Phase I/II Study of the Combination of Panobinostat and Carfilzomib in Patients With Relapsed/Refractory Multiple Myeloma
This is an open-label; non-randomized Phase I/II study of patients with relapsed or
refractory multiple myeloma.
The Phase I study will determine the MTD of the combination of carfilzomib and panobinostat.
The Phase I portion will follow a standard dose escalation design, beginning with dose
level 1 (see Table 2). Patients will be assessed for dose-limiting toxicity (DLT) at each
visit during Cycle 1 prior to receiving treatment. Dose modifications will not be permitted
during Cycle 1 unless a patient experiences a DLT (see Section 5.2.2.). Treatment cycles
will be administered at 28-day intervals. Panobinostat will be administered orally three
times weekly during weeks 1 and 3 of each cycle (Days 1, 3, 5, 15, 17, 19). Carfilzomib
will be administered intravenously on Days 1, 2, 8, 9, 15, and 16 of each cycle. During
Cycle 1, the carfilzomib dose will be escalated after the Day 2 dose, if well tolerated.
A maximum of three dose levels will be evaluated.Approximately 24 patients will be enrolled
during the Phase I portion to establish the MTD.
In the Phase II portion of this study, patients with relapsed/refractory multiple myeloma
will receive treatment with the panobinostat and carfilzomib combination established during
Phase I. Patients will be reevaluated for response to treatment after each cycle (4
weeks). Patients with objective response or stable disease will continue treatment, with
subsequent reevaluations every 4 weeks, until disease progression or unacceptable toxicity
Up to 54 eligible patients will be treated in the Phase I/II study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
establish optimal doses of carfilzomib in mg/m^2 and panobinostat in mg in combination with each other (Phase I)
The Phase I study will determine the maximum tolerated dose (MTD) of the combination of carfilzomib and panobinostat. The Phase I portion will follow a standard dose escalation design, beginning with 3 patients on dose level 1: carfilzomib 20 mg/m2 IV D1, 2 / 27 mg/m2 IV D8, 9, 15, 16 for cycle 1 and panobinostat 20 mg D 1, 3, 5, 15, 17, 19 for cycle 1; carfilzomib 27 mg/m2 IV D 1, 2, 8, 9, 15, 16 for cycle 2 and panobinostat 20 mg D 1, 3, 5, 15, 17, 19 for cycle 2. Patients will be assessed for dose-limiting toxicity (DLT) at each visit during Cycle 1 prior to receiving treatment.
Jesus Berdeja, MD
Sarah Cannon Research Institute
United States: Food and Drug Administration
SCRI MM 27
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