated symptomatic multiple myeloma patients. (Phase II)

SECONDARY OBJECTIVES:

I. To describe the toxicities associated with the combination of belantamab, daratumumab, and lenalidomide when used as initial therapy in patients with relapsed multiple myeloma. (Phase I) II. To assess the overall response rate (ORR) and >= very good partial response (VGPR) rate of belantamab, daratumumab, and lenalidomide (BDR) (Phase II), OR alternating cycles of daratumumab, lenalidomide, dexamethasone and belantamab, lenalidomide and dexamethasone. (Phase II) III. To assess the progression free survival and overall survival among patients with previously untreated symptomatic multiple myeloma following treatment with belantamab, daratumumab, and lenalidomide (BDR) (Phase II), OR alternating cycles of daratumumab, lenalidomide, dexamethasone and belantamab, lenalidomide and dexamethasone. (Phase II) IV. To assess the time to response (defined as the time between the date of first dose and the first documented evidence of a partial response or better) following treatment with belantamab, daratumumab, and lenalidomide (BDR) (Phase II), OR alternating cycles of daratumumab, lenalidomide, dexamethasone and belantamab, lenalidomide and dexamethasone. (Phase II) V. To describe the toxicities associated with belantamab, daratumumab, and lenalidomide (BDR) (Phase II), OR alternating cycles of daratumumab, lenalidomide, dexamethasone and belantamab, lenalidomide and dexamethasone. (Phase II)

CORRELATIVE RESEARCH OBJECTIVE:

I. Examine the rate of MRD negativity following induction therapy with the combination of belantamab, daratumumab, and lenalidomide (BDR) (Phase II), OR alternating cycles of daratumumab, lenalidomide, dexamethasone and belantamab, lenalidomide and dexamethasone. (Phase II)

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

PHASE I:

INDUCTION: Patients receive belantamab mafodotin intravenously (IV) over 30 minutes on day 1, lenalidomide orally (PO) once daily (QD) on days 1-21, and daratumumab IV over 90 minutes on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles. Treatment with belantamab mafodotin repeats every 56 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with lenalidomide and daratumumab repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Beginning cycle 13, patients receive belantamab mafodotin IV over 30 minutes on day 1 of odd number cycles, lenalidomide PO QD on days 1-21, and daratumumab IV over 90 minutes on day 1. Treatment with belantamab mafodotin repeats every 56 days, and every 28 days for lenalidomide and daratumumab in the absence of disease progression or unacceptable toxicity. Treatment with belantamab mafodotin repeats every 56 days (every other cycle) for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Treatment with lenalidomide and daratumumab repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

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

ARM A:

INDUCTION: Patients receive belantamab mafodotin IV over 30 minutes on day 1 of odd number cycles, lenalidomide PO QD on days 1-21, and daratumumab IV over 90 minutes on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Beginning cycle 13, patients receive belantamab mafodotin IV over 30 minutes on day 1 of odd number cycles (starting cycle 13), lenalidomide PO QD on days 1-21, and daratumumab IV over 90 minutes on day 1. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

ARM B:

INDUCTION: Patients receive belantamab mafodotin IV over 30 minutes on day 1 of cycles 2, 4, 6, 8, 10, and 12, lenalidomide PO QD on days 1-21, daratumumab IV over 90 minutes on days 1, 8, 15, and 22 of cycles 1 and 3, and days 1 and 15 on cycles 5, 7, 9, and 11. Patients also receive dexamethasone PO on days 1, 8, 15 and 22. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Beginning cycle 13, patients receive belantamab mafodotin IV over 30 minutes on day 1 of even numbered cycles, lenalidomide PO QD on days 1-21, and daratumumab IV over 90 minutes on day 1 of odd numbered cycles. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 3-6 months for up to 3 years.

Details
Condition Multiple Myeloma, Lymphoproliferative Disorder, Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma, Refractory Multiple Myeloma, multiple myeloma (mm)
Treatment Dexamethasone, Lenalidomide, Daratumumab, Belantamab mafodotin
Clinical Study IdentifierNCT04892264
SponsorMayo Clinic
Last Modified on21 June 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Evidence of cardiovascular disease risk, as defined by any of the following
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 =< 90 days prior to registration
Class III or IV heart failure as defined by the New York Heart Association functional classification system
Uncontrolled hypertension
History of myocardial infarction, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure) or known sensitivity to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment

Exclusion Criteria

Monoclonal gammopathy of undetermined significance or smoldering multiple myeloma
Major surgery =< 28 days prior to registration
Plasmapheresis =< 14 days prior to registration
Diagnosed or treated for another malignancy =< 2 years prior to registration or previously diagnosed with another malignancy and have any evidence of residual disease
Note: Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
Note: If there is a history of prior malignancy, they must not be receiving other specific treatment (hormone therapy, chemotherapy, or immunotherapy) for their cancer
Receiving any other concurrent chemotherapy, systemic steroids, any ancillary therapy considered investigational for treatment of multiple myeloma, or receiving radiotherapy =< 14 days or five half-lives, whichever is shorter, prior to first dose of study treatment. Note: Bisphosphonates are considered to be supportive care rather than therapy and are thus allowed while on protocol treatment
Known to be human immunodeficiency virus (HIV) positive
Presence of positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment
Note: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained
Note: Hepatitis RNA testing is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing
Uncontrolled intercurrent illness including, but not limited to
Ongoing or active infection (defined as infection undergoing treatment)
Active mucosal or internal bleeding
Social situations that would limit compliance with study requirements
Corneal epithelial disease (except for mild changes in the corneal epithelium)
Known gastrointestinal disease (including difficulty swallowing) or gastrointestinal procedure that could interfere with the oral absorption or tolerance of lenalidomide or dexamethasone
Unstable liver or biliary 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) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria
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