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

This is an interventional treatment trial for Juvenile Myelomonocytic Leukemia focused on measuring HA-1, TCR, Immunotherapy, Leukemia Read More

Inclusion Criteria:

• Patient age 0-75 years at the time of enrollment. Initially only patients who are >= 16 years old will receive HA-1-TCR T cell infusions on the protocol. Younger patients may be screened, enrolled in the protocol and monitored for relapse but will not be eligible for infusion until at least one patient >=16 years old has been treated and discussed with the Food and Drug Administration (FDA)
• 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.