Last updated on June 2019

MDM2 Inhibitor AMG-232 Carfilzomib Lenalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma


Brief description of study

This phase I trial studies the side effects and best dose of MDM2 inhibitor AMG-232 when given together with carfilzomib, lenalidomide, and dexamethasone in treating patient with multiple myeloma that has come back of has not responded to previous treatment. Drugs used in chemotherapy, such as MDM2 inhibitor AMG-232, carfilzomib, lenalidomide, and dexamethasone, 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.

Detailed Study Description

PRIMARY OBJECTIVES:

I. Evaluate safety and tolerability of MDM2 inhibitor AMG-232 (AMG-232) in combination with carfilzomib, lenalidomide, and dexamethasone (KRd). (Part A) II. Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMG-232 in combination with carfilzomib, lenalidomide, and dexamethasone (KRd). (Part A) III. Confirm the safety and tolerability of AMG 232 in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) at MTD/tentative RP2D in a goal of 10 subjects with relapsed and/or refractory myeloma. (Part B)

SECONDARY OBJECTIVES:

I. Evaluate progressive disease (PD) effects of AMG-232 through serum MIC-1 levels. (Part A) II. Assess AMG-232 exposure-response relationships (PD, toxicity, and efficacy). (Part A) III. Evaluate the overall response rate of AMG 232 in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in relapsed/refractory myeloma by International Myeloma Working Group (IMWG) criteria. (Part B) IV. Evaluate PD effects of AMG 232 through serum MIC-1 levels. (Part B) V. Assess AMG 232 exposure-response relationships (PD, toxicity, and efficacy). (Part B)

EXPLORATORY OBJECTIVES:

I. To observe and record anti-tumor activity of AMG-232 in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in relapsed/refractory myeloma by International Myeloma Working Group (IMWG) criteria. (Part A) II. Evaluate ribonucleic acid (RNA) expression levels of relevant genes in the TP53 pathway that may predict response to therapy using pre- and post-treatment bone marrow biopsies. (Part A) III. Evaluate ribonucleic acid (RNA) expression levels of relevant genes in the TP53 pathway that may predict response to therapy using preand post-treatment bone marrow biopsies. (Part B)

OUTLINE: This is a dose-escalation study of MDM2 inhibitor AMG-232.

Patients receive MDM2 inhibitor AMG-232 orally (PO) once daily (QD) on days 1-7, carfilzomib intravenously (IV) over 10-30 minutes on days 1-2, 8-9, and 15-16 of courses 1-12 and on days 1-2 and 15-16 of courses 13-18, lenalidomide PO on days 1-21, and dexamethasone PO or IV on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unexpected toxicity.

After completion of study treatment, patients are followed up for 30 days.

Clinical Study Identifier: NCT03031730

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Recruitment Status: Open


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