Bortezomib (VELCADE), Cladribine and Rituximab (VCR) in Mantle Cell Lymphoma: A Phase I/II Study (PSHCI 10-011)
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.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary Outcome Dose Limiting Tolerability
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 .
2 years
Yes
Elliot M Epner, MD PhD
Principal Investigator
Milton S. Hershey Medical Center
United States: Institutional Review Board
PSHCI 10-011
NCT01439750
May 2012
October 2015
Name | Location |
---|---|
Penn State Milton S. Hershey Medical Center | Hershey, Pennsylvania 17033 |
Penn State University | Hershey, Pennsylvania 17033 |