Recruiting
Phase 2

Alpha/Beta TCD HCT

Sponsor:

Masonic Cancer Center, University of Minnesota

Code:

NCT03579875

Conditions

Fanconi Anemia

Severe Aplastic Anemia

Myelodysplastic Syndromes

T Cell Receptor Alpha/Beta Depletion

Telomere Biology Disorder

Eligibility Criteria

Sex: All

Age: 0 - 65

Healthy Volunteers: Not accepted

Interventions

Total Body Irradiation (TBI) (Plan 1)

Cyclophosphamide (CY) (Plan 1)

Fludarabine (FLU)

Methylprednisolone (MP)

Donor mobilized PBSC infusion

Study Details

Brief summary:

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.

Conditions

Fanconi Anemia

Severe Aplastic Anemia

Myelodysplastic Syndromes

T Cell Receptor Alpha/Beta Depletion

Telomere Biology Disorder

Study ID

NCT03579875

Start date

Nov 13, 2018

Status verified date

Jan, 2026

Completion date

Jan 5, 2029

Anticipated

Primary completion date

Jan 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 65

Healthy Volunteers: Not accepted

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 features
  • 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 features
  • 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 Design

Enrollment

48 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment Plan 1: TBI 300 , CY, FLU, MP, Rituximab in patients with Fanconi Anemia

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 myelodysplastic features, MDS, or acute leukemia

experimental: Treatment Plan 2: CY, FLU, MP, Rituximab in patients with Fanconi Anemia

Given to:

• An HLA-identical sibling donor recipients with single or multi- lineage hematopoietic failure

experimental: Treatment Plan 3: BU, Cy, FLU, MP and Rituximab in patients with Fanconi 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 myelodysplastic features, MDS, or acute leukemia who cannot tolerate TBI
  • Biallelic mutations in FANCD1/BRCA2 who cannot receive TBI
  • Per treating physician preference

experimental: Treatment Plan 4: CY, FLU, and alemtuzumab

given to TBD patients with:

  • Bone marrow failure AND
  • Any donor type including haploidentical (4/8) to 8/8-HLA matched related donor, or 7-8/8 HLA-matched unrelated donor Based on historical numbers, it is expected approximately 3 patients would be treated per year. Statistical outcomes will be descriptive.

experimental: Treatment Plan 5: CY, FLU, melphalan (MEL), and alemtuzumab.

given to TBD patients with:

  • Early myelodysplastic features (with or without cytogenetic abnormalities) AND
  • Any donor type including haploidentical (4/8) to 8/8-HLA matched related donor, or 7-8/8 HLA-matched unrelated donor Based on historical numbers, it is expected approximately 2 patients would be treated per year. Statistical outcomes will be descriptive.

Interventions

Total Body Irradiation (TBI) (Plan 1)

300 cGy with thymic shielding on day -6

Cyclophosphamide (CY) (Plan 1)

10 mg/kg IV daily on days -5, -4, -3, and -2

Fludarabine (FLU)

35 mg/m2 IV daily on days -5, -4, -3, and -2

Methylprednisolone (MP)

1 mg/kg IV q12h on days -5, -4, -3, -2, and -1

Donor mobilized PBSC infusion

T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation on day 0

G-CSF

Initiate G-CSF 5mcg/kg per day IV on day +1 (continue until ANC >2.5 x 10\^9/L for 3 consecutive days or single day ANC >3000 Arm 1 and Arm 3)

Cyclophosphamide (CY) (Plan 2)

5 mg/kg IV daily on days -5, -4, -3, and -2

Rituximab

200 mg/m2 IV once on day -1

Busulfan

Busulfan 0.6 mg/kg if > 4 years old and/or >12 kg (0.8 mg/kg IV if ≤ 4 years old and/or ≤ 12 kg) is given IV over 2 hours every 12 hours for 2 days.

Alemtuzumab

Alemtuzumab 0.2 mg/kg is given IV over 2 hours daily for 5 days (total dose 1 mg/kg)

Melphalan

If available, MEL dosing will be model-based using Bayesian methodology. If Bayesian methodology is unavailable, MEL dosing will be weight-based: MEL 70 mg/m2 for patients ≥10 kg (2.35 mg/kg for patients <10 kg\^) IV for one dose over 30 minutes.

Rituximab

Rituximab will be given once on treatment plans 1-3 on day -1.

Primary outcome measure

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

Central Contacts and Locations

Central contacts

Margaret MacMillan, MD, Msc, FRCPC

612-626-2961macmi002@umn.edu

Locations

Masonic Cancer Center at University of Minnesota

Recruiting

Minneapolis, Minnesota, United States, 55455

Contacts

Lisa Burke, RN

612-273-8482lburke3@Fairview.org

More Information

Sponsor

Masonic Cancer Center, University of Minnesota

Last update posted

Jan 30, 2026

Last verified

Jan, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Masonic Cancer Center, University of Minnesota on 2026-01-30.