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

Launched by FRED HUTCHINSON CANCER CENTER · Oct 25, 2017

Keywords

ClinConnect Summary

This clinical trial is testing a new type of immunotherapy called HA-1 T cell therapy to treat patients with certain types of acute leukemia that have come back, are not responding to treatment, or persist after a stem cell transplant from a donor. The therapy involves modifying donor immune cells to better recognize and attack leukemia cells by targeting a specific protein called HA-1 found on these cancer cells. This study is in an early phase (Phase 1), focusing on finding the safest and most effective dose of these modified T cells and understanding any side effects.

Patients eligible for this trial are between 0 and 75 years old, have had a stem cell transplant for acute or related leukemias, and have specific genetic markers (HLA-A*0201 and HA-1) that make them suitable for this treatment. They must have a matched adult donor whose cells can be modified for the therapy. Participants should be willing to give consent and agree to long-term follow-up for up to 15 years after receiving the treatment. During the trial, patients can expect close monitoring for side effects and treatment response. This study is currently recruiting patients, and it offers hope for those with leukemia that has been difficult to treat after transplant.

Gender

ALL

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 \< 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)
• • 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.