Stem Cell Transplantation for Fanconi Anemia

Phase 1

Terminated

Conditions: Fanconi Anemia

Interventions: Procedure: Hematopoietic Stem Cell Transplant
Procedure: Thymic Shielding During Radiation
Procedure: Total Body Irradiation
Drug: Cyclophosphamide, Fludarabine

Registration Number: NCT00167206

Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief Summary: The purpose of this study is to determine whether thymic shielding during total body irradiation can be given and whether it will reduce the risk of infections in Fanconi Anemia patients undergoing alternate donor (not a matched sibling) stem cell transplants.

Detailed Description: All subjects will be given the same treatment regimen of total body irradiation (TBI), Fludarabine, Cyclophosphamide, and anti-thymocyte globulin (ATG), followed by an alternate donor stem cell transplant. Since this treatment regimen has been given before, without thymic shielding, we will compare the outcomes of these patients with the historical data from subjects who did not receive thymic shielding.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 16

Inclusion Criteria

Patients must be less than (<) 18 years of age with a diagnosis of Fanconi anemia.
Patients must have an HLA-A, B, DRB1 identical unrelated donor or less than or equal to (≤)1 antigen mismatched related (non-HLA-matched sibling) or <1 antigen mismatched unrelated UCB 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 aplastic anemia (AA), myelodysplastic syndrome without excess blasts, or high risk genotype as defined below.
- Aplastic anemia is defined as having at least one of the following when not receiving growth factors or transfusions
- Platelet count <20 x 10^9/L
- ANC <5 x 10^8/L
- Hgb <8 g/dL
- Myelodysplastic syndrome with multilineage dysplasia with or without chromosomal anomalies
- High risk genotype (e.g. IVS-4 or exon 14 FANCC mutations, or BRCA1 or 2 mutations)
Adequate major organ function including
- Cardiac: ejection fraction greater than (>)45%
- Hepatic: bilirubin, AST/ALT, ALP <2 x normal
- Karnofsky performance status >70% or Lansky performance status >50%
Women of child-bearing age must be using adequate birth control and have a negative pregnancy test

Exclusion Criteria

Available HLA-genotypically identical related donor
History of gram negative sepsis or systemic fungal infection (proven or suspected based on radiographic studies)
Refractory anemia with excess blasts, or leukemia
Active central nervous system (CNS) leukemia at time of hematopoietic cell transplant (HCT)
History of squamous cell carcinoma of the head/neck/cervix within 2 years of HCT
Pregnant or lactating female
Prior radiation therapy preventing use of total body irradiation (TBI) 450 centigray (cGy)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HSCT Patients	Cyclophosphamide, Fludarabine	Patients who received total body irradiation (450 cGy \[centigray\]) with thymic shielding prior to chemotherapy regimen and Hematopoietic Stem Cell Transplant (HSCT)
HSCT Patients	Total Body Irradiation	Patients who received total body irradiation (450 cGy \[centigray\]) with thymic shielding prior to chemotherapy regimen and Hematopoietic Stem Cell Transplant (HSCT)
HSCT Patients	Hematopoietic Stem Cell Transplant	Patients who received total body irradiation (450 cGy \[centigray\]) with thymic shielding prior to chemotherapy regimen and Hematopoietic Stem Cell Transplant (HSCT)
HSCT Patients	Thymic Shielding During Radiation	Patients who received total body irradiation (450 cGy \[centigray\]) with thymic shielding prior to chemotherapy regimen and Hematopoietic Stem Cell Transplant (HSCT)

Primary Outcome Measures

Name	Time	Method
Number of Patients Who Exhibited Hematopoietic Recovery and Engraftment	Day 42 after hematopoietic cell transplant	Calculated from Day 1 of hematopoietic cell transplant to Day 42 post-transplant. Hematopoietic recovery and engraftment is defined as the first of three consecutive days the patient's absolute neutrophil count is greater than or equal to 0.5X10\^9/Liter.

Secondary Outcome Measures

Name	Time	Method
Number of Patients Who Exhibited Secondary Graft Failure	Day 100 after hematopoietic cell transplant	Calculated from Day 1 of hematopoietic cell transplant to Day 100 after transplant. A complication after Bone Marrow Transplant in which the transplanted stem cells do not grow in the recipient's bone marrow and thus do not produce new blood cells.
Number of Patients With Acute Graft Versus-Host Disease (aGVHD)	Day 100 after hematopoietic cell transplant	Calculated from Day 1 of hematopoietic cell transplant to Day 100 after transplant. GVHD is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack.
Number of Patients With Chronic Graft Versus-Host Disease (GVHD)	1 year after hematopoietic cell transplant	Calculated from Day 1 of hematopoietic cell transplant to 1 year after transplant. GVHD is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack.
Number of Patients Who Exhibited Regimen-related Toxicity (RRT)	1 year after hematopoietic cell transplant	Calculated from Day 1 of hematopoietic cell transplant to 1 year after transplant. Regimen-related toxicity involves harmful effects in an organism through exposure to the treatment given.
Immune Reconstitution - Mean Value (1 Year)	1 year post-transplant.	Calculated mean value of patient CD4 values collected at intervals from Day 30 through 1 year post-transplant.
Immune Reconstitution - Mean Value (2 Years)	at 2 years after transplant	Calculated mean value of patient CD4 values collected at intervals from Day 30 through 2 years post-transplant.
Number of Patients Alive at 1 Year	1 year after transplant	Calculated from Day 1 of hematopoietic cell transplant to 1 year post-transplant.
Number of Patients Alive at 2 Years	2 years after transplant	Calculated from Day 1 of hematopoietic cell transplant to 2 years post-transplant.