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NCT03326921 | RECRUITING | Juvenile Myelomonocytic Leukemia

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

Fred Hutchinson Cancer Center

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.

Condition or disease

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 Myeloid 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 Myeloid Leukemia, BCR-ABL1 Positive

Refractory Chronic Myeloid 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

Chronic Myeloid Leukemia, BCR-ABL1 Positive

Intervention/treatment

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

Bone Marrow Aspiration

Biospecimen Collection

Phase

PHASE1

Detailed 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.

Study Type : INTERVENTIONAL
Estimated Enrollment : 24 participants
Masking : NONE
Primary Purpose : TREATMENT
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)
Actual Study Start Date : 2018-02-23
Estimated Primary Completion Date : 2027-10-16
Estimated Study Completion Date : 2028-07-16

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: to 80 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
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
HA-1 T TCR T Cell Immunotherapy for the Treatment of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant

Location Details

NCT03326921

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Locations

RECRUITING

United States, Washington

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States, 98109