Phase 1b Multicenter Study of Carfilzomib With Lenalidomide and Dexamethasone in Relapsed Multiple Myeloma
To evaluate the safety and maximum tolerated dose (MTD) of carfilzomib in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma
Relapsed Multiple Myeloma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1b Multicenter Dose Escalation Study of Carfilzomib With Lenalidomide and Dexamethasone for Safety and Activity in Relapsed Multiple Myeloma|
- Number of Participants With Adverse Events (AEs) [ Time Frame: From the first dose of study drug until 30 days after the last dose; 1 to 52 months, with an average of 12 months. ] [ Designated as safety issue: Yes ]
Treatment-related are those AEs with possible or probable relationship to carfilzomib, lenalidomide or dexamethasone as assessed by the Investigator. The severity of each adverse event was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0, per the following: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death.
Serious adverse events were defined as AEs meeting one of the following: death, life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect in the offspring of an exposed participant, important medical events that may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above, or pregnancy or suspected pregnancy.
- Number of Participants With Dose-limiting Toxicities [ Time Frame: Cycle 1, 28 days ] [ Designated as safety issue: Yes ]
Dose-limiting toxicity was defined as any of the following events assessed as related to carfilzomib, lenalidomide, or dexamethasone: Nonhematologic
- ≥ Grade 2 neuropathy with pain
- ≥ Grade 3 nonhematologic toxicity (excluding nausea, vomiting, diarrhea, hyperglycemia due to dexamethasone, and rash due to lenalidomide)
- ≥ Grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal supportive therapy
- ≥ Grade 4 fatigue persisting > 7 days
- Treatment delay for toxicity > 21 days
- Grade 4 neutropenia (absolute neutrophil count [ANC] < 500/mm³) > 7 days
- Febrile neutropenia (ANC < 1,000/mm³ with fever ≥ 38.3ºC)
- Grade 4 thrombocytopenia (platelets < 25,000/mm³) for > 7 days despite holding treatment, or Grade 3 or 4 thrombocytopenia associated with bleeding
- Treatment delay for toxicity > 21 days.
The maximum-tolerated dose was defined as the dose level below which a drug-related DLT was observed in ≥ 33% of participants in a cohort.
|Study Start Date:||May 2008|
|Estimated Study Completion Date:||December 2015|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Experimental: Carfilzomib + Lenalidomide + Dexamethasone
Treatment during Cycles 1 through 12 consisted of carfilzomib (15, 20, or 20/27 mg/m²) on Days 1, 2, 8, 9, 15, and 16; lenalidomide (10, 15, 20, or 25 mg) on Days 1 to 21; and low-dose dexamethasone (40 mg) given 30 minutes to 4 hours before the carfilzomib dose on Days 1, 8, and 15, as well as on Day 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator's discretion.
Carfilzomib for Injection was administered intravenously over 10 minutes on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for the first 12 cycles. Each dose of Carfilzomib for Injection was normalized to body surface area.
Other Name: Kyprolis®Drug: Lenalidomide
Lenalidomide was administered orally on Days 1 to 21 of each 28-day cycle.
Other Name: REVLIMID®Drug: Dexamethasone
Dexamethasone 40 mg orally or intravenous equivalent was administered 30 minutes to 4 hours before carfilzomib on Days 1, 8, and 15, as well as on Day 22 of each 28-day cycle.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00603447
|United States, California|
|Pacific Shores Medical Group|
|Long Beach, California, United States, 90813|
|Cedars Sinai Medical Center|
|Los Angeles, California, United States, 90048|
|University of California San Francisco|
|San Francisco, California, United States, 94143|
|United States, Florida|
|H. Lee Moffitt Cancer Center & Research Institute|
|Tampa, Florida, United States, 33612|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, New Jersey|
|Hackensack University Medical Center|
|Hackensack, New Jersey, United States, 07601|
|United States, New York|
|New York, New York, United States, 10021|
|United States, Ohio|
|Gabrail Cancer Center|
|Canton, Ohio, United States, 44718|
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|United States, Washington|
|Fred Hutch Cancer Research Center|
|Seattle, Washington, United States, 98103-1204|
|United States, Wisconsin|
|Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|
|Jewish General Hospital|
|Montreal, Quebec, Canada, H3T 1E2|