Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
NCT ID: NCT03579875
Last Updated: 2026-01-30
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
48 participants
INTERVENTIONAL
2018-11-13
2029-01-05
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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
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)
Rituximab
200 mg/m2 IV once on day -1
Rituximab
Rituximab will be given once on treatment plans 1-3 on day -1.
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
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
Rituximab
Rituximab will be given once on treatment plans 1-3 on day -1.
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
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
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.
Rituximab
Rituximab will be given once on treatment plans 1-3 on day -1.
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.
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
Alemtuzumab
Alemtuzumab 0.2 mg/kg is given IV over 2 hours daily for 5 days (total dose 1 mg/kg)
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.
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
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.
Interventions
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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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
Exclusion Criteria
* Active, uncontrolled infection within 1 week prior to starting study therapy
* Malignant solid tumor cancer within previous 2 years
65 Years
ALL
No
Sponsors
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Masonic Cancer Center, University of Minnesota
OTHER
Responsible Party
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Principal Investigators
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Margaret MacMillan, MD, Msc, FRCPC
Role: PRINCIPAL_INVESTIGATOR
Masonic Cancer Center, University of Minnesota
Locations
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Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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MT2017-17
Identifier Type: OTHER
Identifier Source: secondary_id
2016LS161
Identifier Type: -
Identifier Source: org_study_id
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