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Isatuximab, Bendamustine, and Prednisone for the Treatment of Refractory Multiple Myeloma

Trial Status: Active

This trial studies the side effects and best dose of bendamustine and how well it works when given together with isatuximab and prednisone for the treatment of multiple myeloma that does not respond to treatment (refractory). Immunotherapy with isatuximab, may induce changes in body’s immune system and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Anti-inflammatory drugs, such as prednisone lower the body’s immune response and are used with other drugs in the treatment of some types of cancer. Giving isatuximab, bendamustine, and prednisone may work better in treating patients with multiple myeloma compared to chemotherapy alone.

Inclusion Criteria

  • Diagnosis of multiple myeloma with a measurable disease parameter at time of screening. A measurable disease parameter is defined as one or more of the following: * Serum monoclonal protein >= 0.5 g/dL * 24 hour urine monoclonal protein >= 200 mg/24 hour * Serum free light chain ratio > 5 x normal ratio with an absolute difference of 10 mg/dL between the involved and uninvolved free light chain * Soft tissue plasmacytoma >= 2 cm measurable by either physical examination and/or applicable radiographs (e.g. magnetic resonance imaging [MRI], computed tomography [CT], etc.) * Bone marrow plasma cells >= 30%
  • Triple-class-refractory disease defined as both of the following: * Previously received treatment with a proteasome inhibitor, an immunomodulatory drug, and daratumumab in combination or as single-agents * Refractory (defined per International Myeloma Working Group [IMWG] Consensus Criteria as disease that is nonresponsive while on therapy or progresses within 60 days of last dose) to most recent therapy
  • At least 6 weeks from the last treatment with daratumumab to the first study treatment
  • Performance status of Eastern Cooperative Oncology Group (ECOG) =< 2 * Note: Participants with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible
  • Absolute neutrophil count >= 1500/mm^3
  • Platelets >= 75,000 (transfusions not permitted within 7 days of screening)
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) < 3.5 x the upper limit of the institutional normal value (ULN)
  • Total bilirubin =< 2.0 x mg/dL
  • Creatinine clearance > 30 ml/min using Cockcroft-Gault formula
  • Females of childbearing potential (FCBP) must agree to refrain from becoming pregnant while on study drug and for 3 months after discontinuation from study drug, and must agree to use adequate contraception including hormonal contraception, (e.g. birth control pills, etc.), barrier method contraception (e.g. condoms), or abstinence during that time frame. Men engaging in sexual intercourse with a FCBP must agree to use adequate contraception including hormonal contraception, (e.g. birth control pills, etc), barrier method contraception (e.g. condoms), or abstinence while on study drug and for 3 months after discontinuation from study drug
  • Ability to understand and willing to sign a written informed consent document

Exclusion Criteria

  • Prior exposure to isatuximab or bendamustine
  • History of plasma cell leukemia or multiple myeloma (MM) central nervous system (CNS) involvement
  • Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis
  • Diagnosed with another concurrent malignancy requiring treatment
  • Known active hepatitis A, B, or C
  • Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or known hypersensitivity to any of the components of study therapy
  • Receiving any other investigational agents within 14 days prior to enrollment
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry
  • Patients with human immunodeficiency virus (HIV) are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective antiretroviral therapy (ART) according to United States Department of Health and Human Services (DHHS) treatment guidelines is recommended

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE
Contact: Ravi Vij
Phone: 314-454-8304

PRIMARY OBJECTIVES:

I. To determine the maximal tolerated dose (MTD) or recommended phase 2 dose (RP2D) of isatuximab in combination with bendamustine and prednisone in participants with refractory multiple myeloma. (Phase I)

II. To evaluate the efficacy of isatuximab in combination with bendamustine and prednisone in participants with refractory multiple myeloma. (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate the safety and toxicity of isatuximab, bendamustine, and prednisone. (Both phases)

II. To evaluate progression-free survival (PFS) in participants with refractory multiple myeloma treated with isatuximab in combination with bendamustine and prednisone. (Phase II)

III. To evaluate overall survival in participants with refractory multiple myeloma treated with isatuximab in combination with bendamustine and prednisone. (Phase II)

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

Patients receive isatuximab intravenously (IV) on day 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of subsequent cycles. Patients also receive bendamustine hydrochloride IV on days 1 and 2 and prednisone IV or orally (PO) on days 1-4. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up annually for up to 5 years.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Ravi Vij

  • Primary ID 201910194
  • Secondary IDs NCI-2019-08517
  • Clinicaltrials.gov ID NCT04083898