Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders

January 29, 2026 updated by: Masonic Cancer Center, University of Minnesota

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

48

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Margaret MacMillan, MD, Msc, FRCPC
  • Phone Number: 612-626-2961
  • Email: macmi002@umn.edu

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • Masonic Cancer Center at University of Minnesota
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Cyclophosphamide (CY) (Plan 1)
10 mg/kg IV daily on days -5, -4, -3, and -2
Other Names:
  • CY
Drug: Fludarabine (FLU)
35 mg/m2 IV daily on days -5, -4, -3, and -2
Other Names:
  • FLU
Drug: Alemtuzumab
Alemtuzumab 0.2 mg/kg is given IV over 2 hours daily for 5 days (total dose 1 mg/kg)
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
Drug: Total Body Irradiation (TBI) (Plan 1)
300 cGy with thymic shielding on day -6
Other Names:
  • TBI
Drug: Cyclophosphamide (CY) (Plan 1)
10 mg/kg IV daily on days -5, -4, -3, and -2
Other Names:
  • CY
Drug: Fludarabine (FLU)
35 mg/m2 IV daily on days -5, -4, -3, and -2
Other Names:
  • FLU
Drug: Methylprednisolone (MP)
1 mg/kg IV q12h on days -5, -4, -3, -2, and -1
Other Names:
  • MP
Device: Donor mobilized PBSC infusion
T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation on day 0
Other Names:
  • PBSC
Drug: Rituximab
200 mg/m2 IV once on day -1
Drug: 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)
Drug: Rituximab
Rituximab will be given once on treatment plans 1-3 on day -1.
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
Drug: Fludarabine (FLU)
35 mg/m2 IV daily on days -5, -4, -3, and -2
Other Names:
  • FLU
Drug: Methylprednisolone (MP)
1 mg/kg IV q12h on days -5, -4, -3, -2, and -1
Other Names:
  • MP
Device: Donor mobilized PBSC infusion
T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation on day 0
Other Names:
  • PBSC
Drug: Rituximab
200 mg/m2 IV once on day -1
Drug: Cyclophosphamide (CY) (Plan 2)
5 mg/kg IV daily on days -5, -4, -3, and -2
Other Names:
  • CY
Drug: 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)
Drug: Rituximab
Rituximab will be given once on treatment plans 1-3 on day -1.
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
Drug: Cyclophosphamide (CY) (Plan 1)
10 mg/kg IV daily on days -5, -4, -3, and -2
Other Names:
  • CY
Drug: Fludarabine (FLU)
35 mg/m2 IV daily on days -5, -4, -3, and -2
Other Names:
  • FLU
Drug: Methylprednisolone (MP)
1 mg/kg IV q12h on days -5, -4, -3, -2, and -1
Other Names:
  • MP
Drug: Rituximab
200 mg/m2 IV once on day -1
Drug: 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.
Other Names:
  • BU
Drug: Rituximab
Rituximab will be given once on treatment plans 1-3 on day -1.
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.
Drug: Cyclophosphamide (CY) (Plan 1)
10 mg/kg IV daily on days -5, -4, -3, and -2
Other Names:
  • CY
Drug: Fludarabine (FLU)
35 mg/m2 IV daily on days -5, -4, -3, and -2
Other Names:
  • FLU
Drug: Alemtuzumab
Alemtuzumab 0.2 mg/kg is given IV over 2 hours daily for 5 days (total dose 1 mg/kg)
Drug: 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.
Other Names:
  • MEL

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Grade II-IV acute graft versus host disease (GVHD)
Time Frame: Day 100
incidence of grade II-IV acute graft versus host disease (GVHD)
Day 100

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neutrophil engraftment
Time Frame: Day 42
Rate of neutrophil engraftment (defined as the first of three consecutive days after HCT that the patient's absolute neutrophil counts is ≥ 0.5x109 per liter)
Day 42
Platelet engraftment
Time Frame: Day 42
Time to platelet engraftment (First of three consecutive days after HCT that the patient's platelet count ≥ 20x10^9 per liter)
Day 42
Acute graft versus host disease (aGVHD)
Time Frame: Day 100
Incidence of grade III-IV acute graft versus host disease
Day 100
Chronic graft versus host disease (cGVHD)
Time Frame: 1 Year after transplant
Incidence of chronic graft versus host disease after transplant
1 Year after transplant
Regimen related toxicity
Time Frame: 30 Days after transplant
Incidence of regimen related toxicity based on CTCAE v5
30 Days after transplant
Bacterial, viral and fungal infections
Time Frame: 1 Year after transplant
Incidence of bacterial, viral and fungal infections
1 Year after transplant
Opportunistic infections
Time Frame: 100 Days after transplant
Incidence of opportunistic infections
100 Days after transplant
Overall survival (OS)
Time Frame: 1 Year after transplant
Incidence of overall survival
1 Year after transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Masonic Cancer Center, University of Minnesota

Investigators

  • Principal Investigator: Margaret MacMillan, MD, Msc, FRCPC, Masonic Cancer Center, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 13, 2018

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

January 5, 2029

Study Registration Dates

First Submitted

May 25, 2018

First Submitted That Met QC Criteria

July 6, 2018

First Posted (Actual)

July 9, 2018

Study Record Updates

Last Update Posted (Actual)

January 30, 2026

Last Update Submitted That Met QC Criteria

January 29, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016LS161
  • MT2017-17 (Other Identifier: Masonic Cancer Center, University of Minnesota)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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