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

Nonmalignant Neoplasm Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00895739
• Other study ID #: UNMS-ALESAA
• Secondary ID: CDR0000639649EU-
• Status: Recruiting
• Phase: Phase 2
• First received: May 7, 2009
• Last updated: August 9, 2013
• Start date: June 2006

Study information

• Verified date: May 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

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)

Study Design

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Aplastic
• Nonmalignant Neoplasm

Intervention

Biological:
• alemtuzumab

Drug:
• cyclosporine

Locations

Country	Name	City	State
Italy	Federico II University Medical School	Naples

Sponsors (1)

Lead Sponsor	Collaborator
Federico II University

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety, as defined by occurrence of adverse effects			Yes
Primary	Overall survival			No
Primary	Hematologic response (partial and complete response, including time to response)			No
Primary	Failure-free survival (failure is defined as no response, chronic treatment-maintained response, or relapse)			No
Secondary	Incidence of adverse effects after treatment			Yes
Secondary	Long-term safety of alemtuzumab treatment			Yes
Secondary	Time to achieve a complete hematological response			No
Secondary	Proportion of patients maintaining hematological response free of any treatment			No
Secondary	Incidence of relapse in responding patients			No
Secondary	Incidence of severe infections			No
Secondary	Requirement for IV antibiotics and antifungal therapy			No
Secondary	Requirement for red cell and platelet transfusion			No
Secondary	Incidence of CMV reactivation			No
Secondary	Kinetics of immune reconstitution			No
Secondary	Incidence of paroxysmal nocturnal hemoglobinuria (PNH) clone (lymphoid or myeloid) development			No
Secondary	Incidence of clonal evolution (i.e., karyotypic abnormalities or secondary myelodysplasia/leukemia)			No