NCT03779854

Naive T Cell Depletion for Preventing Chronic Graft-versus-Host Disease in Children and Young Adults With Blood Cancers Undergoing Donor Stem Cell Transplant

Multi-Center Phase II Randomized Controlled Trial of Naïve T Cell Depletion for Prevention of Chronic Graft-Versus-Host Disease in Children and Young Adults

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 68 (estimated)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 6 Months – 26 Years
• Healthy volunteers: Accepted

Summary

This phase II trial studies how well naive T-cell depletion works in preventing chronic graft-versus-host disease in children and young adults with blood cancers undergoing donor stem cell transplant. Sometimes the transplanted white blood cells from a donor attack the body's normal tissues (called graft versus host disease). Removing a particular type of T cell (naive T cells) from the donor cells before the transplant may stop this from happening.

Detailed description

Patients are randomized to 1 of 2 arms. All patients receive 1 of 3 conditioning regimens. CONDITIONING REGIMEN A: Patients undergo total body irradiation (TBI) twice daily (BID) on days -10 to -7, then receive thiotepa intravenously (IV) over 3 hours once daily (QD) on days -6 and -5, and fludarabine IV over 30 minutes once daily on days -6 to -2. CONDITIONING REGIMEN B: Patients undergo TBI BID on days -8 to -5, then receive fludarabine IV over 30 minutes QD on days -4 to -2, and cyclophosphamide IV over 1 hour QD on days -3 and -2. CONDITIONING REGIMEN C: Patients receive fludarabine IV over 30 minutes QD on days -6 to -2, busulfan IV over 180 minutes QD on days -5 to -2, and undergo total body irradiation BID on day -1. ARM I: Patients receive naive T-cell depleted PBSCs on day 0. ARM II: Patients receive unmanipulated T cell-replete BM on day 0. GVHD PROPHYLAXIS: All patients receive tacrolimus IV on days -1 to +50 followed by a taper in the absence of grade II-IV aGVHD. Patients also receive methotrexate IV on days +1, +3, +6, and +11. Additionally, all patients undergo echocardiography (ECHO) and cerebrospinal fluid (CSF) collection at baseline as well as blood sample collection and bone marrow aspiration with or without biopsy throughout the trial. After completion of study treatment, patients are followed up at days 28, 56, 90, 180, 270, and 365 and then at months 15, 18, 21, and 24.

Conditions

• Acute Biphenotypic Leukemia
• Acute Leukemia
• Acute Leukemia of Ambiguous Lineage
• Acute Lymphoblastic Leukemia
• Acute Undifferentiated Leukemia
• Allogeneic Hematopoietic Stem Cell Transplantation Recipient
• Blastic Plasmacytoid Dendritic Cell Neoplasm
• Blasts Under 25 Percent of Bone Marrow Nucleated Cells
• Blasts Under 5 Percent of Bone Marrow Nucleated Cells
• Mixed Phenotype Acute Leukemia
• Myelodysplastic Syndrome With Excess Blasts-1
• Myelodysplastic Syndrome/Acute Myeloid Leukemia
• Burkitt Leukemia
• Chronic Monocytic Leukemia
• Lymphoblastic Lymphoma
• Mast Cell Leukemia
• Myeloproliferative Neoplasm

Interventions

Type	Name	Description
RADIATION	Total-Body Irradiation	Undergo TBI
DRUG	Thiotepa	Given IV
DRUG	Fludarabine	Given IV
DRUG	Cyclophosphamide	Given IV
DRUG	Busulfan	Given IV
PROCEDURE	Allogeneic Bone Marrow Transplantation	Receive unmanipulated T cell replete BM
DRUG	Tacrolimus	Given IV
DRUG	Methotrexate	Given IV
PROCEDURE	Naive T Cell-Depleted Hematopoietic Stem Cell Transplantation	Receive naive T-cell depleted PBSCs
PROCEDURE	Echocardiography	Undergo ECHO
PROCEDURE	Biospecimen Collection	Undergo CSF and blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy

Timeline

• Start date: 2019-08-29
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2018-12-19
• Last updated: 2025-10-15

Locations

10 sites across 1 country: United States

Regulatory

• FDA-regulated drug study