Bortezomib (Velcade) Plus Rituximab-HyperCVAD in Patients With Mantle Cell Lymphoma
The goal of this clinical research study is to learn if bortezomib (in combination with rituximab plus 2 different intensive chemotherapy regimens) can help to control the disease in patients with mantle cell lymphoma. The safety of these drug combinations will also be studied.
Mantle Cell Lymphoma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Bortezomib (Velcade) Plus Rituximab-HyperCVAD Alternating With Bortezomib Plus Rituximab-High Dose Methotrexate/Cytarabine in Patients With Untreated Aggressive Mantle Cell Lymphoma|
- Maximum Tolerated Dose (MTD) of Bortezomib Added to Combination of Rituximab, Methotrexate, and Cytarabine Alternating with Bortezomib, Rituximab-HyperCVAD [ Time Frame: Continual reassessment for toxicity with each 21 day cycle ] [ Designated as safety issue: Yes ]MTD defined as highest dose of bortezomib in which 2 or fewer patients in 6 treated experiences a dose limiting toxicity (DLT) among dose levels tested. DLT defined as a grade 3-4 non-hematologic toxicity that can not be ameliorated, prevented, or controlled with standard prophylactic therapy such as, but not limited to, nausea, vomiting, fatigue, diarrhea, constipation, low electrolyte levels, or tumor pain.
- Time to Failure (TTF) [ Time Frame: After 2, 21 day cycles ] [ Designated as safety issue: Yes ]Failure defined as recurrence/progression of disease or death from either disease or toxicity. Bayesian toxicity monitoring schema used to monitor severe toxicity profile in combined therapy. "Severe toxicity" per patient defined as at least two episodes of neutropenic fever during treatment courses, or grade 3-4 neuropathy during course of the patient's treatment. Time-to-event outcomes, including TTF, response duration, and overall survival, estimated using Kaplan-Meier method. Log-rank test performed to test difference in time-to-event distributions between patient groups. Cox proportional hazards model utilized to evaluate effects of covariates on time-to-event analysis.
|Study Start Date:||April 2007|
|Estimated Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
Experimental: Bortezomib + Cyclophosphamide/Rituximab
1st Combination, Cycles 1,3,5 & 7 (if needed): Bortezomib + Rituximab + Cyclophosphamide + Doxorubicin + Vincristine; 2nd Combination, Cycles 2,4,6 & 8 (if needed): Rituximab + Methotrexate + Cytarabine.
1st Combination = 1.3 mg/m^2 IV Push Over 3-5 Seconds Days 2 & 5; 2nd Combination = 0.7 mg/m^2 IV Push Days 1 & 6.
Other Names:Drug: Rituximab
375 mg/m^2 IV Over 6-8 Hours On Day 1 each cycle.
Other Name: RituxanDrug: Cyclophosphamide
1st Combination = 300 mg/m^2 IV Over 3 Hours Twice Daily Days 2,3,& 4.
Other Name: CytoxanDrug: Vincristine
1st Combination = 1.4 mg/m^2 (maximum 2 mg) IV Push Days 5 & 12.Drug: Methotrexate
2nd Combination = 200 mg/m^2 IV over 2 hours on Day 1, then 800 mg/m^2 IV over 22 hours on Day 2.Drug: Cytarabine
2nd Combination = 3g/m2 grams/m^2 IV over 2 Hours Twice a Day,On Days 3 & 4.
Other Names:Drug: Doxorubicin
Arm 1: 50 mg/m^2 IV Push Over 15-30 min on Day 5
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00477412
|United States, New Jersey|
|Hackensack University Medical Center|
|Hackensack, New Jersey, United States, 07601|
|United States, Texas|
|UT MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jorge Romaguera, MD||M.D. Anderson Cancer Center|