Naive T Cell Depletion to Prevent Chronic Graft-versus-Host Disease in Children and Young Adults with Blood Cancers Undergoing Donor Stem Cell Transplant
Sponsor: Fred Hutchinson Cancer Center
ClinicalTrials ID:NCT03779854
This study is testing if removing a specific type of T cell from donor cells can prevent chronic graft-versus-host disease in children and young adults with blood cancers who are receiving a stem cell transplant from a donor.
Patient Parameters
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Program Overview
This phase II clinical trial is exploring whether removing a specific type of T cell, called naive T cells, from donor stem cells can help prevent chronic graft-versus-host disease (GVHD) in children and young adults with blood cancers. GVHD occurs when the transplanted donor cells attack the recipient's body. By depleting naive T cells from the donor cells before the transplant, researchers hope to reduce the risk of this complication.
Description
Participants in this study are divided into two groups. All participants will receive one of three pre-transplant treatment plans, known as conditioning regimens, to prepare their bodies for the transplant.
Conditioning Regimen A:
- Total body irradiation (TBI) twice daily from days -10 to -7.
- Thiotepa given intravenously (IV) over 3 hours once daily on days -6 and -5.
- Fludarabine IV over 30 minutes once daily from days -6 to -2.
Conditioning Regimen B:
- TBI twice daily from days -8 to -5.
- Fludarabine IV over 30 minutes once daily from days -4 to -2.
- Cyclophosphamide IV over 1 hour once daily on days -3 and -2.
Conditioning Regimen C:
- Fludarabine IV over 30 minutes once daily from days -6 to -2.
- Busulfan IV over 180 minutes once daily from days -5 to -2.
- TBI twice daily on day -1.
Group 1: Participants receive donor stem cells with naive T cells removed on day 0.
Group 2: Participants receive donor bone marrow with all T cells included on day 0.
GVHD Prevention:
- All participants receive tacrolimus IV from days -1 to +50, followed by a gradual reduction if there is no severe GVHD.
- Methotrexate IV is given on days +1, +3, +6, and +11.
After the treatment, participants will have regular follow-up visits to monitor their health and the effectiveness of the treatment.
Eligibility Criteria
Inclusion Criteria
- Must have one of the following blood cancers and be suitable for a donor stem cell transplant:
- Acute lymphoblastic leukemia (ALL) with less than 5% cancer cells in the bone marrow.
- Acute myeloid leukemia (AML) with less than 25% cancer cells in the bone marrow.
- Other acute leukemias with less than 5% cancer cells in the bone marrow.
- Myelodysplastic syndrome (MDS) with excess blasts and has received chemotherapy.
- Aged between 6 months and 26 years.
- Have a matched related or unrelated donor.
- Planned to receive peripheral blood stem cells (PBSC) or bone marrow (BM).
- Have a performance status score of 60% or higher.
- Have adequate heart, lung, liver, and kidney function based on specific medical tests.
- Must provide informed consent or have a legal guardian provide consent.
- Donor must be 14 years or older, matched at 8/8 HLA alleles, and available to donate in the USA.
Exclusion Criteria
- Active central nervous system (CNS) disease unless cleared before treatment.
- Participation in other experimental GVHD prevention studies.
- Body weight over 100 kg for related donors or over 75 kg for unrelated donors without approval.
- HIV-positive.
- Uncontrolled infections unless deemed suitable for transplant by a doctor.
- Life expectancy less than 3 months from other diseases.
- Significant medical conditions making transplant unsuitable.
- Previous stem cell transplants.
- Pregnant or breastfeeding women.
- Unwillingness to use birth control or abstain from sex during and after treatment.
- Known allergies to tacrolimus, fludarabine, or methotrexate.
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