Text Size

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

This study is currently recruiting participants.
Verified March 2012 by The Korean Society of Pediatric Hematology Oncology
Sponsor:
Information provided by:
The Korean Society of Pediatric Hematology Oncology
ClinicalTrials.gov Identifier:
NCT00882323
First received: April 15, 2009
Last updated: March 23, 2012
Last verified: March 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Aplastic Anemia
 Drug: Cyclophosphamide, Fludarabine, Thymoglobulin
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Reduced Toxicity Fludarabine, Cyclophosphamide Plus Thymoglobulin Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by The Korean Society of Pediatric Hematology Oncology:

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. [ Time Frame: From Nov. 2008 to Oct. 2012 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • To evaluate overall and EFS rate after UBMT/PBSCT. [ Time Frame: From Nov. 2008 to Oct. 2012 ] [ Designated as safety issue: No ]
  • To evaluate GVHD and immunologic recovery after UBMT/PBSCT. [ Time Frame: From Nov. 2008 to Oct. 2012 ] [ Designated as safety issue: No ]

Estimated Enrollment: 33
Study Start Date: November 2008
Estimated Study Completion Date: October 2012
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fludarabine Drug: Cyclophosphamide, Fludarabine, Thymoglobulin

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)

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00882323

Contacts
Contact: Hyoung Jin Kang, M.D, Ph.D 82 2 2072 3304 kanghj@snu.ac.kr
Contact: Ji Won Lee, M.D 82 2 2072 0177 agnesjw@hanmil.net

Locations
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Hyo Seop Ahn, M.D, Ph.D     82 2 2072 3625     hsahn@snu.ac.kr    
Sponsors and Collaborators
The Korean Society of Pediatric Hematology Oncology
Investigators
Principal Investigator: Hyo seop Ahn, M.D, Ph. D The Korean Society of Pediatric Hematology Oncology
  More Information

No publications provided

Responsible Party: The Korean Society of Hematology, The Korean Society of Pediatric of Hematology Oncology
ClinicalTrials.gov Identifier: NCT00882323     History of Changes
Other Study ID Numbers: KSPHO-SCT 0802
Study First Received: April 15, 2009
Last Updated: March 23, 2012
Health Authority: Korea: Food and Drug Administration

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Antilymphocyte Serum
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
 Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on May 16, 2013