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

PRIMARY OBJECTIVES:

I. To evaluate the feasibility and safety of HA-1 T TCR T cell immunotherapy in approximately
12 children and adolescents and 12 adults with recurrent acute leukemia after allogeneic
hematopoietic stem cell transplantation (HCT).

SECONDARY OBJECTIVES:

I. To determine the in vivo persistence of transferred HA-1 TCR T cells in peripheral blood.

II. To determine the ability of HA-1 TCR T cells to migrate to bone marrow.

III. To evaluate the function of HA-1 TCR T cells before and, if possible, after adoptive T
cell transfer.

IV. To observe whether infusion of HA-1 TCR T cells is followed by a reduction of leukemia
burden.

V. To observe whether infusion of HA-1 TCR T cells is followed by a reduction of recipient
hematopoietic chimerism.

VI. To observe whether infusion of HA-1 TCR T cells is followed by the appearance or
recurrence of signs or symptoms of graft-versus-host disease (GVHD).

OUTLINE: This is a dose-escalation study of CD4+ and CD8+ HA-1 TCR T cells.

Patients receive fludarabine phosphate for 1-3 doses 3-14 days prior to HA-1 TCR T cell
administration. Patients then receive CD4+ and CD8+ HA-1 TCR T cells intravenously (IV) over
1 hour.

After completion of study treatment, patients are followed up closely for 12 weeks and then
every 6 months for years 1-5, and then every year for years 6-15.

Inclusion Criteria:

- 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 present within 30 days prior to enrollment 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 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)