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

Primary Purpose

Severe Aplastic Anemia

Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Cyclophosphamide, Fludarabine, Rabbit ATG
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Aplastic Anemia focused on measuring Anemia, Severe, Aplastic, Reduced-Intensity, Allogeneic, Stem, Cell, Transplantation

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Reduced-Intensity Preparative Regimen for Allogeneic SCT

    Arm 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.

    Outcomes

    Primary Outcome Measures

    Engraftment rate

    Secondary Outcome Measures

    Relapse
    Development of Graft vs. Host Disease
    Evaluation of the occurrence of secondary malignancies
    Overall survival
    Evaluation of treatment feasibility
    Evaluation of toxicities

    Full Information

    First Posted
    April 21, 2010
    Last Updated
    March 23, 2012
    Sponsor
    City of Hope Medical Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01129323
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2012
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    This study did not accrue any subjects and due to this will be closed.
    Study Start Date
    November 2009 (undefined)
    Primary Completion Date
    September 2011 (Actual)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    City of Hope Medical Center

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Severe Aplastic Anemia
    Keywords
    Anemia, Severe, Aplastic, Reduced-Intensity, Allogeneic, Stem, Cell, Transplantation

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Reduced-Intensity Preparative Regimen for Allogeneic SCT
    Arm Type
    Experimental
    Arm 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.
    Intervention Type
    Drug
    Intervention Name(s)
    Cyclophosphamide, Fludarabine, Rabbit ATG
    Intervention Description
    Fludarabine 30mg/m2/dose IV and cyclophosphamide 10mg/kg/dose IV are given once per day from day -5 to -2. rATG 1.5 mg/kg/dose IV is given from day -4 to -1.
    Primary Outcome Measure Information:
    Title
    Engraftment rate
    Time Frame
    Day 42 after allogeneic transplant
    Secondary Outcome Measure Information:
    Title
    Relapse
    Time Frame
    Days 180, 365 and yearly post transplant
    Title
    Development of Graft vs. Host Disease
    Time Frame
    Days 180, 365 and yearly post transplant
    Title
    Evaluation of the occurrence of secondary malignancies
    Time Frame
    Days 180, 365 and yearly post transplant
    Title
    Overall survival
    Time Frame
    Days 180, 365 and yearly post transplant
    Title
    Evaluation of treatment feasibility
    Time Frame
    Days 180, 365 and yearly post transplant
    Title
    Evaluation of toxicities
    Time Frame
    Days 180, 365 and yearly post transplant

    10. Eligibility

    Sex
    All
    Maximum Age & Unit of Time
    21 Years
    Accepts Healthy Volunteers
    No
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Anna Pawlowska, MD
    Organizational Affiliation
    City of Hope Medical Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

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