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

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University of Minnesota (UMN)

Status and phase

Enrolling
Phase 2

Conditions

Fanconi Anemia
Myelodysplastic Syndromes
Severe Aplastic Anemia

Treatments

Drug: Fludarabine (FLU)
Drug: Rituximab
Device: Donor mobilized PBSC infusion
Drug: Total Body Irradiation (TBI) (Plan 1)
Drug: Cyclophosphamide (CY) (Plan 1)
Drug: Methylprednisolone (MP)
Drug: G-CSF
Drug: Busulfan
Drug: Cyclophosphamide (CY) (Plan 2)

Study type

Interventional

Funder types

Other

Identifiers

NCT03579875
MT2017-17 (Other Identifier)
2016LS161

Details and patient eligibility

About

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.

Enrollment

48 estimated patients

Sex

All

Ages

Under 65 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

Trial design

48 participants in 3 patient groups

Treatment Plan 1: TBI 300 with Thymic Shielding, CY, FLU, MP
Experimental group
Description:
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
Treatment:
Drug: G-CSF
Drug: Methylprednisolone (MP)
Drug: Cyclophosphamide (CY) (Plan 1)
Drug: Total Body Irradiation (TBI) (Plan 1)
Device: Donor mobilized PBSC infusion
Drug: Rituximab
Drug: Fludarabine (FLU)
Treatment Plan 2: CY, FLU and MP
Experimental group
Description:
Given to: • HLA-identical sibling donor recipients with aplastic anemia
Treatment:
Drug: Cyclophosphamide (CY) (Plan 2)
Drug: G-CSF
Drug: Methylprednisolone (MP)
Device: Donor mobilized PBSC infusion
Drug: Rituximab
Drug: Fludarabine (FLU)
Treatment Plan 3: BU, Cy, FLU, MP and Rituximab
Experimental group
Description:
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
Treatment:
Drug: Busulfan
Drug: Methylprednisolone (MP)
Drug: Cyclophosphamide (CY) (Plan 1)
Drug: Rituximab
Drug: Fludarabine (FLU)

Trial contacts and locations

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Central trial contact

Lisa Burke, RN

Data sourced from clinicaltrials.gov

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