Fludarabine-based Conditioning for Severe Aplastic Anemia

Fludarabine-based Conditioning for Severe Aplastic Anemia (BMT CTN 0301)
This study is currently recruiting participants.
Verified August 2012 by National Heart, Lung, and Blood Institute (NHLBI)

First Received on May 12, 2006.  
Last Updated on August 15, 2012  
History of Changes
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Collaborators: Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
Information provided by (Responsible Party): National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00326417

The purpose of the current study is to continue to optimize conditioning regimens in high-risk patients with severe aplastic anemia transplanted with marrow from HLA-compatible unrelated donors. Specifically, the study will determine whether the addition of fludarabine to the conditioning regimen previously described by Deeg et al. will permit a reduction in the CY dose, to a point where sustained hematopoietic engraftment and survival are maintained (or improved), while the frequency of major regimen-related toxicity (RRT) and early deaths is reduced.

Condition Intervention Phase
Anemia, Aplastic Drug: Cyclophosphamide Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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 (BMT CTN #0301)

Resource links provided by NLM:

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

  • Graft Failure – defined by lack of neutrophil engraftment (ANC less than 0.5 x 10^9/L for 3 consecutive days on different days) [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
  • Regimen-related Toxicity (RRT) – scored according to the Bearman scale [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
  • Early Death [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

  • Secondary Graft Failure – defined by initial neutrophil engraftment followed by subsequent decline in the ANC to less than 0.5 x 10^9/L for three consecutive measurements on different days, unresponsive to growth factor [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
  • Acute GVHD of Grades 2-4 and 3-4 – graded according to the BMT CTN Manual of Procedures [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
  • Chronic GVHD – Chronic GVHD is scored according to the BMT CTN MOP. The first day of chronic GVHD onset will be used to calculate cumulative incidence curves. [ Time Frame: Day 730 ] [ Designated as safety issue: No ]
  • Post-transplant Survival [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 81
Study Start Date: January 2006
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)


Assigned Interventions
Experimental: 1 Cyclophosphamide

150 mg/kg Cyclophosphamide (total dose)
Drug: Cyclophosphamide

total dose 150 mg/kg given as 50 mg/kg per day on Days -4, -3, -2
Experimental: 2 Cyclophosphamide

100 mg/kg Cyclophosphamide (total dose)
Drug: Cyclophosphamide

total dose 100 mg/kg given as 50 mg/kg per day on Days -3, -2
Experimental: 3 Cyclophosphamide

50 mg/kg Cyclophosphamide (total dose)
Drug: Cyclophosphamide

total dose 50 mg/kg given as 50 mg/kg per day on Day -2
Experimental: 4 Cyclophosphamide

0 mg/kg Cyclophosphamide (total dose)
Drug: Cyclophosphamide

total dose 0 mg/kg

Show Detailed Description


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

Inclusion Criteria:

  • Patients up to 65 years of age at time of registration with a diagnosis of SAA; SAA is defined as follows:

    1. Bone marrow cellularity less than 25% or marrow cellularity less than 50% but with less than 30% residual hematopoietic cells
    2. Two out of three of the following (in peripheral blood): neutrophils less than 0.5 x 10^9/L; platelets less than 20 x 10^9/L; reticulocytes less than 20 x 10^9/L
  • 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
  • Patient and/or legal guardian able to provide signed informed consent
  • Matched unrelated donor must consent to provide a marrow allograft
  • Patients with adequate organ function as measured by:

    1. Cardiac: left ventricular ejection fraction at rest must be greater than 40% or shortening fraction greater than 20%
    2. Hepatic: serum bilirubin less than 2x upper limit of normal for age as per local laboratory) (with the exception of isolated hyperbilirubinemia due to Gilbert’s syndrome), ALT and AST less than 4x upper limit of normal for age (as per local laboratory)
    3. Renal: serum creatinine less than 2x upper limit of normal for age (as per local laboratory)
    4. Pulmonary: FEVl, FVC, and DLCO (corrected for Hb) greater than 50% predicted; for patients in which pulse oxymetry is performed, O2 saturation greater than 92%
  • Diagnosis of Fanconi anemia must be excluded in patients younger than 18 years of age by diepoxybutane testing on peripheral blood or comparable testing on marrow.

