Clinical Trial: Bortezomib (VELCADE), Cladribine and Rituximab (VCR) in Mantle Cell Lymphoma (PSHCI 10-011)

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Bortezomib (VELCADE), Cladribine and Rituximab (VCR) in Mantle Cell Lymphoma: A Phase I/II Study (PSHCI 10-011)

Brief Summary: This is a phase I/II trial of bortezomib, cladribine, and rituximab in newly diagnosed and relapsed mantle cell lymphoma (MCL). The phase I component has three dose levels of cladribine (3 mg/m2, 4 mg/m2, and 5 mg/m2) and is designed as a traditional dose-escalation study in which cohorts of 3 patients are evaluated for the incidence of dose-liming toxicity (DLT) at each dose level. Once the maximum tolerated dose (MTD) is determined, a phase II component with 2 arms will begin. One arm will enroll newly diagnosed MCL patients and one arm will enroll relapsed MCL patients. Each arm is a single-stage, fixed sample size study and will be accrued and analyzed separately. The phase I and II data will also be analyzed separately.

Detailed Summary:

The phase I portion of the study is a standard dose-escalation schemed designed to determine the maximum tolerated dose (MTD) of the combination of bortezomib, cladribine, and rituximab therapy. The MTD is defined as the dose level in which ≤1 out of 6 patients have dose-limiting toxicity (DLT). Three patients are enrolled on a dose level. If 0 out of 3 patients have DLT, then the next set of 3 patients are enrolled at the next highest dose level. If ≥2 out of 3 patients have DLT, then the MTD will have been exceeded and dose escalation will cease. Three additional patients will be enrolled at the next lowest dose level if only 3 were treated previously at that level. If 1 out of 3 patients have DLT, then the next set of 3 patients will be treated at the same dose level. If ≤1 out of 6 patients treated at that dose level have DLT, then the next set of patients will be treated at the next higher dose level. If ≥2 out of 6 patients treated at that dose level have DLT, then the MTD will have been exceeded and dose escalation will cease. Three additional patients will be treated at the next lowest dose level if only 3 were treated previously at that level. This phase I study will use 3 dose levels of cladribine (3 mg/m2, 4 mg/m2, and 5 mg/m2), with 3 mg/m2 being the starting dose level. DLTs will be assessed at the completion of the first 2 cycles of cladribine and rituximab.

Phase II Design: The phase II portion of the study is a two-arm, single-stage design with no interim analysis. One arm will accrue newly diagnosed patients, and one arm will accrue relapsed patients. In each arm, the progression-free survival rate at 2 years will be used as the primary endpoint for determining whether the treatment is sufficiently active in each arm. No comparisons will be made between the arms.


Sponsor: Milton S. Hershey Medical Center

Current Primary Outcome: Primary Outcome Dose Limiting Tolerability [ Time Frame: 2 years ]

Dose Limiting Tolerability as measured by CTCAEv.4 criteria and to evaluate progression free survival in patients treated with VCR in the Phase 1 portion .


Original Primary Outcome: Primary Outcome Dose Limiting Tolerability [ Time Frame: 2 years ]

Dose Limiting Tolerability as measured by CTCAEv.3 criteria and to evaluate progression free survival in patients treated with VCR in the Phase 1 portion .


Current Secondary Outcome: Secondary Outcome objective response rates [ Time Frame: 7 months ]

Estimate objective response rates of the VCR regimen in B cell malignancies where response to therapy is assessed per the revised Cheson criteria (2007) and the overall survival of patients treated with this combination for the Phase 2 portion of the study.


Original Secondary Outcome: Same as current

Information By: Milton S. Hershey Medical Center

Dates:
Date Received: August 16, 2011
Date Started: May 2012
Date Completion: July 2017
Last Updated: January 26, 2017
Last Verified: January 2017