Fanconi Anemia
Conditions
Keywords
Stem Cell Transplant, Thymic Shielding, Total Body Irradiation, Chemotherapy
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.
Interventions
PROCEDUREHematopoietic Stem Cell Transplant
Bone marrow failure may be treated by giving patients stem cells that come from someone else. This is called a stem-cell transplant. As part of the transplant process, patients receive high doses of chemotherapy and/or radiation to treat their underlying disease. As one of its effects, this treatment also kills the healthy stem cells that are already in the marrow. The transplant provides new stem cells for the patient from a healthy donor; that replace the bone marrow and allow the blood counts to recover.
PROCEDUREThymic Shielding During Radiation
protecting the thymus during total body radiation (450 cGy administered)
PROCEDURETotal Body Irradiation
Six days before the stem cells are given (day -6), subjects will receive total body irradiation with thymic shielding. Thymic shielding is done by placing a piece of lead on the chest during the irradiation treatment so that the irradiation beams do not go to the thymus.
Day -5 through Day -2, subjects will receive a chemotherapy regimen of Fludarabine, Cyclophosphamide via central line
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 18 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intent-To-Treat All patients with Fanconi anemia who received thymic shielding during total body irradiation (450 cGy). | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Intent-To-Treat |
|---|---|
| Age, Categorical <=18 years | 16 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 9.8 years STANDARD_DEVIATION 4.5 |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Number of Patients Who Exhibited Hematopoietic Recovery and Engraftment
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.
Time frame: Day 42 after hematopoietic cell transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intent-To-Treat | Number of Patients Who Exhibited Hematopoietic Recovery and Engraftment | 15 Participants |
Secondary
Immune Reconstitution - Mean Value (1 Year)
Calculated mean value of patient CD4 values collected at intervals from Day 30 through 1 year post-transplant.
Time frame: 1 year post-transplant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intent-To-Treat | Immune Reconstitution - Mean Value (1 Year) | 860 Number of CD4 cells per microliter | Standard Deviation 870 |
Secondary
Immune Reconstitution - Mean Value (2 Years)
Calculated mean value of patient CD4 values collected at intervals from Day 30 through 2 years post-transplant.
Time frame: at 2 years after transplant
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intent-To-Treat | Immune Reconstitution - Mean Value (2 Years) | 1100 Number of CD4 cells per microliter | Standard Deviation 510 |
Secondary
Number of Patients Alive at 1 Year
Calculated from Day 1 of hematopoietic cell transplant to 1 year post-transplant.
Time frame: 1 year after transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intent-To-Treat | Number of Patients Alive at 1 Year | 11 Participants |
Secondary
Number of Patients Alive at 2 Years
Calculated from Day 1 of hematopoietic cell transplant to 2 years post-transplant.
Time frame: 2 years after transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intent-To-Treat | Number of Patients Alive at 2 Years | 10 Participants |
Secondary
Number of Patients Who Exhibited Regimen-related Toxicity (RRT)
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.
Time frame: 1 year after hematopoietic cell transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intent-To-Treat | Number of Patients Who Exhibited Regimen-related Toxicity (RRT) | 5 Participants |
Secondary
Number of Patients Who Exhibited Secondary Graft Failure
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.
Time frame: Day 100 after hematopoietic cell transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intent-To-Treat | Number of Patients Who Exhibited Secondary Graft Failure | 1 Participants |
Secondary
Number of Patients With Acute Graft Versus-Host Disease (aGVHD)
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.
Time frame: Day 100 after hematopoietic cell transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intent-To-Treat | Number of Patients With Acute Graft Versus-Host Disease (aGVHD) | 8 Participants |
Secondary
Number of Patients With Chronic Graft Versus-Host Disease (GVHD)
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.
Time frame: 1 year after hematopoietic cell transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intent-To-Treat | Number of Patients With Chronic Graft Versus-Host Disease (GVHD) | 2 Participants |