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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00895739
First received: May 7, 2009
Last updated: August 9, 2013
Last verified: May 2009
  Purpose

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 Intervention Phase
Nonmalignant Neoplasm
Biological: alemtuzumab
Drug: cyclosporine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety, as defined by occurrence of adverse effects [ Designated as safety issue: Yes ]
  • Overall survival [ Designated as safety issue: No ]
  • Hematologic response (partial and complete response, including time to response) [ Designated as safety issue: No ]
  • Failure-free survival (failure is defined as no response, chronic treatment-maintained response, or relapse) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of adverse effects after treatment [ Designated as safety issue: Yes ]
  • Long-term safety of alemtuzumab treatment [ Designated as safety issue: Yes ]
  • Time to achieve a complete hematological response [ Designated as safety issue: No ]
  • Proportion of patients maintaining hematological response free of any treatment [ Designated as safety issue: No ]
  • Incidence of relapse in responding patients [ Designated as safety issue: No ]
  • Incidence of severe infections [ Designated as safety issue: No ]
  • Requirement for IV antibiotics and antifungal therapy [ Designated as safety issue: No ]
  • Requirement for red cell and platelet transfusion [ Designated as safety issue: No ]
  • Incidence of CMV reactivation [ Designated as safety issue: No ]
  • Kinetics of immune reconstitution [ Designated as safety issue: No ]
  • Incidence of paroxysmal nocturnal hemoglobinuria (PNH) clone (lymphoid or myeloid) development [ Designated as safety issue: No ]
  • Incidence of clonal evolution (i.e., karyotypic abnormalities or secondary myelodysplasia/leukemia) [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: June 2006
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00895739

Locations
Italy
Federico II University Medical School Recruiting
Naples, Italy, 80131
Contact: Bruno Rotoli, MD    39-081-746-2068    rotoli@unina.it   
Sponsors and Collaborators
Federico II University
Investigators
Principal Investigator: Bruno Rotoli, MD Federico II University
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00895739     History of Changes
Other Study ID Numbers: UNMS-ALESAA, CDR0000639649, EU-20927, EUDRACT-2008-001151-22
Study First Received: May 7, 2009
Last Updated: August 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
aplastic anemia

Additional relevant MeSH terms:
Anemia, Aplastic
Anemia
Hematologic Diseases
Bone Marrow Diseases
Cyclosporins
Cyclosporine
Alemtuzumab
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on October 01, 2014