Phase I / II Study Of Carfilzomib (CFZ) Intensification Early After Autologous Transplantation (AHCT) For Plasma Cell Myeloma
Background:
- Despite very significant progress in therapy for plasma cell myeloma (PCM) in the last
decade, the disease remains mostly incurable.
- High-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT)
continues to be a critical component of early treatment for PCM, but it is clear that
the disease is not eradicated by the present high-dose therapy strategy, while
intensifying the preparative regimen has, to this day, resulted in either no
improvement in disease control or increased toxicity.
- Carfilzomib (CFZ) is a newer proteasome inhibitor with increased activity and a safer
toxicity profile than bortezomib in PCM. The favorable toxicity profile makes it a
likely candidate for increasing anti-PCM drug exposure in the early post-AHCT period.
Objectives:
Primary Objectives
-Evaluate feasibility and toxicity of an increasing number of doses of CFZ administered in
the early period post-AHCT for PCM
Secondary Objective
- Evaluate the immune reconstitution post-AHCT following CFZ therapy
- Evaluate the effects of the addition of CFZ in the early post-AHCT period on the
response rate at day 100 post-AHCT
Eligibility:
- Newly diagnosed subjects with PCM following induction therapy
- Subjects with documentation of persistent/refractory disease who have received no more
than 2 salvage regimens following relapse and who have not undergone AHCT
- Adequate organ functions with no major co-morbidity
- Age greater than 18 years and less than or equal to 75 years
Design:
- Phase I/II study on the backbone of high-dose melphalan on day -2 pre-AHCT
- Addition of an increasing number of doses of CFZ in the early post-AHCT period
introduced in a step-wise fashion in 3 successive cohorts of 3 to 15 subjects:
Cohort 1: add CFZ 20 mg/m2 on days +1, +2
Cohort 2 : add CFZ 20 mg/m2 on days: +1, +2, +8, +9
Cohort 3: add CFZ 20 mg/m2 on days: +1, +2, +8, +9 and add an early post-AHCT consolidation
following
engraftment: CFZ 20 mg/m2 given on days 42-43 then CFZ 56 mg/m2 given on days 49-50, 56-57,
then on days 70-71, 77-78 and 84-85
-Dose-limiting toxicity, incidence of engraftment failure and treatment-related mortality
are the objects of early stopping rules for safety purposes
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Engraftment failure transplant related mortality
Claude Sportes, M.D.
Principal Investigator
National Cancer Institute (NCI)
United States: Federal Government
120179
NCT01658904
July 2012
June 2017
Name | Location |
---|---|
National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |