Clinical trial NCT00167206: Stem Cell Transplantation for Fanconi Anemia
Official title: A Study of Thymic Shielding in Recipients of Total Body Irradiation, Cyclophosphamide, and Fludarabine Followed by Alternate Donor Hematopoietic Stem Cell Transplantation in Patients With Fanconi Anemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Fanconi Anemia
Keywords: Stem Cell Transplant
Thymic Shielding
Total Body Irradiation
Chemotherapy
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2005-09-14
Enrollment: 16
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Patients Who Exhibited Hematopoietic Recovery and Engraftment
timeFrame: Day 42 after hematopoietic cell transplant
Secondary outcomes:
measure: Number of Patients Who Exhibited Secondary Graft Failure
timeFrame: Day 100 after hematopoietic cell transplant
measure: Number of Patients With Acute Graft Versus-Host Disease (aGVHD)
timeFrame: Day 100 after hematopoietic cell transplant
measure: Number of Patients With Chronic Graft Versus-Host Disease (GVHD)
timeFrame: 1 year after hematopoietic cell transplant
measure: Number of Patients Who Exhibited Regimen-related Toxicity (RRT)
timeFrame: 1 year after hematopoietic cell transplant
measure: Immune Reconstitution - Mean Value (1 Year)
timeFrame: 1 year post-transplant.
measure: Immune Reconstitution - Mean Value (2 Years)
timeFrame: at 2 years after transplant
measure: Number of Patients Alive at 1 Year
timeFrame: 1 year after transplant
measure: Number of Patients Alive at 2 Years
timeFrame: 2 years after transplant
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Margaret MacMillan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: MacMillan ML, DeFor TE, Young JA, Dusenbery KE, Blazar BR, Slungaard A, Zierhut H, Weisdorf DJ, Wagner JE. Alternative donor hematopoietic cell transplantation for Fanconi anemia. Blood. 2015 Jun 11;125(24):3798-804. doi: 10.1182/blood-2015-02-626002. Epub 2015 Mar 30.