Reduced-Intensity Preparative Regimen for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia

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Brief Title

Reduced-Intensity Preparative Regimen for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia

Official Title

Reduced-Intensity Preparative Regimen for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia

Brief Summary

      The purpose of this study is to evaluate the effectiveness of allogeneic transplant after a
      reduced-intensity preparative regimen for patient, to evaluate survival, and to evaluate the
      side effects of this treatment. The patient will be in the study for two years for treatment
      and active monitoring. After treatment and active monitoring are over, the patient's medical
      condition will be followed indefinitely.
    

Detailed Description

      Aplastic Anemia is a blood disorder where bone marrow does not produce enough cells for
      blood. Patients with aplastic anemia have lower counts of all three blood cell types (RBC,
      WBC, and Platelet). Severe cases of aplastic anemia that are untreated can lead to death from
      bleeding and overwhelming infection.

      For patients with Severe Aplastic Anemia (SAA), allogeneic hematopoietic stem cell transplant
      (HSCT) from an HLA-identical sibling is an accepted treatment for restoring normal bone
      marrow function. Preparative regimens for allogeneic HSCT are designed to give the highest
      tolerated doses of chemotherapy, with or without total body irradiation (TBI), in order to
      fully "ablate" or destroy the patient host's bone marrow so that the transplanted cells from
      the HLA-identical sibling can engraft in the patient host.

      While allogeneic HSCT has been proven to be a curative form of therapy for SAA, it is also
      associated with high transplant-related morbidity (side effects) and possible mortality
      (death). One of the toxic side effects from high-dose chemotherapy and TBI are believed to be
      a major contributing factor to "Graft-versus-Host Disease" (GVHD).

      Preliminary studies have shown that a reduced intensity (non-myeloablative) allogeneic HSCT
      may be just as effective in treating SAA. Low-dose chemotherapy is used instead of high-dose
      chemotherapy and TBI. Some smaller studies have indicated that reduced intensity preparative
      regimens using Fludarabine and Cyclophosphamide allowed engraftment in the matched sibling
      donor setting with an acceptable level of toxic side effects in subjects with a variety of
      hematologic cancers. Additional studies that followed showed that a reduced intensity
      preparative regimen that included fludarabine, cyclophosphamide and antithymocyte globulin,
      allowed engraftment of donor stem cells in subjects with SAA with acceptable engraftment
      rates and a decrease in the severity of GVHD.

      This study is designed to evaluate the effectiveness of allogeneic transplant after a
      reduced-intensity preparative regimen, to evaluate survival, and to evaluate the side effects
      including GVHD of this treatment. Patients will be in the study for two years for treatment
      and active monitoring. All patients will be followed until death.
    


Study Type

Interventional


Primary Outcome

Engraftment rate

Secondary Outcome

 Relapse

Condition

Severe Aplastic Anemia

Intervention

Cyclophosphamide, Fludarabine, Rabbit ATG

Study Arms / Comparison Groups

 Reduced-Intensity Preparative Regimen for Allogeneic SCT
Description:  Patient in this arm will receive maximally tolerated (reduced) doses of cytotoxic therapy with the goals of suppressing the immune system, and ablate host hematopoiesis to ensure engraftment of the donor's hematopoietic system.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

0

Start Date

November 2009


Primary Completion Date

September 2011

Eligibility Criteria

        Inclusion Criteria:

          -  21 years old or younger

          -  Male or female recipients must have histopathologically confirmed diagnosis of severe
             aplastic anemia. Diagnostic Criteria for Server Aplastic Anemia will be based on the
             definitions set forth by the international Aplastic Anemia Study Group

          -  At least two of the following:

        Absolute neutrophil count <0.5 x 109/L Platelet count <20 x 109 /L Anemia with corrected
        reticulocyte count <1%

        AND

          -  Bone marrow cellularity <25%, or bone marrow cellularity <50% with fewer than 30%
             hematopoietic cell

          -  Availability of an HLA identical sibling

        Exclusion Criteria:

          -  Active and uncontrolled infection

          -  HIV-1 infection

          -  Pregnancy or breastfeeding.

          -  DLCO <40% predicted

          -  Left Ventricular Ejection Fraction < 40%

          -  Performance scale Karnofsky <=40% or Lansky<=40% for patients <16 years old
      

Gender

All

Ages

N/A - 21 Years

Accepts Healthy Volunteers

No

Contacts

Anna Pawlowska, MD, , 



Administrative Informations


NCT ID

NCT01129323

Organization ID

07081


Responsible Party

Sponsor

Study Sponsor

City of Hope Medical Center


Study Sponsor

Anna Pawlowska, MD, Principal Investigator, City of Hope Medical Center


Verification Date

March 2012