T Cell Receptor a/ß TCD HCT in Patients With Fanconi Anemia

• Register: ClinicalTrials.gov
• Last refreshed on: 13 November 2023
• Main ID: NCT03579875
• Date of registration: 25/05/2018
• Prospective Registration: Yes
• Primary sponsor: Masonic Cancer Center, University of Minnesota
• Public title: T Cell Receptor a/ß TCD HCT in Patients With Fanconi Anemia
• Scientific title: T Cell Receptor Alpha/Beta T Cell Depleted (a/ß TCD) Hematopoietic Cell Transplantation in Patients With Fanconi Anemia (FA)
• Date of first enrolment: November 13, 2018
• Target sample size: 48
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03579875
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Lisa Burke, RN

• Name: Margaret MacMillan, MD, Msc, FRCPC
• Affiliation: Masonic Cancer Center, University of Minnesota

• Name: Lisa Burke, RN

Key inclusion & 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



Age minimum: N/A
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Fanconi Anemia

Severe Aplastic Anemia

Myelodysplastic Syndromes

Intervention(s)

Drug: Fludarabine (FLU)

Drug: Cyclophosphamide (CY) (Plan 1)

Device: Donor mobilized PBSC infusion

Drug: Busulfan

Drug: Methylprednisolone (MP)

Drug: Total Body Irradiation (TBI) (Plan 1)

Drug: Rituximab

Drug: Cyclophosphamide (CY) (Plan 2)

Drug: G-CSF

Primary Outcome(s)

Grade II-IV acute graft versus host disease (GVHD) [Time Frame: Day 100]

Secondary Outcome(s)

Overall survival (OS) [Time Frame: 1 Year after transplant]

Regimen related toxicity [Time Frame: 30 Days after transplant]

Chronic graft versus host disease (cGVHD) [Time Frame: 1 Year after transplant]

Platelet engraftment [Time Frame: Day 42]

Acute graft versus host disease (aGVHD) [Time Frame: Day 100]

Neutrophil engraftment [Time Frame: Day 42]

Opportunistic infections [Time Frame: 100 Days after transplant]

Bacterial, viral and fungal infections [Time Frame: 1 Year after transplant]

Secondary ID(s)

MT2017-17

2016LS161

Source(s) of Monetary Support

Please refer to primary and secondary sponsors