Clinical Trials Logo

Clinical Trial Summary

This randomized phase II trial studies how well ixazomib and dexamethasone or ixazomib, dexamethasone, and lenalidomide work based on the presence of the rearrangement of a gene called nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (NFKB2) in treating patients with multiple myeloma that has returned after a period of improvement or does not respond to treatment. Ixazomib may stop the growth of cancer cells by blocking enzymes called proteasomes needed for cell growth. Drugs used in chemotherapy, such as 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. Lenalidomide may stimulate the immune system against cancer cells and may also prevent the growth of new blood vessels that tumors need to grow. It is not yet known whether ixazomib and dexamethasone, or ixazomib, dexamethasone, and lenalidomide are more effective in treating multiple myeloma.


Clinical Trial Description

PRIMARY OBJECTIVES: To test whether the NFKB2 rearrangement can guide the selection of treatment (ixazomib [ixazomib citrate] plus dexamethasone [Id] or ixazomib plus lenalidomide and dexamethasone [IRd]) by conducting the following comparisons: I. To compare the response rate at 4 cycles between patients treated with Id and patients treated with IRd and confirm the lack of significant difference in overall response. II. To compare the response rate at 4 cycles between non-rearranged and rearranged NFKB2 treated with Id and confirm that NFKB2 rearrangement is associated with reduce response rate. III. To compare the responses rate at 4 cycles of patients with rearranged NFKB2 treated with Id or IRd and confirm that adding lenalidomide increases the response rate in this population. SECONDARY OBJECTIVES: I. To determine time to treatment failure (TTF). II. To determine the frequency and severity of adverse events (AE) in IRd treated cohort. III. To identify novel transcribed mutations associated with Id and IRd resistance in patients with multiple myeloma (MM). IV. To determine the prevalence of NFKB2 rearrangement in relapsed/refractory MM patients screened in the study. V. To determine the prevalence of NFKB2 rearrangement according to the type of previous therapies received in all patients screened in the study. VI. To determine the toxicity profile of the study drugs according to the presence of NFKB2 rearrangement. VII. Delineate transcribed mutations associated with relapse or refractoriness to Id or IRd treatment by ribonucleic acid (RNA)-sequencing. OUTLINE: ARM A (UNMUTATED NFKB2 REARRANGEMENT): Patients receive ixazomib orally (PO) on days 1, 8, and 15 and dexamethasone PO on days 1, 8, 15, and 22. Patients with mutated NFKB2 rearrangement are randomized in to 1 of 2 treatment arms. ARM B (MUTATED NFKB2 REARRANGEMENT): Patients receive ixazomib and dexamethasone as in arm A. ARM C (MUTATED NFKB2 REARRANGEMENT): Patients receive ixazomib and dexamethasone as in arm A and lenalidomide PO daily on days 1-21. In all arms, cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may proceed to autologous stem cell transplant after 4 cycles of treatment. After completion of study, patients are followed up monthly. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02765854
Study type Interventional
Source Emory University
Contact
Status Active, not recruiting
Phase Phase 2
Start date September 1, 2016
Completion date December 1, 2024

See also
  Status Clinical Trial Phase
Completed NCT02948283 - Metformin Hydrochloride and Ritonavir in Treating Patients With Relapsed or Refractory Multiple Myeloma or Chronic Lymphocytic Leukemia Phase 1
Terminated NCT04956302 - Panobinostat in Combination With Daratumumab, Bortezomib and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma Phase 1
Completed NCT01527045 - Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies Phase 2
Completed NCT01689987 - Hydroxychloroquine, Cyclophosphamide, Dexamethasone, and Sirolimus in Treating Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02506959 - Panobinostat, Gemcitabine Hydrochloride, Busulfan, and Melphalan Before Stem Cell Transplant in Treating Patients With Refractory or Relapsed Multiple Myeloma Phase 2
Active, not recruiting NCT03457142 - Abatacept, Ixazomib Citrate, and Dexamethasone in Treating Patients With Multiple Myeloma Resistant to Chemotherapy Phase 2
Recruiting NCT03246906 - Comparison of Triple GVHD Prophylaxis Regimens for Nonmyeloablative or Reduced Intensity Conditioning Unrelated Mobilized Blood Cell Transplantation Phase 2
Withdrawn NCT03328936 - Study of Personalized Melphalan Dosing in the Setting of Autologous Transplant Phase 2
Recruiting NCT05514990 - Bortezomib and Pembrolizumab With or Without Pelareorep for the Treatment of Relapsed or Refractory Multiple Myeloma, AMBUSH Trial Phase 1/Phase 2
Completed NCT01989598 - Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Relapsed or Refractory Multiple Myeloma Phase 2
Completed NCT03605719 - Dexamethasone, Carfilzomib, & Nivolumab With Pelareorep for Relapsed/Refractory Multiple Myeloma Phase 1
Completed NCT01903811 - S1304, Carfilzomib and Dexamethasone for Treating Patients With Relapsed or Refractory Myeloma Phase 2
Recruiting NCT05391750 - Venetoclax and Tocilizumab for the Treatment of Patients With Relapsed or Refractory t(11;14) Multiple Myeloma Phase 1
Completed NCT00789776 - Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation, and Donor Bone Marrow Transplant Followed by Donor Natural Killer Cell Therapy, Mycophenolate Mofetil, and Tacrolimus in Treating Patients With Hematologic Cancer Phase 1/Phase 2
Completed NCT02593123 - Adoptive Immunotherapy in Relapsed Hematological Malignancy: Early GVHD Prophylaxis Phase 2
Terminated NCT04407442 - Daratumumab, Azacitidine, and Dexamethasone for Treatment of Patients With Recurrent or Refractory Multiple Myeloma Previously Treated With Daratumumab Phase 2
Completed NCT00450814 - Vaccine Therapy With or Without Cyclophosphamide in Treating Patients With Recurrent or Refractory Multiple Myeloma Phase 1/Phase 2
Completed NCT03338972 - Immunotherapy With BCMA CAR-T Cells in Treating Patients With BCMA Positive Relapsed or Refractory Multiple Myeloma Phase 1
Recruiting NCT04508790 - Leflunomide, Pomalidomide, and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma Phase 2
Recruiting NCT05363111 - Radioimmunotherapy (111Indium/225Actinium-DOTA-daratumumab) for the Treatment of Relapsed/Refractory Multiple Myeloma Phase 1