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Reduced Toxicity Fludarabine (Flu) + Cyclophosphamide (CPM) + Rabbit Antithymocyte Globulin (rATG) Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia (SAA)

Primary Purpose

Aplastic Anemia

Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Cyclophosphamide, Fludarabine, Thymoglobulin
Sponsored by
The Korean Society of Pediatric Hematology Oncology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aplastic Anemia

Eligibility Criteria

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

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.

Sites / Locations

  • Seoul National University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fludarabine

Arm Description

Outcomes

Primary Outcome Measures

To evaluate engraftment potential of reduced toxicity fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia.

Secondary Outcome Measures

To evaluate toxicities of reduced toxicity fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for UBMT/PBSCT in SAA.
To evaluate overall and EFS rate after UBMT/PBSCT.
To evaluate GVHD and immunologic recovery after UBMT/PBSCT.

Full Information

First Posted
April 15, 2009
Last Updated
March 23, 2012
Sponsor
The Korean Society of Pediatric Hematology Oncology
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1. Study Identification

Unique Protocol Identification Number
NCT00882323
Brief Title
Reduced Toxicity Fludarabine (Flu) + Cyclophosphamide (CPM) + Rabbit Antithymocyte Globulin (rATG) Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia (SAA)
Official Title
Reduced Toxicity Fludarabine, Cyclophosphamide Plus Thymoglobulin Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia
Study Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Unknown status
Study Start Date
November 2008 (undefined)
Primary Completion Date
October 2012 (Anticipated)
Study Completion Date
October 2012 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
The Korean Society of Pediatric Hematology Oncology

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aplastic Anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Enrollment
33 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fludarabine
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide, Fludarabine, Thymoglobulin
Intervention 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)
Primary Outcome Measure Information:
Title
To evaluate engraftment potential of reduced toxicity fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia.
Time Frame
From Nov. 2008 to Oct. 2012
Secondary Outcome Measure Information:
Title
To evaluate toxicities of reduced toxicity fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for UBMT/PBSCT in SAA.
Time Frame
From Nov. 2008 to Oct. 2012
Title
To evaluate overall and EFS rate after UBMT/PBSCT.
Time Frame
From Nov. 2008 to Oct. 2012
Title
To evaluate GVHD and immunologic recovery after UBMT/PBSCT.
Time Frame
From Nov. 2008 to Oct. 2012

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of severe aplastic anemia defined by any two or three peripheral blood criteria and either marrow criterion. Peripheral blood Neutrophils < 0.5 x 109/l Platelets < 20 x 109/l Corrected reticulocytes < 1% Bone marrow Severe hypocellularity (< 25%) Moderate hypocellularity (25-30%) with hematopoietic cells representing < 30% of residual cells No prior hematopoietic stem cell transplantation. Age: no limits. Performance status: ECOG 0-2. 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. Patients must lack any active viral infections or active fungal infection. Appropriate donor is available: Matched in 6/6 of A, B, DR loci. Patients (or one of parents if patients age < 19) should sign informed consent. Exclusion Criteria: Pregnant or nursing women. Malignant or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy. Psychiatric disorder that would preclude compliance. Congenital aplastic anemia including Fanconi anemia. Manipulated bone marrow.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hyoung Jin Kang, M.D, Ph.D
Phone
82 2 2072 3304
Email
kanghj@snu.ac.kr
First Name & Middle Initial & Last Name or Official Title & Degree
Ji Won Lee, M.D
Phone
82 2 2072 0177
Email
agnesjw@hanmil.net
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hyo seop Ahn, M.D, Ph. D
Organizational Affiliation
The Korean Society of Pediatric Hematology Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hyo Seop Ahn, M.D, Ph.D
Phone
82 2 2072 3625
Email
hsahn@snu.ac.kr

12. IPD Sharing Statement

Citations:
PubMed Identifier
20685256
Citation
Kang HJ, Shin HY, Park JE, Chung NG, Cho B, Kim HK, Kim SY, Lee YH, Lim YT, Yoo KH, Sung KW, Koo HH, Im HJ, Seo JJ, Park SK, Ahn HS; Korean Society of Pediatric Hematology-Oncology. Successful engraftment with fludarabine, cyclophosphamide, and thymoglobulin conditioning regimen in unrelated transplantation for severe aplastic anemia: A phase II prospective multicenter study. Biol Blood Marrow Transplant. 2010 Nov;16(11):1582-8. doi: 10.1016/j.bbmt.2010.05.010. Epub 2010 May 26.
Results Reference
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Reduced Toxicity Fludarabine (Flu) + Cyclophosphamide (CPM) + Rabbit Antithymocyte Globulin (rATG) Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia (SAA)

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