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Withdrawn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
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
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
NCT ID
NCT01129323
First Posted
April 21, 2010
Last Updated
March 23, 2012
Sponsor
City of Hope Medical Center
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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