Melphalan and Panobinostat (LBH589) for the Treatment of Patients With Recurrent Multiple Myeloma
RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving melphalan together with panobinostat may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of melphalan when given together with panobinostat in treating patients with recurrent multiple myeloma.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Oral Melphalan Combined With LBH589 for Patients With Relapsed or Refractory Multiple Myeloma (MM)|
- Maximum Tolerated Dose (MTD) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Phase 1: to determine the MTD of panobinostat (LBH589) in combination with melphalan to be used in the Phase 2 portion of the study
- MTD [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Phase 1: to determine MTD of melphalan in combination with panobinostat to be used in the Phase 2 portion of the study
- Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) [ORR= Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR)]; CBR=ORR + Minimal Response (MR)] Following Treatment With Panobinostat and Melphalan [ Time Frame: 24 months ] [ Designated as safety issue: No ]Responses were evaluated according to criteria modified from those developed by Blade et al., 1998 The reference point for evaluating response improvement is the baseline. This baseline reference point is also valid when a patient has already achieved a response and transitions through into a better response grade.
- Duration of Response [ Time Frame: First evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death ] [ Designated as safety issue: No ]
- Time to Progression [ Time Frame: Time from the start of treatment to progressive disease ] [ Designated as safety issue: No ]
|Study Start Date:||July 2008|
|Study Completion Date:||December 2012|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Experimental: Melphalan and Panobinostat
Schedule A: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1-5 of week 1.
Toxicity led to the following changes in dose and schedule Schedule B1: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.
Schedule B2: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan POon days 1, 3 and 5 of week 1.
Schedule C: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1 and 2 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1 Schedule D1: 15 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.
Schedule D2: 15 mg/daily LBH589 PO and 0.10 mg/kg melphalan PO on days 1, 3 and 5 of week 1.
Schedule D3: 20 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.
Same as above
Other Name: Phenylalanine mustard, AlkeranDrug: Panobinostat
Other Name: LBH589
- To establish the maximum tolerated dose (MTD) and determine the dose-limiting toxicities (DLT) of panobinostat in combination with melphalan in patients with relapsed or refractory multiple myeloma. (Phase I)
- To determine the dose of this regimen to be used in the Phase II portion of the study. (Phase I)
- To determine the efficacy as evidenced by the response rate (combined complete response, very good partial response, partial response, and minimal response) in patients treated with this regimen. (Phase II)
- To obtain preliminary evidence of efficacy of the combination of LBH589 and melphalan for patients with relapsed or refractory multiple myeloma. (Phase I)
- To determine the safety and tolerability of this regimen in these patients. (Phase II)
- To determine time to disease progression, time to response, and duration of response in patients treated with this regimen. (Phase II)
- To determine progression-free survival and overall survival of patients treated with this regimen. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II study.
Patients receive oral panobinostat once daily on days 1, 3, 5, 8, 10, and 12 and oral melphalan once daily on days 1, 3 and 5. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00743288
|United States, California|
|Comprehensive Blood and Cancer Center|
|Bakersfield, California, United States, 93309-0633|
|James R. Berenson MD, Incorporated|
|West Hollywood, California, United States, 90069|
|United States, Colorado|
|Rocky Mountain Cancer Centers - Denver Midtown|
|Denver, Colorado, United States, 80218|
|United States, Maryland|
|Center for Cancer and Blood Disorders|
|Bethesda, Maryland, United States, 20817|
|Principal Investigator:||James R. Berenson, MD||Oncotherapeutics|