ha-1 t tcr t cell immunotherapy for the treatment of patients with relapsed or refractory acute leukemia after donor stem cell transplant

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; Refractory Adult Acute Lymphoblastic Leukemia; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm; Recurrent Myelodysplastic Syndrome; Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm; Refractory Myelodysplastic Syndrome; Acute Undifferentiated Leukemia; Mixed Phenotype Acute Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Acute Lymphoblastic Leukemia; Recurrent Acute Myeloid Leukemia; Myelodysplastic Syndrome; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Acute Biphenotypic Leukemia; Chronic Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Minimal Residual Disease; Recurrent Chronic Myelomonocytic Leukemia; Recurrent Mixed Phenotype Acute Leukemia; Leukemia

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.

outline: this is a dose-escalation study of cd4+ and cd8+ ha-1 tcr t cells. patients receive lymphodepleting chemotherapy 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:
inclusion criteria: * patient age 0-75 years at the time of enrollment. * patients must express hla-a\*0201 * patients must have the ha-1(h) genotype (rs_1801284: a/g, a/a) * patients 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 * patients 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 \ = 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) * patients 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 patients younger than 18 years old * patients 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 * patients 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 patients with low performance status donor selection inclusion * donor age \>= 18 years * donors must be able to give informed consent * patients 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 exclusion criteria: * medical or psychological conditions that would make the patient unsuitable candidate for cell therapy at the discretion of the principal investigator (pi) * fertile patients unwilling to use contraception during and for 12 months after treatment * patients with a life expectancy \< 3 months of enrollment from coexisting disease other than leukemia * patients who develop grade iv acute gvhd or severe chronic gvhd following most recent transplant prior to enrollment on the protocol * the presence of organ toxicities will not necessarily exclude patients 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 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 nmdp-affiliated and qualified donor center and are facilitated by the nmdp.

Keywords: ha-1 tcr immunotherapy leukemia