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

Primary Purpose

Nonmalignant Neoplasm

Status
Unknown status
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
alemtuzumab
cyclosporine
Sponsored by
Federico II University
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nonmalignant Neoplasm focused on measuring aplastic anemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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)

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)

Sites / Locations

  • Federico II University Medical SchoolRecruiting

Outcomes

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)

Full Information

First Posted
May 7, 2009
Last Updated
August 9, 2013
Sponsor
Federico II University
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1. Study Identification

Unique Protocol Identification Number
NCT00895739
Brief Title
Alemtuzumab and Low-Dose Cyclosporine in Treating Patients With Severe Aplastic Anemia or Acquired Marrow Failure
Official Title
Alemtuzumab and Low-Dose Cyclosporine-A as Alternative Immunosuppressive Treatment for Severe Aplastic Anemia (SAA) and Single-Lineage Aplastic Patients
Study Type
Interventional

2. Study Status

Record Verification Date
May 2009
Overall Recruitment Status
Unknown status
Study Start Date
June 2006 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Federico II University

4. Oversight

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonmalignant Neoplasm
Keywords
aplastic anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruno Rotoli, MD
Organizational Affiliation
Federico II University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Federico II University Medical School
City
Naples
ZIP/Postal Code
80131
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bruno Rotoli, MD
Phone
39-081-746-2068
Email
rotoli@unina.it

12. IPD Sharing Statement

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

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