Back to Trials
NCT03326921PHASE1Recruiting

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

Fred Hutchinson Cancer Center

Start Date

2/23/2018

Completion Date

7/16/2028

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. 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.

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.

Eligibility Criteria

Age Range: No minimum to 80 years

Inclusion Criteria: * 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 * 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 Exclusion Criteria: * 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

Interventions

BIOLOGICAL

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

PROCEDURE

Bone Marrow Aspiration

PROCEDURE

Biospecimen Collection

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Juvenile Myelomonocytic LeukemiaRecurrent Acute Biphenotypic LeukemiaRecurrent Acute Undifferentiated LeukemiaRecurrent Childhood Acute Lymphoblastic LeukemiaRecurrent Childhood Acute Myeloid LeukemiaRefractory Acute Lymphoblastic LeukemiaRefractory Adult Acute Lymphoblastic LeukemiaBlast Phase Chronic Myeloid Leukemia, BCR-ABL1 PositiveRecurrent Blastic Plasmacytoid Dendritic Cell NeoplasmRecurrent Myelodysplastic SyndromeRefractory Blastic Plasmacytoid Dendritic Cell NeoplasmRefractory Myelodysplastic SyndromeAcute Undifferentiated LeukemiaMixed Phenotype Acute LeukemiaRecurrent Chronic Myeloid Leukemia, BCR-ABL1 PositiveRefractory Chronic Myeloid Leukemia, BCR-ABL1 PositiveRecurrent Acute Lymphoblastic LeukemiaRecurrent Acute Myeloid LeukemiaMyelodysplastic SyndromeAcute Myeloid LeukemiaAcute Lymphoblastic LeukemiaAcute Biphenotypic LeukemiaChronic Myeloid LeukemiaChronic Myelomonocytic LeukemiaMinimal Residual DiseaseRecurrent Chronic Myelomonocytic LeukemiaRecurrent Mixed Phenotype Acute LeukemiaLeukemiaChronic Myeloid Leukemia, BCR-ABL1 Positive

Locations

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington 98109

United States