NCT02206425

Ixazomib as a Replacement for Carfilzomib and Bortezomib for Multiple Myeloma Patients

A Phase 1/2 Study of Ixazomib as a Replacement for Bortezomib or Carfilzomib for Multiple Myeloma (MM) Patients Recently Relapsed or Refractory to Their Last Combination Regimen Containing Either Bortezomib or Carfilzomib

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 45 (actual)
• Sponsor: Oncotherapeutics · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical research study is to evaluate the safety and effectiveness (good and bad effects) of ixazomib given as part of a combination therapy to treat subjects with relapsed (subjects whose disease came back) or refractory (subjects whose disease did not respond to past treatment) multiple myeloma. More specifically, the study is focused on subjects who were previously treated with bortezomib (Velcade®) or carfilzomib (Kyprolis®) and showed worsening of their myeloma while receiving either one of these drugs in combination therapy. This study is a Phase I/II. Ixazomib is an investigational drug, which means that ixazomib is currently being tested and is not yet approved by the United States Food and Drug Administration (FDA) for subjects with relapsed or refractory multiple myeloma. Ixazomib is a new study drug that belongs to the same class as bortezomib and carfilzomib; however, unlike bortezomib and carfilzomib, ixazomib is taken by mouth. Current studies investigating ixazomib are demonstrating that it is as safe as bortezomib and effective for the treatment of multiple myeloma both on its own and in combination with other multiple myeloma medications, such as lenalidomide and dexamethasone, or prednisone and melphalan.

Detailed description

This is a phase 1/2, intra-patient, multicenter, open-label and non-randomized study to evaluate the efficacy and safety of ixazomib as a replacement for bortezomib or carfilzomib among multiple myeloma (MM) patients who have failed proteasome inhibitor (PI)-containing combination regimens. Patients will receive ixazomib once a week in place of bortezomib or carfilzomib in combination with an alkylating agent (melphalan or cyclophosphamide), anthracycline (pegylated doxorubicin \[PLD\]), immunomodulatory agent (lenalidomide, pomalidomide), ascorbic acid and/or a glucocorticosteroid (dexamethasone, prednisone or methylprednisolone) administered using the same dose(s) and schedule(s) as the last PI-containing regimen that the patients had received and failed. The total number of different prior bortezomib- or carfilzomib-containing regimens that will be evaluated is 10, reflecting those commonly used in the community as follows: * bortezomib + melphalan + prednisone * bortezomib + cyclophosphamide + ascorbic acid * bortezomib + cyclophosphamide + dexamethasone * bortezomib + PLD + dexamethasone * bortezomib + dexamethasone * carfilzomib + dexamethasone * bortezomib + lenalidomide + dexamethasone * bortezomib + pomalidomide + dexamethasone * carfilzomib + lenalidomide + dexamethasone * carfilzomib + pomalidomide + dexamethasone This study will enroll 60 patients who are refractory to a bortezomib- or carfilzomib-containing combination regimen, as demonstrated by progressive disease (PD) while being treated, or who have relapsed within 8 weeks from the last dose of bortezomib or carfilzomib in their last PI-containing combination regimen. Ixazomib will replace bortezomib or carfilzomib using the same PI-containing regimen the patients failed.The study will consist of: 1) a screening period; 2) up to eight 28-day treatment cycles; 3) a maintenance period; 4) a final assessment to occur 28 days after the end of the last treatment cycle; and 5) a follow-up period. Ixazomib will be administered PO at 4 mg on Days 1, 8 and 15 of a 28-day cycle to patients enrolled in seven regimens (bortezomib + melphalan + prednisone, bortezomib + dexamethasone, carfilzomib + dexamethasone, bortezomib + lenalidomide + dexamethasone, bortezomib + pomalidomide + dexamethasone, carfilzomib + lenalidomide + dexamethasone, carfilzomib + pomalidomide + dexamethasone). Subjects on those regimens receiving 4 mg of ixazomib from the beginning of the trial will continue to do so for the length of the study, unless they suffer from adverse events requiring dose reductions. For the other three regimens, bortezomib + cyclophosphamide + dexamethasone, bortezomib + cyclophosphamide + ascorbic acid, and bortezomib + PLD + dexamethasone, the MTD for ixazomib is unknown and intra-patient dose escalation will be performed to determine the specific MTD for each of them. For these three regimens, ixazomib will be administered on Days 1, 8 and 15 of a 28-day cycle at a starting dose of 3 mg in Cycle 1, and then intra-patient dose-escalation will proceed to 4 mg in Cycle 2. All other agents will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Melphalan	Melphalan will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
DRUG	Prednisone	Prednisone will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
DRUG	Cyclophosphamide	Cyclophosphamide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
DRUG	Dexamethasone	Dexamethasone will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
DIETARY_SUPPLEMENT	Ascorbic acid	Vitamin C will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
DRUG	PLD	Pegylated liposomal doxorubicin will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
DRUG	Lenalidomide	Lenalidomide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).
DRUG	Pomalidomide	Pomalidomide will be administered at the same schedule and dose intensity as those of the last PI-containing treatment the patient failed (it varies with each patient).

Timeline

• Start date: 2014-09-01
• Primary completion: 2018-01-19
• Completion: 2018-03-06
• First posted: 2014-08-01
• Last updated: 2023-10-31

Locations

12 sites across 1 country: United States