Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders

Part of paid clinical trials in Minneapolis, Minnesota.

Sponsor
Masonic Cancer Center, University of Minnesota
Study ID
NCT03579875
Phase
PHASE2
Status
Recruiting
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Conditions

  • Bone Marrow Failure
  • Dyskeratosis Congenita
  • Fanconi Anemia
  • Myelodysplastic Syndromes
  • Severe Aplastic Anemia
  • T Cell Receptor Alpha/Beta Depletion
  • Telomere Biology Disorder
  • Telomere Biology Disorders

Eligibility Criteria

Sex
ALL
Age
N/A - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • Total Body Irradiation (TBI) (Plan 1) — DRUG
    300 cGy with thymic shielding on day -6
  • Cyclophosphamide (CY) (Plan 1) — DRUG
    10 mg/kg IV daily on days -5, -4, -3, and -2
  • Fludarabine (FLU) — DRUG
    35 mg/m2 IV daily on days -5, -4, -3, and -2
  • Methylprednisolone (MP) — DRUG
    1 mg/kg IV q12h on days -5, -4, -3, -2, and -1
  • Donor mobilized PBSC infusion — DEVICE
    T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation on day 0
  • G-CSF — DRUG
    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) — DRUG
    5 mg/kg IV daily on days -5, -4, -3, and -2
  • Rituximab — DRUG
    200 mg/m2 IV once on day -1
  • Busulfan — DRUG
    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 — DRUG
    Alemtuzumab 0.2 mg/kg is given IV over 2 hours daily for 5 days (total dose 1 mg/kg)
  • Melphalan — DRUG
    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 — DRUG
    Rituximab will be given once on treatment plans 1-3 on day -1.

Study Details

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.

Key Dates

Start date
Nov 13, 2018
Status verified
Jan 2026
Primary completion
Jan 1, 2027
Completion
Jan 5, 2029

Study Design

Enrollment
48 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

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.

Primary Outcome Measure

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

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Masonic Cancer Center at University of MinnesotaMinneapolisMinnesota55455
Lisa Burke, RN
[email protected]
612-273-8482

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