The main purpose of this study is to see whether pomalidomide can help people with myeloma. Researchers also want to find out if pomalidomide is safe and tolerable.
There are two parts to this study: * Phase 1: To determine a safe dose of the medication cyclophosphamide in combination with pomalidomide and dexamethasone. * Phase 2: To see the difference in effectiveness of pomalidomide in combination with high dose dexamethasone with or without cyclophosphamide for the treatment of participants who have myeloma, which has relapsed to or become refractory (not responding) to prior treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
80
Pomalidomide at 4 mg by mouth (PO) as outlined in the treatment arms.
Dexamethasone at 40 mg (20 mg) PO as outlined in the treatment arms.
The dose escalation uses a standard "3x3" design: Ex: If none of the first 3 participants have a DLT, enter 3 participants at the next higher dose level. Once the maximum tolerated dose (MTD) of oral weekly cyclophosphamide in combination with pomalidomide and dexamethasone was determined, investigators proceeded with the second phase of the trial, a randomized phase II study comparing pomalidomide and dexamethasone with pomalidomide, dexamethasone and oral weekly cyclophosphamide delivered at the MTD determined in the phase I study.
University of California San Francisco
San Francisco, California, United States
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
Mount Sinai School of Medicine, The Tisch Cancer Institute
New York, New York, United States
Phase I - Maximum Tolerated Dose (MTD)
The maximum tolerated dose of oral weekly cyclophosphamide in milligrams (mg), in combination with pomalidomide and dexamethasone. Dose Escalation of Cyclophosphamide, orallly (PO) days 1, 8, 15 as follows: Level 1: 300 mg; Level 2: 400 mg; Level 3: 500 mg. The period for assessment of Dose Limiting Toxicity (DLT) is the first cycle (28 days). The following toxicities will be considered dose limiting if encountered only in the phase I portion of the study: Febrile neutropenia; Grade 3 or 4 non-hematologic toxicity related to treatment with pomalidomide or cyclophosphamide; Participants must have received optimal symptomatic treatment for Grade 3 or 4 nausea, vomiting, or diarrhea to be considered a DLT; Grade 4 transaminitis; Grade 3 transaminitis must be present for ≥ 7 days to be considered a DLT; Grade 4 thrombocytopenia for 7 or more days; Grade 4 neutropenia for 7 or more days.
Time frame: 28 Days
Phase II - Overall Response Rate (ORR)
Overall response, Minimal Remission (MR) or better per treatment arm, using the uniform response criteria by the International Myeloma Working Group (IMWG) of pomalidomide in combination with high dose dexamethasone with or without cyclophosphamide in participants with relapsed and refractory myeloma. In addition, Minimal response was incorporated in those response criteria as this is a valid endpoint in patients with relapsed or refractory myeloma. MR: 25-49% reduction in serum paraprotein and a 50-89% reduction in urine light chain excretion; A 25-49% reduction in the size of soft tissue plasmacytoma must be demonstrated is applicable.
Time frame: 36 Months
Phase II - Median Progression Free Survival (PFS)
Progression free survival per treatment arm. Progressive Disease (PD) requires one of the following, increase of greater than or equal to 25% from baseline in: Serum M-component; Urine M-component; The difference between involved and uninvolved sFLC levels; The size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia.
Time frame: 36 Months
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Phase II - Median Overall Survival (OS)
Overall survival per treatment arm. Overall survival is defined as the time from start of treatment to death of any cause.
Time frame: 36 Months
Phase II - Occurrence of Possibly Related Adverse Events (AEs)
Phase II: Participants with Grade 3 or 4 adverse events at least possibly related to the study treatment in 5% of participants in the Phase 2 portion, by AE category, assessed by the National Cancer Institute Common Terminology Criteria (NCI CTC) version 4.0.
Time frame: Up to 48 Months