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: January 27, 2015
Last verified: January 2015
  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: Fludarabine
Drug: Cyclophosphamide 150mg
Drug: Cyclophosphamide 100mg
Drug: Cyclophosphamide 50mg
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:
  • Disease-free survival (DFS) [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    Graft Failure, Regimen-related Toxicity (RRT), and Early Death. Graft Failure is defined by lack of neutrophil engraftment (ANC less than 0.5 x 10^9/L for 3 consecutive days on different days). Regimen-related Toxicity (RRT) is scored according to the Bearman scale.


Secondary Outcome Measures:
  • Secondary Graft Failure [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
    Secondary Graft Failure is 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.

  • Acute GVHD [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
    Grades 2-4 and 3-4 - graded according to the BMT CTN Manual of Procedures (MOP)

  • Chronic GVHD [ Time Frame: Day 730 ] [ Designated as safety issue: No ]
    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.

  • 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: Cyclophosphamide 150mg
Fludarabine plus 150 mg/kg Cyclophosphamide (total dose)
Drug: Fludarabine
Doses of 30 mg/m2 IV will be given for no less than 30 minutes daily for 4 days (Days -5 to -2)
Other Name: Fludara
Drug: Cyclophosphamide 150mg
A total dose of 150 mg/kg will be given as 50 mg/kg per day for 3 days (Days -4, -3, -2)
Other Name: Cytoxan®
Experimental: Cyclophosphamide 100mg
Fludarabine plus 100 mg/kg Cyclophosphamide (total dose)
Drug: Fludarabine
Doses of 30 mg/m2 IV will be given for no less than 30 minutes daily for 4 days (Days -5 to -2)
Other Name: Fludara
Drug: Cyclophosphamide 100mg
A total dose of 100 mg/kg will be given as 50 mg/kg per day for 2 days (Days -3, -2)
Other Name: Cytoxan®
Experimental: Cyclophosphamide 50mg
Fludarabine plus 50 mg/kg Cyclophosphamide (total dose)
Drug: Fludarabine
Doses of 30 mg/m2 IV will be given for no less than 30 minutes daily for 4 days (Days -5 to -2)
Other Name: Fludara
Drug: Cyclophosphamide 50mg
A total dose of 50 mg/kg will be given once at 50 mg/kg per day on Day -2
Other Name: Cytoxan®
Experimental: Fludarabine
Fludarabine only (no Cyclophosphamide administered)
Drug: Fludarabine
Doses of 30 mg/m2 IV will be given for no less than 30 minutes daily for 4 days (Days -5 to -2)
Other Name: Fludara

  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), alanine transaminase (ALT) and aspartate transaminase (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: Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and carbon monoxide diffusing capacity (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 myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) on marrow examination
  • Diagnosis of other "congenital" aplastic anemias such as: Diamond-Blackfan; Shwachman-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

  Show 22 Study Locations
Sponsors and Collaborators
Medical College of Wisconsin
Blood and Marrow Transplant Clinical Trials Network
Investigators
Study Director: Mary Horowitz, MD Center for International Blood and Marrow Transplant Research
  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: BMTCTN0301, U01HL069294, BMT CTN 0301, 5U01HL069294-05
Study First Received: May 12, 2006
Last Updated: January 27, 2015
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
Fludarabine phosphate
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
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 June 01, 2015