T Cell Receptor α/β TCD HCT in Patients With Fanconi Anemia

• Status: Recruiting
• Trial end date: 2029-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase II trial of T cell receptor alpha/beta depletion (α/β TCD) hematopoietic cell transplantation (HCT) transplantation in patients with Fanconi anemia (FA) to eliminate the need for routine graft-versus-host disease (GVHD) immune suppression leading to earlier immune recovery and potentially a reduction in the risk of severe infections after transplantation.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Masonic Cancer Center, University of Minnesota
• Treatments: Busulfan; Cyclophosphamide; Fludarabine; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Rituximab

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