Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft

Part of paid clinical trials in Stanford, California.

Sponsor
Stanford University
Study ID
NCT05088356
Phase
PHASE1
Status
Active Not Recruiting

Conditions

  • Acute Leukemia
  • Advanced Hematologic Malignancies
  • Allogeneic Hematopoietic Cell Transplantation (HCT)
  • Chronic Myelogenous Leukemia
  • Myelodysplastic Syndromes
  • Myeloproliferative Disorders

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Accepted

Interventions

  • Purified regulatory T-cells (Treg) plus CD34+ HSPC — DRUG
    Purified regulatory T-cells (Treg) plus CD34+ hematopoietic progenitor cells ("CD34+ HSPC"), followed by conventional T-cells (Tcon) Manufactured at SCTT Laboratory, dose 1x10\^6 cells/ kg to 3x10\^6 cells/kg
  • Fludarabine — DRUG
    Fludarabine (160 mg/m2)
  • Melphalan — DRUG
    Melphalan (50 mg/m2)
  • CliniMACS CD34 Reagent System — DEVICE
    The CliniMACS® CD34 Reagent System is a medical device that is used in vitro to select and enrich specific cell populations is manufactured by Miltenyi Biotec
  • Tacrolimus — DRUG
    4-6ng/mL
  • Cyclophosphamide — DRUG
    40mg/kg
  • Plerixafor — DRUG
    Dose 0.24 mg/kg, manufactured by Genzyme
  • Filgrastim granulocyte colony-stimulating factor (G-CSF) or equivalent — DRUG
    Single-use vials contain either 300 mcg or 480 mcg filgrastim at a fill volume of 1.0 mL or 1.6 mL
  • Thiotepa — DRUG
    Thiotepa 10 mg/kg
  • Mycophenolate Mofetil (MMF) — DRUG
    MMF 1000 mg BID
  • Ruxolitinib — DRUG
    Ruxolitinib 5 mg BID
  • Sirolimus — DRUG
    5 - 8 ng/mL

Study Details

Reduced intensity conditioning (RIC) has emerged and been increasingly adopted as a modality to allow preparative conditioning pre transplant to be tolerated by older adults or those patients that are otherwise unfit for myeloablative conditioning. In this study, we aim to use RIC followed by matched related/unrelated donor, 7/8 matched related/unrelated donor, or haploidentical donor peripheral blood stem cell transplantation. Standard strategies to control the alloreactivity following HCT utilize immunosuppressive or cytotoxic medications. In this study, we explore donor graft engineering to enrich for immmunoregulatory populations to facilitate post transplantation immune reconstitution while minimizing graft versus host disease (GVHD) with post-transplant immunosuppressive agents.

Key Dates

Start date
Sep 7, 2021
Status verified
May 2026
Primary completion
May 31, 2028
Completion
May 31, 2028

Study Design

Enrollment
66 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm A1: Matched related/matched unrelated donor transplantation (closed)
    Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant:. * Fludarabine (160 mg/m2) * Melphalan (50 mg/m2) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
  • Experimental: Arm B: Haploidentical transplantation (closed)
    Subjects without an identified matched related or matched unrelated donor will receive a haploidentical transplantation with reduced intensity preparative conditioning: -. Fludarabine (160 mg/m2) * Melphalan (100 mg/m2 * TBI (4Gy) Patients will receive GVHD prophylaxis with post-transplant cyclophosphamide and tacrolimus.
  • Experimental: Arm A2: Fully matched (8/8) related/unrelated donor transplantation (closed)
    Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4Gy) All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
  • Experimental: Arm A3: Fully (8/8) matched related/unrelated donor transplantation (closed)
    Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy). All enrolled subjects will receive GVHD prophylaxis with single-agent tacrolimus.
  • Experimental: Arm C1:7/8 mismatched related/unrelated donor transplantation (closed)
    Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (10 mg/kg) * TBI (4 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and mycophenolate mofetil (MMF).
  • Experimental: Arm C2: 7/8 mismatched related/unrelated donor transplantation
    Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus and ruxolitinib.
  • Experimental: Arm A4: 8/8 mismatched related/unrelated donor transplantation
    Subjects will receive reduced intensity preparative chemotherapy conditioning for a matched related/ unrelated donor transplant: * Fludarabine (160 mg/m2) * Thiotepa (7.5 mg/kg) * TBI (2-3 Gy) All enrolled subjects will receive GVHD prophylaxis with tacrolimus

Primary Outcome Measure

Determine the GVHD-free relapse-free survival (GRFS) post-HCT ( Arm-A) [ Time Frame: 12 months ]

Locations (1)

FacilityCityStateZIPSite coordinators
Stanford UniversityStanfordCalifornia94304-

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Stanford University· Stanford, CA

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