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

NCT ID: NCT00895739

Last Updated: 2013-08-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30

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.

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.

Conditions

Nonmalignant Neoplasm

Keywords

aplastic anemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

alemtuzumab

Intervention Type: BIOLOGICAL

cyclosporine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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)

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Not pregnant or nursing
• No active malignant tumor within the past 5 years
• Transaminases ≤ 3 times upper limit of normal (ULN)
• Albumin ≥ 1.5 g/L
• Creatinine ≤ 3 times ULN
• No CMV viremia, as defined by positive PCR or pp65 test
• No cardiac failure (i.e., ejection fraction < 35%)
• No other concurrent life-threatening disease (including HIV infection)

PRIOR CONCURRENT THERAPY:

• No prior allogeneic stem cell transplantation
• At least 2 weeks since prior cyclosporine or filgrastim (G-CSF)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federico II University

OTHER

Sponsor Role: lead

Principal Investigators

Bruno Rotoli, MD

Role: PRINCIPAL_INVESTIGATOR

Federico II University

Locations

Federico II University Medical School

Naples, , Italy

Site Status: RECRUITING

Countries

Italy

Facility Contacts

Bruno Rotoli, MD

Role: primary

Other Identifiers

CDR0000639649

Identifier Type: REGISTRY

Identifier Source: secondary_id

EU-20927

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2008-001151-22

Identifier Type: -

Identifier Source: secondary_id

UNMS-ALESAA

Identifier Type: -

Identifier Source: org_study_id