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Juvenile Myelomonocytic LeukemiaPhase 1NCT03326921

HA-1 T TCR T Cell Immunotherapy for the Treatment of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant

A Phase 1 study testing CD8+ and CD4+ Donor Memory T-cells-expressing HA1-Specific TCR, Bone Marrow Aspiration and Biospecimen Collection in people with Juvenile Myelomonocytic Leukemia and Recurrent Acute Biphenotypic Leukemia, run by Fred Hutchinson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This phase I trial studies the side effects and best dose of CD4+ and CD8+ HA-1 T cell receptor (TCR) (HA-1 T TCR) T cells in treating patients with acute leukemia that persists, has come back (recurrent) or does not respond to treatment (refractory) following donor stem cell transplant. Read more about this study

Who is it for?
Ages Up to 80 years
What is being tested?
CD8+ and CD4+ Donor Memory T-cells-expressing HA1-Specific TCR, Bone Marrow Aspiration and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
23 Feb 2018to 16 Jul 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 Up to 80 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Subject age 0-80 years at the time of enrollment.
  • Subject must express HLA-A*0201
  • Subject must have the HA-1(H) genotype (RS_1801284: A/G, A/A)
  • Subject must have an adult donor for HCT who is adequately HLA matched by institutional standards (includes HLA-matched related or unrelated donors, and HLA-mismatched family donors, including haploidentical donors) and is either:
  • HLA-A*0201 positive and HA-1(H) negative (RS_1801284: G/G) or
  • HLA-A*0201 negative
Show all 23Show fewer
  • Subjects who are currently undergoing or who previously underwent allogeneic HCT for
  • Acute myeloid leukemia (AML) of any subtype
  • Acute lymphoid leukemia (ALL) of any subtype
  • Mixed phenotype/undifferentiated/any other type of acute leukemia, including blastic plasmacytoid dendritic cell neoplasm
  • Chronic myeloid leukemia with a history of blast crisis and:
  • With relapse or refractory disease (>= 5% marrow blasts, or circulating blasts) at any time after HCT
  • With persistent rising minimal residual disease (defined as detectable disease by morphology, flow cytometry, molecular or cytogenetic testing but < 5% marrow blasts by morphology, no circulating blasts on >= 2 of two consecutive tests), refractory or ineligible for treatment with tyrosine kinase inhibitors at any time after HCT
  • Myelodysplastic syndrome (MDS) of any subtype
  • Chronic myelomonocytic leukemia (CMML)
  • Juvenile myelomonocytic leukemia (JMML)
  • Subjects must be able to understand and be willing to give informed consent; decision-impaired adults may consent with their legally authorized representative; parent or legal representative will be asked to consent for subjects younger than 18 years old
  • Subjects must agree to participate in long-term follow-up for up to 15 years if they are enrolled in the study and receive T cell infusion
  • Subjects who have relapsed or have MRD after HCT may receive other agents for treatment of disease and remain eligible for the protocol
  • A specific performance status score is not required for enrolling on the protocol; a delay in infusion of the HA-1 TCR T cells may be required for subjects with low performance status
  • DONOR SELECTION INCLUSION
  • Donor age >= 18 years
  • Donors must be able to give informed consent

Who cannot join

  • Medical or psychological conditions that would make the subject unsuitable candidate for cell therapy at the discretion of the principal investigator (PI)
  • Fertile subjects unwilling to use contraception during and for 12 months after treatment
  • Subjects with a life expectancy of < 3 months of enrollment from coexisting disease other than leukemia
  • Subjects who have ongoing grade IV acute GVHD or severe chronic GVHD following most recent transplant. Exception: the principal investigator (PI) may make an exception on a case-by-case basis to include such a subject if there is doubt surrounding the GVHD diagnosis and/or sustained significant improvement in GVHD severity
  • The presence of organ toxicities will not necessarily exclude subjects from enrolling on the protocol at the discretion of the PI; however, a delay in the infusion of HA-1 TCR T cells may be required
  • DONOR SELECTION EXCLUSION
  • Donors who are human immunodeficiency virus (HIV)-1, HIV-2, human T-lymphotropic virus (HTLV)-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection
  • Unrelated donor residing outside of the United States of America (USA) unless the donor screening, testing and leukapheresis occur at an National Marrow Donor Program (NMDP)-affiliated and qualified donor center and are facilitated by the NMDP

Trial locations and contacts

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

FHCC Immunotherapy Intake contact

206-606-4668

immunotherapy@fredhutch.org

FHCC Immunotherapy Intake contact

855-557-0555

United States1 site, 1 recruiting

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

    FHCC Immunotherapy Intake, 206-606-4668, immunotherapy@fredhutch.org

    FHCC Immunotherapy Intake, 855-557-0555

    Recruiting

Other trials in United States

About this study

Official title: Phase I Study of Adoptive Immunotherapy With CD8+ and CD4+ Memory T Cells Transduced to Express an HA-1-Specific T Cell Receptor (TCR) for Children and Adults With Recurrent Acute Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation (HCT)

This phase I trial studies the side effects and best dose of CD4+ and CD8+ HA-1 T cell receptor (TCR) (HA-1 T TCR) T cells in treating patients with acute leukemia that persists, has come back (recurrent) or does not respond to treatment (refractory) following donor stem cell transplant. T cell receptor is a special protein on T cells that helps them recognize proteins on other cells including leukemia. HA-1 is a protein that is present on the surface of some peoples' blood cells, including leukemia. HA-1 T cell immunotherapy enables genes to be added to the donor cells to make them recognize HA-1 markers on leukemia cells.

Read the detailed description

OUTLINE:

This is a dose-escalation study of CD4+ and CD8+ HA-1 TCR T cells.

Patients receive lymphodepleting chemotherapy (e.g., fludarabine and cyclophosphamide or debulking regimens as specified in the protocol) ending 2-14 days prior to HA-1 TCR T cell administration. Patients then receive CD4+ and CD8+ HA-1 TCR T cells intravenously (IV).

After completion of study treatment, patients are followed up closely for 12 weeks and then every 6 months for years 1-5, and every year for years 6-15.

Initial study activity was funded in part by HighPass Bio, Inc. Current study activity is funded in part by PromiCell Therapeutics, Inc.

Being tested
CD8+ and CD4+ Donor Memory T-cells-expressing HA1-Specific TCR, Bone Marrow Aspiration, Biospecimen Collection
Keywords
HA-1, TCR, Immunotherapy, Leukemia
Medical subject headings
Leukemia, Myelomonocytic, Juvenile, Leukemia, Biphenotypic, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Blast Crisis, Blastic Plasmacytoid Dendritic Cell Neoplasm, Myelodysplastic Syndromes, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Acute

What participants receive

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

  • CD8+ and CD4+ Donor Memory T-cells-expressing HA1-Specific TCRBiological

    Also called CD8+ and CD4+ Donor Memory T-cells-expressing pRRLSIN iC9-HA1 TCR2-RQR-CD8, HA-1 TCR CD8+ and CD4+ Tm Cells, HA-1 TCR T Cells

    Given IV

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection

    Undergo blood sample collection

Study groups in NCT03326921
Study groupRoleWhat they receive
Treatment (CD4+ and CD8+ HA-1 TCR T cells)ExperimentalPatients receive lymphodepleting chemotherapy (e.g., fludarabine and cyclophosphamide or debulking regimens as specified in the protocol) ending 2-14 days prior to HA-1 TCR T cell administration. Patients then receive CD4+ and CD8+ HA-1 TCR T cells IV.
Receives: Biological: CD8+ and CD4+ Donor Memory T-cells-expressing HA1-Specific TCR; Procedure: Bone Marrow Aspiration; Procedure: Biospecimen Collection

What is being measured

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

  1. Feasibility of manufacturing minor H antigen (HA-1) T cell receptor (TCR) CD8+ and CD4+ T cells

    Proportion of subjects for whom a HA-1 TCR T cell product can be produced.

    Measured: At time of T cell infusion (at day 0)

  2. Feasibility of administering minor H antigen (HA-1) T cell receptor (TCR) CD8+ and CD4+ T cells

    Proportion of subjects for whom a HA-1 TCR T cell product can be administered.

    Measured: At time of T cell infusion (at day 0)

  3. Incidence of dose-limiting toxicities of HA-1 T cell receptor (TCR) T cells

    Toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.

    Measured: Up to 12 weeks after T-cell infusion

Secondary outcomes (9)

  1. Duration of in vivo persistence of transferred HA-1 T cell receptor (TCR) CD4+ T cells in peripheral blood

    Evaluated by tetramer and/or molecular tracking e.g. quantitative polymerase chain reaction (qPCR).

    Measured: Up to 1 year

  2. Duration of in vivo persistence of transferred HA-1 T cell receptor (TCR) CD8+ T cells in peripheral blood

    Evaluated by tetramer and/or molecular tracking e.g. qPCR.

    Measured: Up to 1 year

  3. Presence, proportion and persistence of HA-1 T cell receptor (TCR) CD4+ T cells in the bone marrow

    Evaluated by tetramer and/or molecular tracking e.g. qPCR.

    Measured: Up to 1 year

  4. Presence, proportion and persistence of HA-1 T cell receptor (TCR) CD8+ T cells in the bone marrow

    Evaluated by tetramer and/or molecular tracking e.g. qPCR.

    Measured: Up to 1 year

  5. Specific cytolytic activity of HA-1 T cell receptor (TCR) CD8+ and CD4+ T cells against HLA-A*0201+ HA-1+ target cells before adoptive T cell transfer

    Assessed by in vitro chromium release assay or equivalent cytotoxicity assay.

    Measured: At the time of T cell infusion (at day 0)

  6. Specific cytolytic activity of HA-1 T cell receptor (TCR) CD8+ and CD4+ T cells against HLA-A*0201+ HA-1+ target cells after adoptive T cell transfer

    By in vitro chromium release assay or flow cytometric degranulation assay (CD107a) using samples of peripheral blood and/or bone marrow collected from subjects after adoptive T cell transfer.

    Measured: Up to 1 year

  7. Reduction of leukemia in the bone marrow in subjects who have measurable leukemia in the marrow prior to HA-1 T cell receptor (TCR) T cell infusion

    Quantified by flow cytometry to determine percentage of leukemic cells in the marrow.

    Measured: Up to 1 year

  8. Reduction of recipient normal hematopoietic cells in the bone marrow in subjects who have measurable recipient normal hematopoietic cells in the marrow prior to HA-1 T cell receptor (TCR) T cell infusion

    Quantified by variable number tandem repeat (VNTR) to determine percentage of normal recipient and donor cells in the marrow.

    Measured: Up to 1 year

  9. Proportion of subjects who develop new or recurrent symptoms or signs of graft-versus-host disease

    Assessed using clinical evaluation and standard clinical graft versus host disease (GVHD) grading criteria

    Measured: Up to 1 year

Timeline

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

  1. First posted31 Oct 2017
  2. Study start23 Feb 2018
  3. Primary completion16 Oct 2027 (estimated)
  4. Study completion16 Jul 2028 (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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03326921
Sponsor's protocol ID
9716
Other IDs
NCI-2017-01054, 9716, RG9217022
Status last verified
May 2026
First submitted
5 Oct 2017
Last updated
18 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Krakow EF, Brault M, Summers C, Cunningham TM, Biernacki MA, Black RG, Woodward KB, Vartanian N, Kanaan SB, Yeh AC, Dossa RG, Bar M, Cassaday RD, Dahlberg A, Till BG, Denker AE, Yeung CCS, Gooley TA, Maloney DG, Riddell SR, Greenberg PD, Chapuis AG, Newell EW, Furlan SN, Bleakley M. HA-1-targeted T-cell receptor T-cell therapy for recurrent leukemia after hematopoietic stem cell transplantation. Blood. 2024 Sep 5;144(10):1069-1082. doi: 10.1182/blood.2024024105.

    PubMed 38683966

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CD8+ and CD4+ Donor Memory T-cells-expressing HA1-Specific TCR, Bone Marrow Aspiration and Biospecimen Collection in people with Juvenile Myelomonocytic Leukemia and Recurrent Acute Biphenotypic Leukemia, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 18 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact FHCC Immunotherapy Intake (206-606-4668, immunotherapy@fredhutch.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Feasibility of manufacturing minor H antigen (HA-1) T cell receptor (TCR) CD8+ and CD4+ T cells (time frame: At time of T cell infusion (at day 0)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03326921, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2026.

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