MT2017-17:T Cell Receptor Alpha/Beta T Cell Depleted Hematopoietic Cell Transplantation in Patients With Inherited Bone Marrow Failure (BMF) Disorders

Description

This is a phase II trial of T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation in patients with inherited bone marrow failure (BMF) disorders 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.

Trial Eligibility

Patient Selection: Inclusion Criteria: For FA patients: * Diagnosis of Fanconi anemia * Age \<65 years of age * Has one of the following risk factors: * Severe aplastic anemia (SAA) * Myelodysplastic syndrome (MDS) * High risk genotype * Immunodeficiency associated with history of recurrent infections * Karnofsky performance status ≥ 70% if ≥ 16 years of age or Lansky play score ≥ 50% for patients \<16 years of age * Adequate pulmonary, cardiac and liver function * Voluntary written consent (minor assent if appropriate) prior to the performance of any study related procedures not part of standard medical care For TBD patients: • Diagnosis of TBD * Age \<70 years of age * Has one of the following risk factors: * Severe aplastic anemia (SAA) * Myelodysplastic syndrome (MDS) * Karnofsky performance status ≥ 70% if ≥ 16 years of age or Lansky play score ≥ 50% for patients \<16 years of age * Adequate pulmonary, cardiac and liver function * Voluntary written consent (minor assent if appropriate) prior to the performance of any study related procedures not part of standard medical care 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

Study Info

Interventions

Locations Recruiting

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