T Cell Receptor α/β TCD HCT in Patients With Fanconi Anemia
Fanconi Anemia, Severe Aplastic Anemia, Myelodysplastic Syndromes
About this trial
This is an interventional treatment trial for Fanconi Anemia
Eligibility Criteria
Patient Selection:
Inclusion Criteria:
- Diagnosis of Fanconi anemia
- Less than 65 years of age
- Karnofsky performance status of ≥ 70% or, for children < 16 years of age, Lansky Play Score ≥ 50
Presence of at least one of the following risk factors:
Severe aplastic anemia (SAA) defined as: Aplastic anemia is defined as having at least one of the following when not receiving growth factors or transfusions:
- platelet count <20 x 109/L
- absolute neutrophil count of <5 x 108/L
- hemoglobin <8 g/dL
- Myelodysplastic syndrome (MDS) or acute leukemia
- High risk genotype
Adequate organ function defined as:
- Bilirubin, AST or ALT, ALP <5 x normal, Cardiac: left ventricle ejection fraction (LEFV) ≥45% by ECHO
- Pulmonary: DLCO, FEV1, FVC ≥ 40% predicted, and absence of O2 requirements. For children that are not able to cooperate with PFTs, a pulse oximetry with exercise should be attempted. If neither test can be obtained it should be clearly stated in the physician's note.
- Identification of a suitable donor for peripheral blood cells per match criteria found in Section 5.
- Females of childbearing potential and males with partners of child-bearing potential must agree to use of contraception for the duration of treatment and 4 months after the transplant
- Able to provide written voluntary consent prior to the performance of any research related tests or procedures with parental/guardian consent for minor (and assent as appropriate)
Exclusion Criteria:
- Pregnant or breastfeeding as the treatment used in this study are Pregnancy Category D. Females of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days of study registration
- Active, uncontrolled infection within 1 week prior to starting study therapy
- Malignant solid tumor cancer within previous 2 years
Donor Selection (Inclusion Criteria): meets one of the following match criteria:
- an HLA-A, B, DRB1 matched sibling donor (matched sibling)
- an HLA-A, B, DRB1 matched related donor (other than sibling)
- a related donor mismatched at 1 HLA-A, B, C and DRB1 antigen
- 7-8/8 HLA-A,B,C,DRB1 allele matched unrelated donor per current institutional guidelines Patients and donors are typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing. If a donor has been selected on the basis of HLA-A, B, C and DRB1 typing as above, preference will be made for donors matched at the HLA-C locus.
- Body weight of at least 40 kilograms and at least 12 years of age
- Willing and able to undergo mobilized peripheral blood apheresis
- In general good health as determined by the medical provider
Adequate organ function defined as:
- Hematologic: hemoglobin, WBC, platelet within 10% of upper and lower limit of normal range of test (gender based for hemoglobin)
- Hepatic: ALT < 2 x upper limit of normal
- Renal: serum creatinine < 1.8 mg/dl
- Performance of a donor infectious disease screen panel including CMV Antibody, Hepatitis B Surface Antigen, Hepatitis B Core Antibody, Hepatitis C Antibody, HIV 1/2 Antibody, HTLVA 1/2 Antibody, Treponema, and Trypanosoma Cruzi (T. Cruzi) plus HBV, HCV, WNV, HIV by nucleic acid testing (NAT); and screening for evidence of and risks factors for infection with Zika virus, or per current standard institutional donor screen - must be negative for HIV and active hepatitis B
- Not pregnant - females of childbearing potential must have a negative pregnancy test within 7 days of mobilization start
- Voluntary written consent (parent/guardian and minor assent, if < 18 years) prior to the performance of any research related procedure
Sites / Locations
- Masonic Cancer Center at University of MinnesotaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Treatment Plan 1: TBI 300 with Thymic Shielding, CY, FLU, MP
Treatment Plan 2: CY, FLU and MP
Treatment Plan 3: BU, Cy, FLU, MP and Rituximab
Given to: Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type OR Patients with an HLA- identical sibling donor recipient and MDS or acute leukemia
Given to: • HLA-identical sibling donor recipients with aplastic anemia
Given to: Patients with an unrelated donor or HLA mismatched related donor, regardless of disease type who cannot tolerate TBI Patients with an HLA- identical sibling donor recipient and MDS or acute leukemia who cannot tolerate TBI Per treating physician preference