Fludarabine-Based Conditioning for Allogeneic Marrow Transplantation in Aplastic Anemia

Fludarabine-Based Conditioning for Allogeneic Marrow Transplantation in Aplastic Anemia
This study is currently recruiting participants.
Verified April 2012 by M.D. Anderson Cancer Center

First Received on May 16, 2007.  
Last Updated on April 9, 2012  
History of Changes
Sponsor: M.D. Anderson Cancer Center
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Information provided by (Responsible Party): M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00474747

The goal of this clinical research study is to find out the best dose of cyclophosphamide that can be given with fludarabine, antithymocyte globulin (ATG), and low-dose total body irradiation (TBI) to patients before a bone marrow transplant to decrease the risks related to the transplant while not decreasing the effectiveness of the transplant from an unrelated donor.

Condition Intervention Phase
Aplastic Anemia Drug: Antithymocyte Globulin
Drug: Cyclophosphamide
Drug: Fludarabine
Radiation: Total Body Irradiation (TBI)
Procedure: Bone Marrow Transplant
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Fludarabine-Based Conditioning for Allogeneic Marrow Transplantation From HLA-Compatible Unrelated Donors in Severe Aplastic Anemia

Resource links provided by NLM:

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

  • Optimal dose level of cyclophosphamide based on assessments of graft failure, toxicity and early death [ Time Frame: During 100 days of follow-up post-transplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

  • Two-year post-transplant survival [ Time Frame: 2 Years post transplant ] [ Designated as safety issue: No ]

Estimated Enrollment: 81
Study Start Date: February 2006
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)


Assigned Interventions
Experimental: Fludarabine + Antithymocyte Globulin + Cyclophosphamide Drug: Antithymocyte Globulin

3 mg/kg IV over no less than four (and preferably six) hours daily x 3 days
Other Names:
  • Thymoglobulin
  • ATG

Drug: Cyclophosphamide

Starting maximum dose 50 mg/kg IV x 3 days (de-escalating doses follow).
Other Names:
  • Cytoxan
  • Neosar

Drug: Fludarabine

30 mg/m^2 IV over no less than 30 minutes daily x 4 days
Other Names:
  • Fludarabine Phosphate
  • Fludara

Radiation: Total Body Irradiation (TBI)

TBI: 200 cGy from a linear accelerator at 20 cGy/min on Day -1 (single dose)

Procedure: Bone Marrow Transplant

Infusion of matched unrelated donor marrow on Day 0.
Other Names:
  • BMT
  • Blood And Marrow Transplantation

Show Detailed Description


Ages Eligible for Study:   up to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients up to 65 years of age at time of registration with a diagnosis of severe aplastic anemia (SAA). SAA is defined as follows: – Bone marrow cellularity < 25%, or marrow cellularity < 50% but with < 30% residual hematopoietic cells. Two out of three of the following (in peripheral blood): neutrophils < 0.5 x 10^9/L; platelets < 20 x 10^9/L; reticulocytes < 20 x 10^9/L. SAA diagnostic criteria may be applied to assessment at initial diagnosis or to the follow-up assessments.
  2. Patient must have an available unrelated donor with a 7/8 or 8/8 match for HLA-A, B, C and DRB1 antigen. Typing is by DNA techniques: intermediate resolution for A, B and C, and high resolution for DRB1. HLA-DQ typing is recommended but will not count in the match
  3. Patient and/or legal guardian able to provide signed informed consent.
  4. Matched unrelated donor must consent to provide marrow allograft.
  5. Patients with adequate organ function as measured by: a) cardiac: left ventricular ejection fraction at rest must be > 40% or shortening fraction > 20% b) hepatic: serum total bilirubin < 2x upper limit of normal for age as per local laboratory; ALT and AST < 4x upper limit of normal for age as per local laboratory; c) renal: serum creatinine < 2x upper limit of normal for age (as per local laboratory). d) pulmonary FEV1, FVC and DLCO (corrected for Hb) > 50% predicted. For pts where pulse oxymetry is performed, O2 saturation > 92%
  6. The diagnosis of Fanconi anemia must be excluded in patients younger than 18 years of age by diepoxybutane (DEB) testing on peripheral blood or comparable testing or marrow.

Exclusion Criteria:

  1. Clonal cytogenetic abnormalities associated with MDS or AML on marrow examination.
  2. Diagnosis of other "congenital" aplastic anemias such as: Diamond-Blackfan; Shwachman-Diamond; congenital megakaryocytosis.
  3. Symptomatic or uncontrolled cardiac failure or coronary artery disease.
  4. Karnofsky performance status < 60% or Lansky < 40% for patients < 16 years of old.
  5. Uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms). Patients with fevers despite broad-spectrum antimicrobials but no clinical or hemodynamic evidence of sepsis will be allowed.
  6. Seropositive for the human immunodeficiency virus (HIV).
  7. Pregnancy (positive ß-HCG) or breastfeeding.
  8. Presence of large accumulation of ascites or pleural effusions, which would be a contraindication to the administration of methotrexate for GVHD prophylaxis.
  9. Known severe or life-threatening allergy or intolerance to ATG or cyclosporine/tacrolimus.
  10. Planned administration of alemtuzumab (Campath-1H) or other investigational agents as alternative agent for GVHD prophylaxis.
  11. Concomitant enrollment in a Phase I study.
  12. Positive patient anti-donor lymphocyte crossmatch in HLA-A or B mismatched transplants (test recommended but not mandatory). The definition of match is in Section 2.2.1.
  13. Prior allogeneic marrow or stem cell transplantation.
  14. Patients with prior malignancies except resected basal cell carcinoma or treated carcinoma in-situ. Cancer treated with curative intent < 5 years previously will not be allowed unless approved by the Medical Monitor or Protocol Chair. Cancer treated with curative intent > 5 years previously will be allowed.
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00474747

Contact: Paolo Anderlini, MD 713-792-8750

United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Paolo Anderlini, MD            
Sponsors and Collaborators
M.D. Anderson Cancer Center
Principal Investigator: Paolo Anderlini, MD M.D. Anderson Cancer Center
  More Information

Additional Information:

No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00474747    
History of Changes
Other Study ID Numbers: 2005-0513
Study First Received: May 16, 2007
Last Updated: April 9, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Severe Aplastic Anemia
Total Body Irradiation
Antithymocyte Globulin
Fludarabine Phosphate

Additional relevant MeSH terms:

Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Antilymphocyte Serum
Fludarabine monophosphate
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
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 21, 2012

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