Fludarabine-Based Conditioning for Allogeneic Marrow Transplantation in Aplastic Anemia

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT00474747
• Date of registration: 16/05/2007
• Prospective Registration: No
• Primary sponsor: M.D. Anderson Cancer Center
• Public title: Fludarabine-Based Conditioning for Allogeneic Marrow Transplantation in Aplastic Anemia
• Scientific title: Fludarabine-Based Conditioning for Allogeneic Marrow Transplantation From HLA-Compatible Unrelated Donors in Severe Aplastic Anemia
• Date of first enrolment: February 7, 2006
• Target sample size: 5
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00474747
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Paolo Anderlini, MD
• Affiliation: M.D. Anderson Cancer Center

Key inclusion & exclusion 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
forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and
diffusing capacity of lung for carbon monoxide (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 myelodysplastic syndrome (MDS) or
acute myeloblastic leukemia (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 graft-versus-host disease
(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.



Age minimum: N/A
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Aplastic Anemia

Intervention(s)

Procedure: Bone Marrow Transplant

Drug: Fludarabine

Drug: Antithymocyte Globulin

Drug: Cyclophosphamide

Radiation: Total Body Irradiation (TBI)

Primary Outcome(s)

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]

Secondary Outcome(s)

Two-year post-transplant survival [Time Frame: 2 Years post transplant]

Secondary ID(s)

NCI-2010-00908

2005-0513

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)

National Heart, Lung, and Blood Institute (NHLBI)