Clinical trial NCT00743288
Conditions: Multiple Myeloma
Keywords: stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma refractory multiple myeloma
Sponsor: Oncotherapeutics
Start date: 2008-07-01; Completion date: 2012-12-01
Enrollment: 40 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
OBJECTIVES:

Primary

* 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)

Secondary

* 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.

Arms: arm 1: 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.
Interventions: intervention 1: Melphalan intervention 2: Panobinostat
Intervention descriptions: intervention 1: Same as above intervention 2: None

Protocol documents: