Depletion of CD45RA Positive Naive T Cells for the Prevention of Graft Versus Host Disease in Older Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia or Myelodysplastic Syndrome

NCT07819396 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1126340NCI-2026-0511721164
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well removing CD45RA positive naive T cells works to prevent graft versus host disease in older patients undergoing standard of care allogeneic hematopoietic stem cell transplantation for the treatment of acute leukemia or myelodysplastic syndrome (MDS). Allogeneic hematopoietic stem cell transplantation is when healthy cells are collected from a donor and infused into a patient to help the patient's bone marrow make more healthy cells and platelets and help destroy any remaining cancer cells. Giving chemotherapy and total-body irradiation before a stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Sometimes the transplanted cells from a donor can attack the body's normal cells (called graft-versus-host disease). Removing the T cells from the donor cells before the transplant may stop this from happening. Giving CD45RA positive naive T cell depleted allogenic hematopoietic stem cell transplant may prevent graft versus host disease while treating acute leukemia or myelodysplastic syndrome in older adults.

Conditions

Acute Biphenotypic Leukemia; Acute Leukemia; Acute Leukemia of Ambiguous Lineage; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Acute Undifferentiated Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm; Burkitt Leukemia; Burkitt Lymphoma; Chronic Myeloid Leukemia, BCR-ABL1 Positive; Lymphoblastic Lymphoma; Mast Cell Leukemia; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Graft versus host disease (GVHD) relapse-free survival

  Defined as duration between date of transplant and documentation of the date of first occurrence of: relapse, grade III-IV acute GVHD, chronic GVHD, or death due to any cause. Will be estimated using the method of Kaplan Meier. Ninety percent confidence intervals (to be consistent with 1-sided 5% testing) around proportions at milestone time points (e.g. 1-year) will be calculated using the log-log transformation.

  At 1 year

Secondary Outcomes (6)

• Overall survival

  At day 365 and 730 days post transplant

• Time to relapse

  At 1 year post transplant

• Treatment related mortality

  At day 100 and 365 days post transplant

• Graft rejection or graft failure rate

  Two years post transplant

• Incidence of acute GVHD

  At day 100, 180 and 365 post transplant

Study Arms (1)

Treatment (CD34-selected graft with CD45RA-depleted PBSC)

EXPERIMENTAL

Patients receive cyclophosphamide IV, over 1-2 hours on days -6 and -5, fludarabine IV , over 30 minutes on days -6 to -2 and total body irradiation for 1 treatment on day -1 or 0. Patients receive CD34+ enriched peripheral blood stem cells and CD45RA+ depleted cells IV on day 0. Patients undergo bone marrow aspiration/biopsy, echocardiography, and blood sample collection throughout the study.

Biological: Allogeneic CD34+-enriched and CD45RA-depleted PBSCs; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total-Body Irradiation

Interventions

Allogeneic CD34+-enriched and CD45RA-depleted PBSCs BIOLOGICAL

Given IV

Also known as: Allogeneic Tn-depleted CD34-preserved PBSCs, Allogeneic TnD- CD34+ PBSCs, Donor-derived Tn Cell Depleted CD34-enriched PBSCs, Naive T-cell Depleted CD34+ Allogeneic Peripheral Blood Stem Cells

Treatment (CD34-selected graft with CD45RA-depleted PBSC)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (CD34-selected graft with CD45RA-depleted PBSC)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (CD34-selected graft with CD45RA-depleted PBSC)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Frindovyx, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Treatment (CD34-selected graft with CD45RA-depleted PBSC)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (CD34-selected graft with CD45RA-depleted PBSC)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (CD34-selected graft with CD45RA-depleted PBSC)

Total-Body Irradiation RADIATION

Undergo total-body irradiation

Also known as: SCT_TBI, TBI, Total Body Irradiation, Whole Body, Whole Body Irradiation, Whole-Body Irradiation