Exclusion Criteria:

  • Clonal cytogenetic abnormalities associated with MDS or AML on marrow examination
  • Diagnosis of other "congenital" aplastic anemias such as: Diamond-Blackfan; Shwachmann-Diamond; congenital amegakaryocytosis
  • Symptomatic or uncontrolled cardiac failure or coronary artery disease
  • Karnofsky performance status less than 60% or Lansky less than 40% for patients younger than 16 years old
  • Uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms)
  • Seropositive for the human immunodeficiency virus (HIV)
  • Pregnant (positive total HCG) or breastfeeding
  • Presence of large accumulation of ascites or pleural effusions, which would be a contraindication to the administration of methotrexate for GVHD prophylaxis
  • Known severe or life-threatening allergy or intolerance to ATG or cyclosporine/ tacrolimus
  • Planned administration of alemtuzumab (Campath-1H) or other investigational agents as alternative agent for GVHD prophylaxis
  • Concomitant enrollment in a Phase I study
  • Positive patient anti-donor lymphocyte crossmatch in HLA-A or B mismatched transplants; the definition of match is in Section 2.2.1; the crossmatch would only apply to mismatches at HLA-A or B, not DRB1 or HLA-C
  • Prior allogeneic marrow or stem cell transplantation
  • Patients with prior malignancies except resected basal cell carcinoma or treated carcinoma in-situ; cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Medical Monitor or Protocol Chair; cancer treated with curative intent more than 5 years previously will be allowed
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00326417

Contact: Mary Horowitz, MD, MS marymh@mcw.edu

Show 28 Study Locations

Sponsors and Collaborators
Blood and Marrow Transplant Clinical Trials Network
Principal Investigator: Roberta Adams, MD Phoenix Children’s Hospital
Principal Investigator: Neena Kapoor, MD Children’s Hospital Los Angeles
Principal Investigator: Meg O’Donnell, MD City of Hope National Medical Center
Principal Investigator: Theodore Moore, MD Mattel Children’s Hospital at UCLA
Principal Investigator: Sally Arai, MD Stanford Hospital and Clinics
Principal Investigator: John Wingard, MD University of Florida College of Medicine (Shands)
Principal Investigator: John Horan, MD, MPH Children’s Healthcare of Atlanta
Principal Investigator: Leslie Lehmann, MD DFCI/Children’s Hospital of Boston
Principal Investigator: Joseph Antin, MD DFCI/Brigham & Women’s Hospital
Principal Investigator: Carrie Kitko, MD University of Michigan
Principal Investigator: Jakub Tolar, MD, PhD University of Minnesota – Clinical and Translational Science Institute
Principal Investigator: Joel Brochstein, MD Hackensack University Medical Center
Principal Investigator: Hugo Castro-Malaspina, MD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Nelson Chao, MD Duke University
Principal Investigator: Richard Harris, MD Children’s Hospital Medical Center, Cincinnati
Principal Investigator: Amanda Termuhlen, MD Nationwide Children’s Hospital
Principal Investigator: Victor Aquino, MD Children’s Medical Center Dallas
Principal Investigator: Paul Shaughnessy, MD Texas Transplant Institute
Study Chair: Paolo Anderlini, MD University of Texas, MD Anderson CRC
Principal Investigator: John McCarty, MD Virginia Commonwealth University, MCV Hospital
Principal Investigator: Joachim Deeg, MD Fred Hutchinson Cancer Research Center
Principal Investigator: Naynesh Kamani, MD Children’s Research Institute
Principal Investigator: Gretchen Eames, MD Cook Children’s Medical Center
Principal Investigator: Philip McCarthy, MD Roswell Park Cancer Institute
Principal Investigator: Gabrielle Meyers, MD Oregon Health and Science University
Principal Investigator: Stephen Medlin, DO Avera Hematology & Transplant Center
  More Information

Additional Information:

No publications provided

Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00326417    
History of Changes
Obsolete Identifiers: NCT00335608
Other Study ID Numbers: 383, BMT CTN 0301, 5 U01 HL69294-05
Study First Received: May 12, 2006
Last Updated: August 15, 2012
Health Authority: United States: Federal Government

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Severe Aplastic Anemia

Additional relevant MeSH terms:

Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
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

ClinicalTrials.gov processed this record on August 21, 2012

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