A Study of Cyclophosphamide, Fludarabine, and Antithymocyte Globulin Followed by Matched Sibling Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia
N/A
59 Years
Both
Fanconi Anemia
Trial Information
A Study of Cyclophosphamide, Fludarabine, and Antithymocyte Globulin Followed by Matched Sibling Donor Hematopoietic Cell Transplantation in Patients With Fanconi Anemia
OBJECTIVES:
Primary
- To determine the probability of engraftment in patients with Fanconi anemia treated
with cyclophosphamide, fludarabine phosphate, and antithymocyte globulin followed by
HLA-genotypically identical sibling donor hematopoietic stem cell transplantation that
is T-cell depleted.
Secondary
- To evaluate the incidence of acute graft-versus-host disease (GVHD) and chronic GVHD in
patients treated with this regimen.
- To evaluate the incidence of regimen-related toxicity in these patients.
- To evaluate the 1-year survival of patients treated with this regimen.
- To evaluate the incidence of late secondary malignancies (e.g., squamous cell carcinoma
of the head and neck or cervix) in patients treated with this regimen.
OUTLINE:
- Preparative cytoreductive therapy: Patients receive cyclophosphamide IV over 2 hours on
days -6 to -3 and fludarabine phosphate IV over 30 minutes and anti-thymocyte globulin
IV over 4-6 hours on days -6 to -2.
- T-cell depleted donor hematopoietic stem cell transplantation: Patients undergo T-cell
depleted donor bone marrow or umbilical cord blood stem cell transplantation on day 0.
Patients also receive filgrastim (G-CSF) IV beginning on day 1 and continuing until
blood counts recover.
- Graft-versus-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours or
orally every 8-12 hours beginning on day -3 and continuing until day 100, followed by a
taper. Patients will receive Mycophenolate Mofetil (MMF) therapy beginning on day -3
through day +30 or for 7 days after engraftment, whichever day is later, if no acute
GVHD. Engraftment is defined as 1st day of 3 consecutive days of absolute neutrophil
count [ANC] > 0.5 x 10^9/L.
After completion of study therapy, patients are followed periodically.
Inclusion Criteria:
- Patients must be <60 years of age with a diagnosis of Fanconi Anemia (FA).
- Patients must have an HLA-A, B, DRB1 identical sibling donor. Patients and donors
will be typed for HLA-A and B using serological or molecular techniques and for DRB1
using high resolution molecular typing.
- Patients with FA must have moderately severe aplastic anemia (AA), early
myelodysplastic syndrome (MDS) with no excess blasts with or without chromosomal
abnormalities.
- In patients <18 years of age, moderately severe aplastic anemia is defined as
having at least one of the following:
- platelet count <40 x 10^9/L
- absolute neutrophil count (ANC) <10 x 10^8/L
- Hgb <9 g/dL
- In patients 18-60 years of age, moderately severe aplastic anemia is defined as
having at least one of the following:
- platelet count <20 x 10^9/L
- absolute neutrophil count ANC <5 x 10^8/L
- Hgb <8 g/dL
- Early myelodysplastic syndrome, with multilineage dysplasia with < 5% blasts,
with or without chromosomal anomalies.
- Adequate major organ function including:
- Cardiac: ejection fraction >45%
- Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites)
- Karnofsky performance status >70% or Lansky >50%
- Women of child bearing age must be using adequate birth control and have a negative
pregnancy test.
Exclusion Criteria:
- Active bacterial infection within one week of hematopoietic cell transplant (HCT)
- Active fungal infection at time of HCT.
- Late MDS with greater than 5% blasts in bone marrow.
- Acute myelogenous leukemia (AML) or history of AML
- Malignant solid tumor (e.g. squamous cell carcinoma of the head/neck/cervix) within 2
years of HCT.
- Pregnant or lactating female.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Graft failure
Outcome Description:
graft failure = absolute neutrophil count (ANC) <5 x 10^8/L and an acellular bone marrow aspirate/biopsy
Outcome Time Frame:
From Day 1 to event
Safety Issue:
Yes
Principal Investigator
Margaret L. MacMillan, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Masonic Cancer Center, University of Minnesota
Authority:
United States: Food and Drug Administration
Study ID:
MT2000-09
NCT ID:
NCT00630253
Start Date:
February 2000
Completion Date:
August 2014
Related Keywords:
- Fanconi Anemia
- Fanconi anemia
- Anemia
- Fanconi Anemia
- Fanconi Syndrome
Name | Location |
|---|---|
| Masonic Cancer Center, University of Minnesota | Minneapolis, Minnesota 55455 |