Treatment (CD34-selected graft with CD45RA-depleted PBSC)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• PARTICIPANT: Age \> 60 years
• PARTICIPANT: Diagnosis of acute leukemia or myelodysplastic syndrome (MDS):
• Acute lymphocytic leukemia (ALL) in first or subsequent morphological remission (\< 5% marrow blasts by morphology).
• Acute myeloid leukemia (AML) in first or subsequent morphological remission (\< 5% marrow blasts by morphology).
• Other acute leukemia or related neoplasm (including but not limited to 'mixed phenotype' 'biphenotypic', 'acute undifferentiated' or 'ambiguous lineage' acute leukemia, blastic plasmacytoid dendritic cell neoplasm, lymphoblastic lymphoma, Burkitt leukemia/lymphoma, mast cell leukemia, chronic myeloid leukemia \[CML\] with blast crisis or other chronic myeloproliferative neoplasm) in first or subsequent morphological remission (\< 5% marrow blasts by morphology).
• Myelodysplastic syndrome (MDS) with a history of excess blasts (≥ approximately 5% in marrow blasts by morphology) and a history of receiving cytoreductive therapy (including but not limited to BCL-2 inhibitors or cytotoxic chemotherapy) within the past 3 months
• PARTICIPANT: Karnofsky performance status (KPS) ≥ 60% at pre-HCT evaluation
• PARTICIPANT: Ability to provide informed consent
• PARTICIPANT: Prior autologous or allogeneic HCT is permitted
• DONOR: Human leukocyte antigen (HLA) matching: HLA-identical related donors or unrelated donors matched for HLA-A, -B, -C, - DRB1, and -DQB1 by high-resolution deoxyribonucleic acid (DNA) typing. A single allele-level mismatch at HLA class I is permitted
• DONOR: Stem cell source: Donors must be able to undergo peripheral blood stem cell (PBSC) collection. Only G-CSF-mobilized PBSC are permitted as the hematopoietic stem cell (HSC) source on this protocol

You may not qualify if:

• PARTICIPANT: Circulating blasts:
• Acute leukemia: circulating abnormal blasts detectable by standard pathology.
• MDS: \> 5% circulating abnormal blasts by standard pathology
• PARTICIPANT: Patients with promyelocytic leukemia (APL)
• PARTICIPANT: Patients with active extramedullary disease are excluded. History of extramedullary disease is allowed if only minimal residual disease is present prior to HCT
• PARTICIPANT: Ejection fraction \< 35% (or shortening fraction \< 26% if ejection fraction \[EF\] unavailable)
• PARTICIPANT: Cardiac insufficiency requiring treatment or symptomatic coronary artery disease
• PARTICIPANT: Patients with shortening fraction \< 26% may enroll if approved by a cardiologist
• PARTICIPANT: Carbon monoxide diffusing capability (DLCO) \< 40%, total lung capacity (TLC) \< 40%, forced expiratory volume in 1 second (FEV1) \< 40%, and/or requiring continuous supplemental oxygen
• PARTICIPANT: If pulmonary function tests (PFTs) cannot be obtained: any patient with room air oxygen saturation \< 89% during a 6-minute walk test (6MWT) will be excluded
• PARTICIPANT: Serum creatinine must be within institutional normal limits
• PARTICIPANT: If serum creatinine \> upper limit of normal, a 24-hour creatinine clearance will be performed; patients are excluded if \< 50 mL/min/1.73 m\^2
• PARTICIPANT: Exclude patients with any of the following:
• Fulminant liver failure.
• Cirrhosis with evidence of portal hypertension.

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Blastic Plasmacytoid Dendritic Cell Neoplasm; Burkitt Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Mast-Cell; Myelodysplastic Syndromes

Interventions

Specimen Handling; Biopsy; Cyclophosphamide; fludarabine; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Histiocytic Disorders, Malignant; Lymphoma; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Mastocytosis, Systemic; Mastocytosis; Mast Cell Activation Disorders

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics

Study Officials

• Phuong Vo, MD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Phuong Vo, MD

CONTACT

206-667-2749; ptvo@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2026
• First Posted: September 14, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031
• Last Updated: September 14, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)