Fludarabine-Based Conditioning for Allogeneic Marrow Transplantation in Aplastic Anemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00474747
First received: May 16, 2007
Last updated: January 3, 2014
Last verified: January 2014
  Purpose

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: 94
Study Start Date: February 2006
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fludarabine + Antithymocyte Globulin + Cyclophosphamide
Fludarabine 30 mg/m^2 IV over no less than 30 minutes daily x 4 days. Antithymocyte Globulin 3 mg/kg IV over no less than four (and preferably six) hours daily x 3 days. Cyclophosphamide starting maximum dose 50 mg/kg IV x 3 days (de-escalating doses follow). Total Body Irradiation (TBI) 200 cGy from a linear accelerator at 20 cGy/min on Day -1 (single dose). Infusion of matched unrelated donor marrow on Day 0.
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

  Eligibility

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

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

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
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: January 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Severe Aplastic Anemia
Total Body Irradiation
Antithymocyte Globulin
Cyclophosphamide
Cytoxan
Neosar
Fludarabine
Fludara
Fludarabine Phosphate
Thymoglobulin
ATG
TBI
Cyclosporine
Tacrolimus

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Antilymphocyte Serum
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Vidarabine
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
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 15, 2014