Trial of Romidepsin and Bortezomib for Multiple Myeloma
- Registration Number
- NCT00765102
- Lead Sponsor
- Celgene
- Brief Summary
This is a phase II, open-label, multicenter, dual-strata study designed to evaluate the efficacy and safety of IV romidepsin given in combination with IV bortezomib for multiple myeloma (MM) patients with refractory or relapsed disease. Patients will be enrolled into one of two strata, bortezomib-resistant or bortezomib non-resistant.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 32
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Romidepsin + Bortezomib Bortezomib Romidepsin was given as an infusion on Days 1, 8 and 15 of each 28-day cycle. Bortezomib was administered twice a week for two consecutive weeks (Days 1, 4, 8 and 11) followed by a 17-day rest period. Patients were treated to a maximum response plus two additional cycles or a maximum of eight cycles. Romidepsin + Bortezomib Romidepsin Romidepsin was given as an infusion on Days 1, 8 and 15 of each 28-day cycle. Bortezomib was administered twice a week for two consecutive weeks (Days 1, 4, 8 and 11) followed by a 17-day rest period. Patients were treated to a maximum response plus two additional cycles or a maximum of eight cycles.
- Primary Outcome Measures
Name Time Method Count of Participant Best Overall Response As Assessed by the Investigator up to 8 months Complete Response: disappearance of monoclonal protein from blood and urine, and disappearance of soft tissue plasmacytomas, \<5% plasmas cells in marrow and no increase of lytic bone lesions.
Very Good Partial Response: disappearance of plasmacytomas, no increase of lytic bone lesions, serum and urine M-protein not detectable by immunofixation, other.
Partial Response: \>=50% decrease in serum monoclonal protein, and in soft tissue plasmacytomas, no increase of lytic bone lesions, other.
Minimal Response (MR): ≥ 25% to ≤ 49% decrease in serum monoclonal protein, and in size of plasmacytomas, no increase of lytic bone lesions, other.
Stable Disease: Less than MR, but not PD
Progressive Disease(PD):\>25% increase in serum monoclonal paraprotein, or \>25% plasma cells in marrow, or \>25% increase in 24-hour urinary light chain excretion or increase in existing lytic bone lesions or soft tissue plasmacytomas or new bone lesions or soft tissue plasmacytomas, or hypercalcemia.
- Secondary Outcome Measures
Name Time Method Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) Day 1 (cycle 1): 1 hour prior to romidepsin administration, 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours after initiation of romidepsin infusion AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞) of Romidepsin based on plasma samples.
Total Clearance (CL) Day 1 (cycle 1): 1 hour prior to romidepsin administration, 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours after initiation of romidepsin infusion Total clearance of Romidepsin
Participants With Treatment-emergent Adverse Events (TEAEs) up to 9 months Counts of participants with TEAEs, and subset by relation to drug, grade of severity, serious, TEAEs leading to discontinuation or leading to death. AEs were graded for severity according to the National Cancer Institute Common Terminology Criteria (NCI CTCAE), V 3.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe (prevents normal everyday activities); Grade 4: Life-threatening or disabling; Grade 5: Death.
Time to Maximum Observed Concentration (Tmax) Day 1 (cycle 1): 1 hour prior to romidepsin administration, 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours after initiation of romidepsin infusion Time to maximum observed concentration of Romidepsin
Kaplan Meier Estimate for Time to Progression Assessed by the Investigator up to month 8 Time to progression of disease is defined as the time from initiation of therapy to progressive disease as assessed by the investigator.
Progressive Disease(PD):\>25% increase in serum monoclonal paraprotein, or \>25% plasma cells in marrow, or \>25% increase in 24-hour urinary light chain excretion or increase in existing lytic bone lesions or soft tissue plasmacytomas or new bone lesions or soft tissue plasmacytomas, or hypercalcemia.
