Alemtuzumab and Low-Dose Cyclosporine in Treating Patients With Severe Aplastic Anemia or Acquired Marrow Failure

Sponsor

Federico II University (Other)

Overall Status

Unknown status

CT.gov ID

NCT00895739

Collaborator

(none)

Enrollment

Location

Study Details

Study Description

Brief Summary

RATIONALE: Immunosuppressive therapies, such as alemtuzumab and cyclosporine, may improve bone marrow function and increase blood cell counts. Giving alemtuzumab together with cyclosporine may be an effective treatment for severe aplastic anemia or acquired marrow failure.

PURPOSE: This phase II trial is studying the side effects of giving alemtuzumab together with cyclosporine and to see how well it works in treating patients with severe aplastic anemia or acquired marrow failure.

Condition or Disease	Intervention/Treatment	Phase
Nonmalignant Neoplasm	Biological: alemtuzumab Drug: cyclosporine	Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the safety of alemtuzumab and low-dose cyclosporine, as defined by occurrence of adverse effects, in patients with severe aplastic anemia or single lineage acquired marrow failure.
Determine the efficacy of this regimen, in terms of overall survival, hematological response (partial and complete response, including time to response) and failure-free survival (failure is defined as no response, chronic treatment-maintained response, or relapse), in these patients.

Secondary

Evaluate the incidence of adverse effects after treatment.
Evaluate the long-term safety of alemtuzumab treatment.
Determine the time to achieve a complete hematological response.
Determine the proportion of patients maintaining hematological response free of any treatment.
Determine the incidence of relapse in responding patients.
Determine the incidence of severe infections.
Determine the requirement for IV antibiotics and antifungal therapy.
Determine the requirement for red cell and platelet transfusion.
Determine the incidence of CMV reactivation.
Determine the kinetics of immune reconstitution.
Determine the incidence of paroxysmal nocturnal hemoglobinuria clone (lymphoid or myeloid) development.
Determine the incidence of clonal evolution (i.e., karyotypic abnormalities or secondary myelodysplasia/leukemia).

OUTLINE: Patients receive alemtuzumab subcutaneously on days 1-5*. Patients also receive oral cyclosporine beginning on day 7 and continuing for ≥ 180 days, followed by a taper according to clinical condition.

NOTE: *Patients with single lineage aquired marrow failure receive alemtuzumab on days 1-4.

After completion of study therapy, patients will be followed up every 3 months for up to 2 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Non-Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Alemtuzumab and Low-Dose Cyclosporine-A as Alternative Immunosuppressive Treatment for Severe Aplastic Anemia (SAA) and Single-Lineage Aplastic Patients

Study Start Date :

Jun 1, 2006

Outcome Measures

Primary Outcome Measures

Safety, as defined by occurrence of adverse effects []
Overall survival []
Hematologic response (partial and complete response, including time to response) []
Failure-free survival (failure is defined as no response, chronic treatment-maintained response, or relapse) []

Secondary Outcome Measures

Incidence of adverse effects after treatment []
Long-term safety of alemtuzumab treatment []
Time to achieve a complete hematological response []
Proportion of patients maintaining hematological response free of any treatment []
Incidence of relapse in responding patients []
Incidence of severe infections []
Requirement for IV antibiotics and antifungal therapy []
Requirement for red cell and platelet transfusion []
Incidence of CMV reactivation []
Kinetics of immune reconstitution []
Incidence of paroxysmal nocturnal hemoglobinuria (PNH) clone (lymphoid or myeloid) development []
Incidence of clonal evolution (i.e., karyotypic abnormalities or secondary myelodysplasia/leukemia) []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
Severe or very severe aplastic anemia, as defined by the following criteria:
Meets ≥ 2 of the following criteria:
Absolute neutrophil count < 0.5 x 10^{9/L (severe) or < 0.2 x 10}9/L (very severe)
Platelet count < 20 x 10^9/L
Reticulocyte count < 20 x 10^9/L
Hypocellular bone marrow (< 30% cellularity) without evidence of fibrosis or malignant cells
Single lineage acquired marrow failure (e.g., pure red cell aplasia, agranulocytosis, amegakaryocytic thrombocytopenia)
Paroxysmal nocturnal hemoglobinuria clone allowed
Failed first-line therapy with antithymocyte globulin (ATG) and cyclosporine OR not eligible for ATG-based studies
Failure is defined as lack of hematological response, requirement for chronic immunosuppressive treatment to sustain response, or relapse
Not eligible for a low-risk stem cell transplantation
No evidence of risky myelodysplastic syndromes (i.e., IPSS 3-4), as defined by the presence of marrow blast excess or karyotypic abnormalities, or other primitive marrow disease
No history of constitutional aplastic anemia (e.g., Fanconi anemia or dyskeratosis congenita)