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Acute Biphenotypic LeukemiaPhase 2NCT07819396

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

A Phase 2 study testing Allogeneic CD34+-enriched and CD45RA-depleted PBSCs, Biospecimen Collection and Bone Marrow Aspiration in people with Acute Biphenotypic Leukemia and Acute Leukemia, run by Fred Hutchinson Cancer Center at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

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Trial 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). Read more about this study

Who is it for?
Any age
What is being tested?
Allogeneic CD34+-enriched and CD45RA-depleted PBSCs, Biospecimen Collection and Bone Marrow Aspiration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
1 siteUnited States
Study dates
1 Jan 2027to 1 Jun 2031
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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)
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  • 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)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Phuong Vo, MD contact

206-667-2749

ptvo@fredhutch.org

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

    Phuong Vo, MD, 206-667-2749, ptvo@fredhutch.org

    Phuong Vo, MD

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Allogeneic CD34+-enriched and CD45RA-depleted PBSCs, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Cyclophosphamide
Medical subject headings
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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allogeneic CD34+-enriched and CD45RA-depleted PBSCsBiological

    Also called 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

    Given IV

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518

    Given IV

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • Total-Body IrradiationRadiation

    Also called SCT_TBI, TBI, Total Body Irradiation, Whole Body

    Undergo total-body irradiation

Study groups in NCT07819396
Study groupRoleWhat they receive
Treatment (CD34-selected graft with CD45RA-depleted PBSC)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At 1 year

Secondary outcomes (6)

  1. Overall survival

    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.

    Measured: At day 365 and 730 days post transplant

  2. Time to relapse

    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).

    Measured: At 1 year post transplant

  3. Treatment related mortality

    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.

    Measured: At day 100 and 365 days post transplant

  4. Graft rejection or graft failure rate

    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.

    Measured: Two years post transplant

  5. Incidence of acute GVHD

    Proportions and their associated 90% confidence intervals will be estimated, confidence intervals will be estimated using the Wilson Score method.

    Measured: At day 100, 180 and 365 post transplant

  6. Incidence of chronic GVHD

    The Fine-Gray method will be used. Incidence proportions along with 90% confidence intervals will be estimated.

    Measured: At day 365 and 730 post transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2026
  2. Study start1 Jan 2027 (estimated)
  3. Primary completion1 Jun 2031 (estimated)
  4. Study completion1 Jun 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
52 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07819396
Sponsor's protocol ID
RG1126340
Other IDs
NCI-2026-05117, 21164
Status last verified
Sep 2026
First submitted
9 Sep 2026
Last updated
14 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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