Refractory Multiple Myeloma Clinical Trial
Official title:
A Phase 1 Dose-Escalation and Exploratory Dose Expansion Study of KRT-232 (AMG 232) in Combination With Carfilzomib, Lenalidomide, and Dexamethasone in Relapsed and/or Refractory Myeloma
This phase I trial studies the side effects and best dose of MDM2 Inhibitor KRT-232 when given together with carfilzomib, lenalidomide, and dexamethasone in treating patient with multiple myeloma that has come back (relapsed) or has not responded to previous treatment (refractory). KRT-232 (AMG 232) may stop the growth of cancer cells by blocking a protein called MDM2 that is needed for cell growth. Lenalidomide help shrink or slow the growth of multiple myeloma. Drugs used in chemotherapy, such as carfilzomib 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. Giving MDM2 Inhibitor KRT-232, lenalidomide, carfilzomib, and dexamethasone together may work better in treating patients with multiple myeloma.
PRIMARY OBJECTIVES: I. Evaluate safety and tolerability of MDM2 Inhibitor KRT-232 (KRT-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 KRT-232 (AMG 232) in combination with carfilzomib, lenalidomide, and dexamethasone (KRd). (Part A) III. Confirm the safety and tolerability of KRT-232 (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 KRT-232 (AMG 232) through serum MIC-1 levels. (Part A) II. Assess KRT-232 (AMG 232) exposure-response relationships (PD, toxicity, and efficacy). (Part A) III. Evaluate the overall response rate of KRT-232 (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 KRT-232 (AMG 232) through serum MIC-1 levels. (Part B) V. Assess KRT-232 (AMG 232) exposure-response relationships (PD, toxicity, and efficacy). (Part B) EXPLORATORY OBJECTIVES: I. To observe and record anti-tumor activity of KRT-232 (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. (Parts A and B) OUTLINE: This is a dose-escalation study of MDM2 Inhibitor KRT-232. Patients receive MDM2 Inhibitor KRT-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 cycles 1-12 and on days 1-2 and 15-16 of cycles 13-18, lenalidomide PO on days 1-21, and dexamethasone PO or dexamethasone sodium phosphate IV on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unexpected toxicity. Patients undergo echocardiography during screening and bone marrow biopsy and aspiration, and blood sample collection throughout the study. After completion of study treatment, patients are followed up for 30 days. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Active, not recruiting |
NCT04083534 -
First In Human (FIH) Study of REGN5459 in Adult Patients With Relapsed or Refractory Multiple Myeloma (MM)
|
Phase 1/Phase 2 | |
| Completed |
NCT01775553 -
Study of High Dose Carfilzomib in Multiple Myeloma Patients Who Have Progressed On Standard Dose Carfilzomib
|
Phase 2 | |
| Terminated |
NCT02020941 -
Carfilzomib in Treating Patients With Multiple Myeloma in First Relapse or Refractory to First-Line Therapy
|
Phase 2 | |
| Completed |
NCT01212952 -
Pomalidomide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 1/Phase 2 | |
| Completed |
NCT01233921 -
Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer
|
N/A | |
| Terminated |
NCT01078441 -
Bortezomib, Liposomal Doxorubicin Hydrochloride, Dexamethasone, and Cyclophosphamide in Treating Patients With Multiple Myeloma That Relapsed After Autologous Stem Cell Transplant
|
Phase 2 | |
| Completed |
NCT00514137 -
Sunitinib in Treating Patients With Relapsed Multiple Myeloma
|
Phase 2 | |
| Completed |
NCT00306813 -
Evaluation of Lenalidomide, Doxorubicin and Dexamethasone (RAD) in Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 1/Phase 2 | |
| Completed |
NCT00078858 -
Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant
|
Phase 1/Phase 2 | |
| Completed |
NCT00047203 -
Flavopiridol in Treating Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 2 | |
| Active, not recruiting |
NCT03731832 -
Pomalidomide, Ixazomib, and Dexamethasone With or Without Intensification by Cyclophosphamide in Relapsed or Refractory Multiple Myeloma
|
Phase 2 | |
| Completed |
NCT00003196 -
Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma
|
N/A | |
| Recruiting |
NCT03601624 -
Pomalidomide/Cyclophosphamide/Dexamethasone in Relapse Refractory Myeloma: Safety Profile in Mexicans
|
Phase 2 | |
| Terminated |
NCT01954784 -
Lenalidomide After Donor Stem Cell Transplant and Bortezomib in Treating Patients With High Risk Multiple Myeloma
|
Phase 1 | |
| Recruiting |
NCT05020444 -
TriPRIL CAR T Cells in Multiple Myeloma
|
Phase 1 | |
| Completed |
NCT01588015 -
Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant
|
Phase 1 | |
| Recruiting |
NCT04302324 -
A Phase II Study of Daratumumab, Clarithromycin, Pomalidomide And Dexamethasone (D-ClaPd) In Multiple Myeloma Patients Previously Exposed to Daratumumab
|
Phase 2 | |
| Recruiting |
NCT06119685 -
IDP-023 as a Single Agent and in Combination With Antibody Therapies in Patients With Advanced Hematologic Cancers
|
Phase 1/Phase 2 | |
| Completed |
NCT00118170 -
Sorafenib in Treating Patients With Metastatic or Unresectable Solid Tumors, Multiple Myeloma, or Non-Hodgkin's Lymphoma With or Without Impaired Liver or Kidney Function
|
Phase 1 | |
| Completed |
NCT00054353 -
Reduced-Intensity Conditioning Followed By Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Multiple Myeloma
|
Phase 1/Phase 2 |