Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Alternate Title

Antithymocyte Globulin Prior to Bone Marrow Transplantation in Treating Patients With Fanconi's Anemia Developing Into Myelodysplastic Syndrome or Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	40 and under	Other	FHCRC-710.01 NCI-V94-0388

Objectives

I.  Determine whether the addition of antithymocyte globulin to a 
marrow-ablation regimen of TBI/CTX reduces acute and delayed 
transplant-related toxicity and improves engraftment rate in patients with 
Fanconi anemia (FA) with myelodysplastic or leukemic transformation undergoing 
allogeneic marrow transplantation.
 

Entry Criteria

Disease Characteristics:

Fanconi anemia (FA) with myelodysplastic or leukemic
transformation that meets all the following criteria:
  Presence of increased chromosome fragility determined by
  diepoxybutane (DEB) testing or at least 3 of the following
  congenital malformations:
     Growth retardation
     Abnormal pigmentation
     Kidney/urinary tract abnormality
     Microphthalmia
     Learning disability
     Thumb/radius abnormality
     Other skeletal abnormality

  Presence of clonal cytogenetic abnormalities, i.e.:
     2 or more cells acquired the same structural abnormality
     2 or more cells acquired the same chromosome (trisomy)
     3 or more cells lost the same chromosome (monosomy)

  Presence of leukemia or of MDS features, including:
     Refractory anemia (RA)
     RA with ringed sideroblasts (RARS)
     RA with excess blasts (RAEB)
     RAEB in transformation (RAEBT)
     Chronic monomyelocytic leukemia (CMML)

History of bone marrow failure not required

Allogeneic marrow donor meeting one of the following criteria
required:
  Genotypically HLA-identical related donor
     If more than 1 eligible donor, preference is given to
     female, nulliparous and untransfused, over 18 years
     old

  Haploidentical related donor matched for HLA-A, -B, and -DRB1

  Haploidentical related donor with 1- or 2-antigen mismatch at
  HLA-A, -B, or -DRB1 loci

  Phenotypically identical unrelated donor matched for HLA-A,
  -B, and -DRB1

  Unrelated donor with a single micro disparity or minor
  mismatch at HLA-A or -B or with a DRB1 minor mismatch (DR
  identical/DRB1 nonidentical)

Donor exclusions:
  DEB-positive test for FA
  Positive lymphocytotoxic crossmatch
  HIV positivity
  Medical or psychological contraindication to donation

Prior/Concurrent Therapy:

Not specified

Patient Characteristics:

Age:
  40 and under

Performance status:
  Not specified

Other:
  No liver, renal, or cardiac disease that would prevent
     compliance with ablation and GVHD regimen
  No disseminated infection that would severely limit survival
     as delineated in the Standard Practice Manual
  No HIV seropositivity

Expected Enrollment

Approximately 2 patients/year in clonal evolution or with myelodysplastic or 
leukemic transformation are expected to be transplanted over 3-5 years.

Outline

Patients with a genotypically or phenotypically identical or 1-antigen 
mismatched related donor or with a phenotypically identical unrelated donor 
are treated on Regimen A; those with a related donor mismatched for more than 
1 HLA antigen or a minor mismatched unrelated donor are treated on Regimen B.  
The following acronyms are used:
  ABM      Allogeneic Bone Marrow
  ATG      Antithymocyte Globulin
  CTX      Cyclophosphamide, NSC-26271
  GVHD     Graft-versus-Host Disease
  TBI      Total-Body Irradiation

Regimen A:  Myeloablative Radiotherapy plus Single-Agent Chemotherapy followed 
by Bone Marrow Transplantation.  TBI (equipment not specified); plus CTX; 
followed by ABM.

Regimen B:  Myeloablative Radiotherapy plus Single-Agent Chemotherapy plus 
Immunosuppression followed by Bone Marrow Transplantation.  TBI; plus CTX; 
plus ATG; followed by ABM.

Trial Contact Information

Trial Lead Organizations

Fred Hutchinson Cancer Research Center

H. Joachim Deeg, MD, Protocol chair		Ph: 206-667-5985 Email: jdeeg@fhcrc.org

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