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A Phase 1/2 Study of Alefacept, a CD2 Receptor Antagonist in Patients With Relapsed/Refractory Aplastic Anemia

Phase 1
18 Years
Not Enrolling
Aplastic Anemia

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Trial Information

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
of study.

Inclusion Criteria:

1. Fulfilled criteria for diagnosis of either moderate (mAA) or severe aplastic anemia
(sAA) at the time of initial diagnosis defined per protocol.

2. Patient with a history sAA must have had an incomplete response at least 3 months
following treatment with ATG/CsA, or they must have relapsed following an initial
response to treatment.

3. Patient must not be receiving any cyclosporine or any other T cell immunosuppressive
agents within 4 weeks of study entry.

4. Patients must have organ function as defined below:

- total bilirubin within normal institutional limits (NV: 0.0-1.5 mg/dL)

- AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal AST (NV: 7-40
U/L); ALT (NV: Male 5-50 U/L; Female 0-45 U/L)

- creatinine within normal institutional limits (NV: Age 18 0.4-1.3 mg/dL; 19-99
years old 0.7-1.4 mg/dL) OR

- creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels
above institutional normal.

5. Peripheral blood counts at the time of enrollment must include at least one of the
following: Hgb <9 g/dL or red blood cell (RBC) transfusion dependence, ANC <1000/µl,
or platelet count of <60,000/µL.

6. Women of child-bearing potential and men must agree to use adequate contraception
defined per protocol.

7. Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

1. Patients may not be receiving any other investigational agents (other than
hematopoietic growth factors) within 4 weeks of study entry.

2. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Alefacept.

3. Current diagnosis of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS),
Fanconi's anemia, Dyskeratosis Congenita (DC) or other hereditary forms of AA.

4. Psychiatric, addictive or any other disorder that compromises ability to give a truly
informed consent.

5. Age <18 years.

6. ECOG performance status >2 (Karnofsky <60%, see Appendix A).

7. Malignancy other than non-melanoma skin cancer within the last 2 years.

8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection (defined as uncontrolled infection requiring IV antibiotics, invasive
fungal infection and progressive CMV viremia), symptomatic congestive heart failure
(NYH class III and IV), unstable angina pectoris, or cardiac arrhythmia.

9. Pregnant or breastfeeding women.

10. HIV-positive patients on combination antiretroviral therapy.

11. Patients who have previously received systemic chemotherapy and/ or radiation

12. Patients who previously underwent allogeneic hematopoietic stem cell transplant.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To measure the number of dose limiting toxicities (DLTs) as a determination of the maximum tolerable dose (MTD).

Outcome Description:

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.

Outcome Time Frame:

Every 12 weeks

Safety Issue:


Principal Investigator

Ramon V. Tiu, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

May 2011

Completion Date:

November 2017

Related Keywords:

  • Aplastic Anemia
  • Alefacept
  • Amevive
  • Aplastic Anemia
  • Moderate to Severe Aplastic Anemia
  • Anemia
  • Anemia, Aplastic



Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Cleveland, Ohio  44195