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.
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
- Conditions the study is for
- Juvenile Myelomonocytic Leukemia, Recurrent Acute Biphenotypic Leukemia, Recurrent Acute Undifferentiated Leukemia
- What is being tested?
- CD8+ and CD4+ Donor Memory T-cells-expressing HA1-Specific TCR, Bone Marrow Aspiration and Biospecimen Collection
- Type of treatment
- Injection or infusion, Surgery or procedure
- 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
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
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- 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
United States1 site, 1 recruiting
- 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
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.
- Conditions
- Juvenile Myelomonocytic Leukemia, Recurrent Acute Biphenotypic Leukemia, Recurrent Acute Undifferentiated Leukemia, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Refractory Acute Lymphoblastic Leukemia
- 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 group | Role | What they receive |
|---|---|---|
| Treatment (CD4+ and CD8+ HA-1 TCR T cells) | Experimental | 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 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.
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)
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)
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)
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
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
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
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
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)
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
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
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
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.
- First posted31 Oct 2017
- Study start23 Feb 2018
- Primary completion16 Oct 2027 (estimated)
- Study completion16 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Juvenile Myelomonocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- HighPass Bio, Inc., PromiCell Therapeutics, Inc.
- Responsible party
- Sponsor
- Investigators
- Elizabeth Krakow, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
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