Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
MT2017-17:T Cell Receptor Alpha/Beta T Cell Depleted Hematopoietic Cell Transplantation in Patients With Inherited Bone Marrow Failure (BMF) Disorders
2 other identifiers
interventional
48
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Nov 2018
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 25, 2018
CompletedFirst Posted
Study publicly available on registry
July 9, 2018
CompletedStudy Start
First participant enrolled
November 13, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 5, 2029
January 30, 2026
January 1, 2026
8.1 years
May 25, 2018
January 29, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Grade II-IV acute graft versus host disease (GVHD)
incidence of grade II-IV acute graft versus host disease (GVHD)
Day 100
Secondary Outcomes (8)
Neutrophil engraftment
Day 42
Platelet engraftment
Day 42
Acute graft versus host disease (aGVHD)
Day 100
Chronic graft versus host disease (cGVHD)
1 Year after transplant
Regimen related toxicity
30 Days after transplant
- +3 more secondary outcomes
Study Arms (5)
Treatment Plan 1: TBI 300 , CY, FLU, MP, Rituximab in patients with Fanconi Anemia
EXPERIMENTALGiven 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
Treatment Plan 2: CY, FLU, MP, Rituximab in patients with Fanconi Anemia
EXPERIMENTALGiven to: • An HLA-identical sibling donor recipients with single or multi- lineage hematopoietic failure
Treatment Plan 3: BU, Cy, FLU, MP and Rituximab in patients with Fanconi Anemia
EXPERIMENTALGiven 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
Treatment Plan 4: CY, FLU, and alemtuzumab
EXPERIMENTALgiven 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.
Treatment Plan 5: CY, FLU, melphalan (MEL), and alemtuzumab.
EXPERIMENTALgiven 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
300 cGy with thymic shielding on day -6
10 mg/kg IV daily on days -5, -4, -3, and -2
35 mg/m2 IV daily on days -5, -4, -3, and -2
1 mg/kg IV q12h on days -5, -4, -3, -2, and -1
T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation on day 0
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)
5 mg/kg IV daily on days -5, -4, -3, and -2
200 mg/m2 IV once on day -1
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 0.2 mg/kg is given IV over 2 hours daily for 5 days (total dose 1 mg/kg)
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.
Eligibility Criteria
You may qualify if:
- 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:
- +6 more criteria
You may not qualify if:
- 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
- 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
- /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
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Margaret MacMillan, MD, Msc, FRCPC
Masonic Cancer Center, University of Minnesota
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 25, 2018
First Posted
July 9, 2018
Study Start
November 13, 2018
Primary Completion (Estimated)
January 1, 2027
Study Completion (Estimated)
January 5, 2029
Last Updated
January 30, 2026
Record last verified: 2026-01