Reduced Toxicity Fludarabine, Cyclophosphamide Plus Thymoglobulin Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia
Reduced Toxicity Fludarabine (Flu) + Cyclophosphamide (CPM) + Rabbit Antithymocyte Globulin (rATG) Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia (SAA)
Sponsors
Source
The Korean Society of Pediatric Hematology Oncology
Oversight Info
Has Dmc
Yes
Brief Summary
Anti-thymocyte globulin (ATG) has been used in severe aplastic anemia as a part of the
conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found
to be more effective in preventing graft versus host disease (GVHD) and rejection of organ
transplants. As the fludarabine based conditioning regimens without total body irradiation
have been reported to be promising for transplantation from alternative donors in SAA,
thymoglobulin was added to fludarabine and cyclophosphamide conditioning to reduce GVHD and
to allow good engraftment in unrelated donor transplantation. Our previous phase II study of
fludarabine, cyclophosphamide plus thymoglobulin conditioning resulted in good engraftment
(100%) and survival rate (74%). But grade III/IV toxicities occurred in 25% of patients and
all events were treatment related mortalities. As cyclophosphamide is more toxic agent than
fludarabine, we plan a new phase II study re; 'reduced toxicity fludarabine, cyclophosphamide
plus thymoglobulin conditioning regimen for unrelated donor transplantation in severe
aplastic anemia' by reducing dosage of cyclophosphamide and increasing dosage of fludarabine.
Overall Status
Unknown status
Start Date
2008-11-01
Completion Date
2012-10-01
Primary Completion Date
2012-10-01
Phase
Phase 2
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
To evaluate engraftment potential of reduced toxicity fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia. |
From Nov. 2008 to Oct. 2012 |
Secondary Outcome
Measure |
Time Frame |
|
To evaluate toxicities of reduced toxicity fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for UBMT/PBSCT in SAA. |
From Nov. 2008 to Oct. 2012 |
|
To evaluate overall and EFS rate after UBMT/PBSCT. |
From Nov. 2008 to Oct. 2012 |
|
To evaluate GVHD and immunologic recovery after UBMT/PBSCT. |
From Nov. 2008 to Oct. 2012 |
Enrollment
33
Condition
Intervention
Intervention Type
Drug
Intervention Name
Description
cyclophosphamide (60 mg/kg once daily i.v. on days -8, -7)
fludarabine (40 mg/m2 once daily i.v. on days -6, -5, -4, -3, -2)
thymoglobulin (2.5 mg/kg once daily i.v. on days -4, -3, -2)
Arm Group Label
Fludarabine
Eligibility
Criteria
Inclusion Criteria:
1. Diagnosis of severe aplastic anemia defined by any two or three peripheral blood
criteria and either marrow criterion.
- Peripheral blood
1. Neutrophils < 0.5 x 109/l
2. Platelets < 20 x 109/l
3. Corrected reticulocytes < 1%
- Bone marrow
1. Severe hypocellularity (< 25%)
2. Moderate hypocellularity (25-30%) with hematopoietic cells representing <
30% of residual cells
2. No prior hematopoietic stem cell transplantation.
3. Age: no limits.
4. Performance status: ECOG 0-2.
5. Patients must be free of significant functional deficits in major organs, but the
following eligibility criteria may be modified in individual cases:
- Heart: a shortening fraction > 30% and ejection fraction > 45%.
- Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper
- Kidney: creatinine <2 × normal or a creatinine clearance (GFR) > 60
ml/min/1.73m2.
6. Patients must lack any active viral infections or active fungal infection.
7. Appropriate donor is available: Matched in 6/6 of A, B, DR loci.
8. Patients (or one of parents if patients age < 19) should sign informed consent.
Exclusion Criteria:
1. Pregnant or nursing women.
2. Malignant or nonmalignant illness that is uncontrolled or whose control may be
jeopardized by complications of study therapy.
3. Psychiatric disorder that would preclude compliance.
4. Congenital aplastic anemia including Fanconi anemia.
5. Manipulated bone marrow.
Gender
All
Minimum Age
1 Year
Maximum Age
21 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Hyo seop Ahn, M.D, Ph. D |
Principal Investigator |
The Korean Society of Pediatric Hematology Oncology |
Overall Contact
Location
Facility |
Status |
Contact |
|
Seoul National University Hospital Seoul 110-744 Korea, Republic of |
Recruiting |
Location Countries
Country
Korea, Republic of
Verification Date
2012-03-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Name Title
The Korean Society of Hematology
Organization
The Korean Society of Pediatric of Hematology Oncology
Has Expanded Access
No
Condition Browse
Number Of Arms
1
Intervention Browse
Mesh Term
Cyclophosphamide
Fludarabine phosphate
Thymoglobulin
Antilymphocyte Serum
Fludarabine
Vidarabine
Arm Group
Arm Group Label
Fludarabine
Arm Group Type
Experimental
Firstreceived Results Date
N/A
Overall Contact Backup
Firstreceived Results Disposition Date
N/A
Study Design Info
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
April 15, 2009
Study First Submitted Qc
April 15, 2009
Study First Posted
April 16, 2009
Last Update Submitted
March 23, 2012
Last Update Submitted Qc
March 23, 2012
Last Update Posted
March 26, 2012
Last Known Status
Recruiting
ClinicalTrials.gov processed this data on August 28, 2018
Conditions
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conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.