Fludarabine-based Conditioning for Severe Aplastic Anemia (BMT CTN 0301)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Blood and Marrow Transplant Clinical Trials Network
Information provided by (Responsible Party):
Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT00326417
First received: May 12, 2006
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

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 Medical College of Wisconsin:

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: 94
Study Start Date: January 2006
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms 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

  Eligibility

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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Hide Study Locations
Locations
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Mattel Children's Hospital at UCLA
Los Angeles, California, United States, 90095
Stanford Hospital and Clinics
Stanford, California, United States, 94305
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33624
United States, Georgia
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30322
BMT Program at Northside Hospital
Atlanta, Georgia, United States, 30342
United States, Massachusetts
DFCI/Brigham & Women's Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Memorial Sloan-Kettering Cancer Center
New York City, New York, United States, 10021
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239-3098
United States, Texas
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
University of Texas, MD Anderson CRC
Houston, Texas, United States, 77030
Texas Transplant Institute
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Commonwealth University, MCV Hospital
Richmond, Virginia, United States, 23298
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Medical College of Wisconsin
Blood and Marrow Transplant Clinical Trials Network
Investigators
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: Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT00326417     History of Changes
Obsolete Identifiers: NCT00335608
Other Study ID Numbers: 383, U01HL069294, BMT CTN 0301, 5 U01 HL69294-05
Study First Received: May 12, 2006
Last Updated: June 2, 2014
Health Authority: United States: Federal Government

Keywords provided by Medical College of Wisconsin:
Severe Aplastic Anemia

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

ClinicalTrials.gov processed this record on October 20, 2014