A Pilot Trial of Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine
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Fanconi Anemia
Trial Information
A Pilot Trial of Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using Total Body Irradiation, Cyclophosphamide and Fludarabine
Patients with this disease are born with it and have a fragility of the genes (chromosomes)
in all the cells of the body. The fragility of the chromosomes puts patients with FA at high
risk for certain cancers. Patients with FA are especially at risk of having diseases of the
blood and marrow systems. These include (1) aplastic anemia, a disease where there is a
failure of the bone marrow to make blood cells and (2) myelodysplastic syndrome which is
represented by a clone of cells of the marrow that becomes "malignant" and stops making
adequate numbers of blood cells (it is also called preleukemia.) The progression of the
myelodysplastic syndrome will lead to (3) acute leukemia.
If you have Fanconi anemia and suffer from aplastic anemia, myelodysplastic syndrome, or
leukemia standard treatment with medications or chemotherapy alone is not likely to cure
these problems.
An allogeneic blood or bone marrow (hematopoietic stem cell) transplant can be done to
provide you with marrow or blood stem cells from a healthy donor that can develop a normal
blood forming system. An allogeneic stem cell transplant can cure the problems of the marrow
and blood system. It cannot cure the chromosome fragility of the whole body. When allogeneic
stem cell transplants have been done for the treatment of FA using stem cells from donors
other than matched siblings, they have been associated with a high risk of rejection of the
transplant and of a complication called graft-versus-host disease.
In order for the stem cells to grow and to kill leukemia cells, patients must receive
chemotherapy and radiation therapy. This preparation is called cytoreduction. For patients
with Fanconi anemia, the standard preparation for stem cell transplantation has been the use
of total body irradiation (at a lower dose because of the high risk of side-effects) and a
chemotherapy agent called cyclophosphamide (or Cytoxan) also at lower dose. While this has
worked well with transplants from matched siblings, it was not enough in transplants from
unrelated or cord blood donors and led to a high risk of rejection. In the last few years a
medication called fludarabine was used successfully in transplants to give more
immunosuppression and kill T-cells. Fludarabine allowed transplants to be done with low
risks of rejection, and probably as importantly little risks of added side-effects. The
addition of antithymocyte globulin to TBI, cyclophosphamide and fludarabine has made the
chances of rejection very low.
Inclusion Criteria:
Diagnosis:
- Research participants must be have a diagnosis of Fanconi anemia (confirmed by
mitomycin or diepoxybutane [DEB] chromosomal breakage testing).
Hematologic Diagnosis and Status:
- Research participants must have one of the following hematologic diagnoses:
- Severe Aplastic Anemia (SAA)/Severe Isolated Single lineage Cytopenia
- Myelodysplastic Syndrome(MDS)
- Acute leukemia.
HLA-compatible Unrelated volunteer donors:
- Research participants who do not have a related HLA-matched donor but have an
unrelated donor who is either matched at all A, B and DRB1 loci or who is mismatched
at 1/6 loci (A, B, or DRB1) as tested by DNA analysis, will be eligible for entry on
this protocol.
HLA-mismatched Related donors:
- Research participants who do not have a related or unrelated HLA-compatible donor
must have a healthy family member who is at least HLA-haplotype identical to the
recipient. First degree related donors must have a normal DEB test.
- The donor must be healthy and willing and able (1) to receive a 5 day course of G-CSF
and undergo 2 daily leukaphereses, or (2) to undergo general anesthesia and bone
marrow donation. In order to undergo a Tcell depletion, a donor should be able to
have a volume of 15 ml/Kg of the research participant's body weight harvested safely.
HLA-compatible Cord Blood Units:
- Research participants who do not have a related HLA-matched donor but have an
unrelated placental cord blood unit which matched at all A, B and DRB1 loci or who is
mismatched at 1/6 or 2/6 loci (A, B, or DRB1) as tested by DNA analysis, will be
eligible for entry on this protocol.
- Research participants may be of either gender or any ethnic background.
- Research participants must have a Karnofsky adult, or Lansky pediatric performance
scale status > 70%.
- At the time of referral for transplantation, research participants must be in good
clinical condition without co-existing medical problems that would significantly
increase the risk of the transplant procedure. Research participants must be free of
infections at the time of transplant. Research participants must have a life
expectancy that is greater than 8 weeks.
- Research participants must have adequate physical function measured by cardiac,
Hepatic, Renal, Pulmonary.
- Research participants must be available for follow-up evaluations at 30, 60, 180 days
post BMT and yearly for 5 years.
Exclusion Criteria:
- Active CNS leukemic involvement
- Female research participants who are pregnant or breast-feeding
- Active viral, bacterial or fungal infection
- Research participant seropositive for HIV-I/II; HTLV -I/II
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Incidence & quality of engraftment & hematopoietic reconstitution/Early transplant-related severe morbidity & mortality/Incidence & severity of acute & chronic GvHD/Quality of immune reconstitution following transplantation/Overall survival rate.
Outcome Time Frame:
8 years
Safety Issue:
Yes
Principal Investigator
Farid Boulad, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
01-062
NCT ID:
NCT00595127
Start Date:
June 2001
Completion Date:
May 2013
Related Keywords:
- Fanconi Anemia
- Fanconi
- Anemia
- Stem Cell
- Transplant
- Anemia
- Fanconi Anemia
- Fanconi Syndrome
Name | Location |
|---|---|
| Memorial Sloan Kettering Cancer Center | New York, New York 10021 |
