Provision of TCRγδ T Cells and Memory T Cells Plus Selected Use of Blinatumomab in Naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation

Part of paid clinical trials in Memphis, Tennessee.

Sponsor
St. Jude Children's Research Hospital
Study ID
NCT02790515
Phase
PHASE2
Status
Active Not Recruiting

Conditions

  • Acute Lymphoblastic Leukemia (ALL)
  • Acute Myeloid Leukemia (AML)
  • Chronic Myeloid Leukemia (CML)
  • Juvenile Myelomonocytic Leukemia (JMML)
  • Myelodysplastic Syndrome (MDS)
  • Myeloid Sarcoma
  • Non-Hodgkin Lymphoma (NHL)

Eligibility Criteria

Sex
ALL
Age
N/A - 21 Years
Healthy Volunteers
Not accepted

Interventions

  • Anti-thymocyte globulin (rabbit) — DRUG
    Given intravenous (IV) prior to transplant on Days -14, -13, -12.
  • Blinatumomab — DRUG
    Given by continuous IV infusion at least 2 weeks post-engraftment. Blinatumomab will be given only to patients with CD19+ malignancies.
  • Cyclophosphamide — DRUG
    Given by IV infusion prior to transplant on Day -9.
  • Fludarabine — DRUG
    Given IV prior to transplant on Days -8, -7, -6, -5, and -4.
  • G-CSF — DRUG
    Given IV or subcutaneous (SQ) following transplant on Days 6 and 7.
  • Melphalan — DRUG
    Given IV prior to transplant on Days -2 and -1.
  • Mesna — DRUG
    Given IV prior to cyclophosphamide administration and at approximately 3, 6, and 9 hours after cyclophosphamide infusion.
  • Rituximab — DRUG
    Given IV prior to transplant on Day -1.
  • Tacrolimus — DRUG
    Given oral (PO) or IV beginning prior to transplant on Day -2. The dose will begin to taper at approximately day +60 after transplant in the absence of GVHD. Tacrolimus was used for the first 5 participants enrolled on study. Subsequent participants receive sirolimus.
  • Thiotepa — DRUG
    Given IV prior to transplant on Day -3.
  • HPC,A Infusion — BIOLOGICAL
    Hematopoietic Progenitor Cell, Apheresis (HPC,A) infusion of TCRɑβ+ depleted cells on day of transplant (Day 0) and HPC,A infusion of CD45RA+ depleted cells on Day +1 following transplant.
  • CliniMACS — DEVICE
    The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
  • Sirolimus — DRUG
    Given orally (PO) starting Day 0. The dose will be tapered off over two weeks starting on Day +42 in the absence of GVHD.

Study Details

This study seeks to examine treatment therapy that will reduced regimen-related toxicity and relapse while promoting rapid immune reconstitution with limited serious graft-versus-host-disease (GVHD) and also improve disease-free survival and quality of life. The investigators propose to evaluate the safety and efficacy of selective naive T-cell depleted (by TCRɑβ and CD45RA depletion, respectively) haploidentical hematopoietic cell transplant (HCT) following reduced intensity conditioning regimen that avoids radiation in patients with hematologic malignancies that have relapsed or are refractory following prior allogeneic transplantation. PRIMARY OBJECTIVE: * To estimate engraftment by day +30 post-transplant in patients who receive TCRɑβ-depleted and CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen without radiation. SECONDARY OBJECTIVES: * Assess the safety and feasibility of the addition of Blinatumomab in the early post-engraftment period in patients with CD19+ malignancy. * Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation. * Estimate incidence and severity of acute and chronic (GVHD). * Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.

Key Dates

Start date
Jul 14, 2016
Status verified
Aug 2025
Primary completion
Jul 1, 2025
Completion
Jul 1, 2026

Study Design

Enrollment
170 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Treatment
    Participants receive a conditioning regimen of antithymocyte globulin (rabbit), cyclophosphamide, mesna, fludarabine, thiotepa, tacrolimus (first 5 participants enrolled), sirolimus (used beginning with 6th enrolled participant), melphalan, rituximab. This is followed by HPC,A infusion (transplant), then by G-CSF and blinatumomab. Cells for infusion are prepared using the CliniMACS System.

Primary Outcome Measure

The number of patients engrafted by day +30 post-transplant [ Time Frame: 30 days post-transplant ]

Locations (1)

FacilityCityStateZIPSite coordinators
St. Jude Children's Research HospitalMemphisTennessee38105-

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By research site
St. Jude Children's Research Hospital· Memphis, TN

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