Disease progression for participants relapsing from a complete response: reappearance of serum or urinary paraprotein on imunofixation, \>= 5% plasma cells in the bone marrow aspirate or biopsy, increase in existing lytic bone lesions or soft tissue plasmacytomas or new bone lesions or soft tissue plasmacytomas, development of hypercalcemia.Maximum Observed Concentration (Cmax) Day 1 (cycle 1): 1 hour prior to romidepsin administration, 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours after initiation of romidepsin infusion Maximum observed concentration of Romidepsin
Total Volume of Distribution (Vz) Day 1 (cycle 1): 1 hour prior to romidepsin administration, 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours after initiation of romidepsin infusion Total volume of distribution of Romidepsin
Kaplan Meier Estimates for Progression-free Survival Assessed by the Investigator up to month 8 Progression-free survival is the time from initiation of therapy to progressive disease, removal from study for any reason, death from any cause, or the last follow-up visit, whichever occurs first.
Progressive Disease(PD):\>25% increase in serum monoclonal paraprotein, or \>25% plasma cells in marrow, or \>25% increase in 24-hour urinary light chain excretion or increase in existing lytic bone lesions or soft tissue plasmacytomas or new bone lesions or soft tissue plasmacytomas, or hypercalcemia.
Disease progression for participants relapsing from a complete response: reappearance of serum or urinary paraprotein on imunofixation, \>= 5% plasma cells in the bone marrow aspirate or biopsy, increase in existing lytic bone lesions or soft tissue plasmacytomas or new bone lesions or soft tissue plasmacytomas, development of hypercalcemia.Terminal Half-life (t1/2) Day 1 (cycle 1): 1 hour prior to romidepsin administration, 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours after initiation of romidepsin infusion Terminal half-life of Romidepsin
Kaplan Meier Estimate for Time to Response Assessed by the Investigator up to month 8 The time to the first response is defined as the time from the initiation of therapy to the first evidence of a confirmed response (complete response, very good partial response, partial response or minimal response).
Complete Response: disappearance of monoclonal protein from blood and urine, and disappearance of soft tissue plasmacytomas, \<5% plasmas cells in marrow and no increase of lytic bone lesions.
Very Good Partial Response: disappearance of plasmacytomas, no increase of lytic bone lesions, serum and urine M-protein not detectable by immunofixation, other.
Partial Response: \>=50% decrease in serum monoclonal protein, and in soft tissue plasmacytomas, no increase of lytic bone lesions, other.
Minimal Response (MR): ≥ 25% to ≤ 49% decrease in serum monoclonal protein, and in size of plasmacytomas, no increase of lytic bone lesions, other.Kaplan Meier Estimate for Duration of Response Assessed by the Investigator up to month 8 Duration of response is defined as the time from first response to progressive disease as assessed by the investigator.
Progressive Disease(PD):\>25% increase in serum monoclonal paraprotein, or \>25% plasma cells in marrow, or \>25% increase in 24-hour urinary light chain excretion or increase in existing lytic bone lesions or soft tissue plasmacytomas or new bone lesions or soft tissue plasmacytomas, or hypercalcemia.
Disease progression for participants relapsing from a complete response: reappearance of serum or urinary paraprotein on imunofixation, \>= 5% plasma cells in the bone marrow aspirate or biopsy, increase in existing lytic bone lesions or soft tissue plasmacytomas or new bone lesions or soft tissue plasmacytomas, development of hypercalcemia.Kaplan Meier Estimates for Overall Survival up to month 8 Overall survival is the time from initiation of therapy to death from any cause.
Trial Locations
- Locations (12)
Loma Linda University Cancer Center
🇺🇸Loma Linda, California, United States
Santa Barbara Hematology Oncology Medical Group, Inc.
🇺🇸Santa Barbara, California, United States
Desert Cancer Care, Inc
🇺🇸Rancho Mirage, California, United States
Virginia Mason Medical Centre
🇺🇸Seattle, Washington, United States
Georgia Cancer Specialists I, PC
🇺🇸Atlanta, Georgia, United States
James R Berenson, MD, Inc.
🇺🇸West Hollywood, California, United States
Mecklenburg Medical Group
🇺🇸Charlotte, North Carolina, United States
Dallas Oncology Consultants, P.A.
🇺🇸Duncanville, Texas, United States
Oncology Consultants, P.A
🇺🇸Houston, Texas, United States
Central Utah Clinic, PC
🇺🇸Provo, Utah, United States
Center for Cancer and Blood Disorders
🇺🇸Bethesda, Maryland, United States
Baylor Sammons Cancer Center
🇺🇸Dallas, Texas, United States