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

September 9, 2026 updated by: Fred Hutchinson Cancer Center

A Phase II Prospective Study Evaluating Selective Depletion of CD45RA⁺ Naïve T Cells (TND) From Peripheral Blood Stem Cell Grafts for the Prevention of Graft-Versus-Host Disease in Older Patients With Acute Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation (HCT)

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

OUTLINE:

Patients receive cyclophosphamide intravenously (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.

After completion of study treatment, patients are followed up at day 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77, then weekly until 1 completion of year 1 as well as at day 180 and 270, at 1.5 and 2 years and then periodically until 5 years post day 0.

Study Type

Interventional

Enrollment (Estimated)

52

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutch/University of Washington Cancer Consortium
        • Contact:
        • Principal Investigator:
          • Phuong Vo, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
    • Alcoholic hepatitis.
    • Esophageal varices or history of variceal bleeding.
    • Hepatic encephalopathy.
    • Uncorrectable synthetic dysfunction (prolonged prothrombin time).
    • Ascites due to portal hypertension.
    • Bridging fibrosis.
    • Bacterial or fungal liver abscess.
    • Biliary obstruction.
    • Chronic viral hepatitis with total bilirubin >3 mg/dL.
    • Symptomatic biliary disease
  • PARTICIPANT: Active infectious disease requiring deferral of conditioning (per Infectious disease consult). Upper respiratory tract infection is not considered to represent an uncontrolled infection in this context
  • PARTICIPANT: Fungal infection with radiologic progression despite appropriate antifungal therapy
  • PARTICIPANT: Viral infection risk: HIV-1, HIV-2, human T-lymphotropic virus (HTLV) 1 or HTLV2 positivity or active infectious hepatitis
  • PARTICIPANT: Patients with active central nervous system (CNS) leukemia at the time of treatment are excluded. A history of CNS leukemia is allowed if CNS disease has resolved prior to treatment initiation
  • PARTICIPANT: Weight > 110kg

  • PARTICIPANT: Other malignancies:

    • Active non-hematologic malignancies (except non-melanoma skin cancers).
    • Non-hematologic malignancy in remission but with > 20% risk of recurrence within 5 years.
    • Exclusion does not apply to indolent non-hematologic malignancies not requiring therapy
  • PARTICIPANT: Patients with a life expectancy < 12 months from co-existing disease other than the leukemia or MDS
  • PARTICIPANT: Hypersensitivity to cyclophosphamide, fludarabine, tacrolimus or mycophenolate mofetil (MMF)
  • PARTICIPANT: Inability to provide informed consent
  • PARTICIPANT: Alternative treatment: Patients who are suitable for and willing to receive a standard high intensity (myeloablative) preparative regimen
  • DONOR: Stem cell source restriction: Donors (or centers) that can exclusively provide bone marrow harvests
  • DONOR: Medical contraindications: HIV-1, HIV-2, HTLV-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection

  • DONOR: Preexisting immunoreactivity:

    • Determined per institutional standard practices.
    • For patients with a 10/10 HLA allele-level match, panel reactive antibody (PRA) screens to class I and class II antigens are recommended before HCT. If PRA >10%, then flow cytometric or B- and T-cell cytotoxic crossmatches must be obtained. The donor is excluded if any crossmatch is positive.
    • For patients with a Class I allele mismatch, flow cytometric or B- and T-cell cytotoxic crossmatches must be performed regardless of PRA results. A positive anti-donor cytotoxic crossmatch is an absolute exclusion.
    • Vector homozygosity: Donors are excluded if the patient is homozygous in the graft rejection vector against the donor's mismatched HLA class I allele
  • DONOR: Donors donating outside of the United States of America (USA)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (CD34-selected graft with CD45RA-depleted PBSC)
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.
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • Asta B 518
  • B-518
  • WR-138719
  • B 518
  • B518
  • WR 138719
  • WR138719
  • Frindovyx
Drug: Fludarabine
Given IV
Other Names:
  • Fluradosa
Procedure: Bone Marrow Aspiration
Undergo bone marrow aspiration
Procedure: Bone Marrow Biopsy
Undergo bone marrow biopsy
Other Names:
  • Biopsy of Bone Marrow
  • Biopsy, Bone Marrow
Biological: Allogeneic CD34+-enriched and CD45RA-depleted PBSCs
Given IV
Other Names:
  • Naive T-cell Depleted CD34+ Allogeneic Peripheral Blood Stem Cells
  • Allogeneic Tn-depleted CD34-preserved PBSCs
  • Allogeneic TnD- CD34+ PBSCs
  • Donor-derived Tn Cell Depleted CD34-enriched PBSCs
Radiation: Total-Body Irradiation
Undergo total-body irradiation
Other Names:
  • Total Body Irradiation
  • TBI
  • SCT_TBI
  • Whole Body Irradiation
  • Whole-Body Irradiation
  • Whole Body

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Graft versus host disease (GVHD) relapse-free survival
Time Frame: At 1 year
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: At day 365 and 730 days post transplant
Defined as duration from date of transplant to date of 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 day 365 and 730 days post transplant
Time to relapse
Time Frame: At 1 year post transplant
Defined as duration date of transplant to first documentation of >/=5% leukemic blasts by morphology in bone marrow, circulating leukemic blasts or extramedullary disease (extramedullary disease definite i.e., proven by biopsy or probably based on clinical assessment if biopsy not feasible).
At 1 year post transplant
Treatment related mortality
Time Frame: At day 100 and 365 days post transplant
Defined as death deemed related to transplant and not attributable to the underlying disease. Proportions and their associated 90% confidence intervals will be estimated, confidence intervals will be estimated using the Wilson Score method.
At day 100 and 365 days post transplant
Graft rejection or graft failure rate
Time Frame: Two years post transplant
Graft failure will be operationally defined as failure to achieve an absolute neutrophil count (ANC) ≥ 0.5 × 10^9/L before death or second transplant, or decrease to absolute neutrophil count < 0.1 × 10^9/L for 14 consecutive days (date of graft failure defined as the 14th day) after an established donor graft despite daily administration of granulocyte colony stimulating factor (G-CSF) and ≤ 20% bone marrow cellularity on bone marrow aspirate or biopsy any time in the first 2 years following transplant. Graft rejection will be defined by < 5% of donor T cell (CD3+) chimerism in the absence of relapse.
Two years post transplant
Incidence of acute GVHD
Time Frame: At day 100, 180 and 365 post transplant
Proportions and their associated 90% confidence intervals will be estimated, confidence intervals will be estimated using the Wilson Score method.
At day 100, 180 and 365 post transplant
Incidence of chronic GVHD
Time Frame: At day 365 and 730 post transplant
The Fine-Gray method will be used. Incidence proportions along with 90% confidence intervals will be estimated.
At day 365 and 730 post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Investigators

  • Principal Investigator: Phuong Vo, MD, Fred Hutch/University of Washington Cancer Consortium

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2027

Primary Completion (Estimated)

June 1, 2031

Study Completion (Estimated)

June 1, 2031

Study Registration Dates

First Submitted

September 9, 2026

First Submitted That Met QC Criteria

September 9, 2026

First Posted (Actual)

September 14, 2026

Study Record Updates

Last Update Posted (Actual)

September 14, 2026

Last Update Submitted That Met QC Criteria

September 9, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RG1126340
  • NCI-2026-05117 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • 21164 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe