Clinical trial NCT03326921: HA-1 T TCR T Cell Immunotherapy for the Treatment of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant
Official title: Phase I Study of Adoptive Immunotherapy With CD8+ and CD4+ Memory T Cells Transduced to Express an HA-1-Specific T Cell Receptor (TCR) for Children and Adults With Recurrent Acute Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation (HCT)
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
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
Keywords: HA-1
TCR
Immunotherapy
Leukemia
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: HighPass Bio, Inc.
name: PromiCell Therapeutics, Inc.
First posted: 2017-10-31
Enrollment: 24
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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 \< 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.

Primary outcomes:
measure: Feasibility of manufacturing minor H antigen (HA-1) T cell receptor (TCR) CD8+ and CD4+ T cells
timeFrame: At time of T cell infusion (at day 0)
measure: Feasibility of administering minor H antigen (HA-1) T cell receptor (TCR) CD8+ and CD4+ T cells
timeFrame: At time of T cell infusion (at day 0)
measure: Incidence of dose-limiting toxicities of HA-1 T cell receptor (TCR) T cells
timeFrame: Up to 12 weeks after T-cell infusion
Secondary outcomes:
measure: Duration of in vivo persistence of transferred HA-1 T cell receptor (TCR) CD4+ T cells in peripheral blood
timeFrame: Up to 1 year
measure: Duration of in vivo persistence of transferred HA-1 T cell receptor (TCR) CD8+ T cells in peripheral blood
timeFrame: Up to 1 year
measure: Presence, proportion and persistence of HA-1 T cell receptor (TCR) CD4+ T cells in the bone marrow
timeFrame: Up to 1 year
measure: Presence, proportion and persistence of HA-1 T cell receptor (TCR) CD8+ T cells in the bone marrow
timeFrame: Up to 1 year
measure: Specific cytolytic activity of HA-1 T cell receptor (TCR) CD8+ and CD4+ T cells against HLA-A*0201+ HA-1+ target cells before adoptive T cell transfer
timeFrame: At the time of T cell infusion (at day 0)
measure: Specific cytolytic activity of HA-1 T cell receptor (TCR) CD8+ and CD4+ T cells against HLA-A*0201+ HA-1+ target cells after adoptive T cell transfer
timeFrame: Up to 1 year
measure: Reduction of leukemia in the bone marrow in patients who have measurable leukemia in the marrow prior to HA-1 T cell receptor (TCR) T cell infusion
timeFrame: Up to 1 year
measure: Reduction of recipient normal hematopoietic cells in the bone marrow in patients who have measurable recipient normal hematopoietic cells in the marrow prior to HA-1 T cell receptor (TCR) T cell infusion
timeFrame: Up to 1 year
measure: Proportion of patients who develop new or recurrent symptoms or signs of graft-versus-host disease
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Elizabeth Krakow
role: PRINCIPAL_INVESTIGATOR
References: