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 (FHCC)

Status and phase

Enrolling

Phase 1

Conditions

Recurrent Acute Undifferentiated Leukemia

Acute Biphenotypic Leukemia

Recurrent Childhood Acute Lymphoblastic Leukemia

Refractory Myelodysplastic Syndrome

Minimal Residual Disease

Recurrent Chronic Myelomonocytic Leukemia

Mixed Phenotype Acute Leukemia

Recurrent Childhood Acute Myeloid Leukemia

Refractory Acute Lymphoblastic Leukemia

Recurrent Myelodysplastic Syndrome

Refractory Chronic Myeloid Leukemia, BCR-ABL1 Positive

Acute Lymphoblastic Leukemia

Myelodysplastic Syndrome

Recurrent Mixed Phenotype Acute Leukemia

Acute Myeloid Leukemia

Chronic Myelomonocytic Leukemia

Recurrent Acute Lymphoblastic Leukemia

Recurrent Chronic Myeloid Leukemia, BCR-ABL1 Positive

Refractory Adult Acute Lymphoblastic Leukemia

Juvenile Myelomonocytic Leukemia

Recurrent Acute Biphenotypic Leukemia

Leukemia

Blast Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive

Chronic Myeloid Leukemia, BCR-ABL1 Positive

Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm

Chronic Myeloid Leukemia

Recurrent Acute Myeloid Leukemia

Acute Undifferentiated Leukemia

Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm

Treatments

Procedure: Bone Marrow Aspiration

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

Procedure: Biospecimen Collection

Study type

Interventional

Funder types

Other

Identifiers

NCT03326921

RG9217022 (Other Identifier)

9716

NCI-2017-01054 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

24 estimated patients

Sex

All

Ages

Under 80 years old

Volunteers

No Healthy Volunteers

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