A Phase 1/2 Study of Alefacept, a CD2 Receptor Antagonist in Patients With Relapsed/Refractory Aplastic Anemia
1. Primary Objective
- To define the safety, tolerability, dose-limiting toxicities (DLT), of alefacept
in relapsed/ refractory aplastic anemia (AA).
- To evaluate the efficacy of alefacept in refractory/ relapsed AA by determining
overall response rates (ORR) which includes complete remission [CR] and partial
remission (PR) rates.
2. Secondary Objective
- To evaluate for predictive markers for response to Alefacept with relapsed/
refractory AA and evaluate its effect on the PNH clone. The effects of alefacept
in major populations of lymphocytes will be evaluated. The absolute numbers of
various T cell populations including CD3+ T cell, CD3+/CD4+ T cell, CD3+/CD8+,
CD57+ natural killer cell count and CD4/CD8 ratio will be measured as part of an
immunodeficiency panel by flow cytometry. The functional properties of T cells
will be evaluated by measuring markers of T cell activation and cytokine
production. The saturation of CD2 receptors with alefacept will be determined.
Occupied CD2 will not be detectable by competing antibody in-vitro. The expression
of CD2 within lymphocytes will be measured prior to the initiation of therapy and
every 2 weeks prior to and 30 minutes after the administration of alefacept. The
presence of a Paroxysmal Nocturnal Hemoglobinuria (PNH) clone in patients with AA
has been shown to correlate with increased response to immunosuppression25.
OUTLINE: This is an open-label, single center study. Patients will receive intravenous
Alefacept once weekly for a total of 12 weeks in the absence of disease progression or
unacceptable toxicity. After completion of the 12 week treatment, patients will go through
a 12 week observation period. After completion of the study, patients will be followed
periodically. The dose defined in the Phase 1 study will be used for the subsequent Phase 2
study. Four bone marrow biopsies will be taken at screening, week 13, week 24, and the end
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To measure the number of dose limiting toxicities (DLTs) as a determination of the maximum tolerable dose (MTD).
The dosing cohorts includes (Cohort -1= 5 mg IV weekly, Cohort 1= 7.5 mg IV weekly, Cohort 2= 10 mg IV weekly, and Cohort 3= 12.5 mg IV weekly). The MTD will be defined as the dose level that has maxiumum effectiveness with minimal toxicity.
Every 12 weeks
Ramon V. Tiu, M.D.
Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center
United States: Institutional Review Board
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center||Cleveland, Ohio 44195|