RecruitingPhase 1

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

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)

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
Up to 80 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Time periods mentioned: 12 weeks

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "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."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests the side effects and best dose of donor T cells changed to find a marker called HA-1 on leukemia cells. T cells are immune cells that help fight disease. The study is for people whose acute leukemia stays, comes back, or does not respond to treatment after a donor stem cell transplant.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be 0 to 80 years old when joining.
  • Have the HLA-A*0201 marker and the HA-1(H) gene type, as shown by testing.
  • Have an adult stem cell donor who meets the study’s matching rules. The donor must either lack HLA-A*0201 or have HLA-A*0201 but lack HA-1(H).
  • Be having or have had a donor stem cell transplant for an allowed blood cancer: acute leukemia, myelodysplastic syndrome (MDS), chronic or juvenile myelomonocytic leukemia, or certain chronic myeloid leukemia (CML).
  • For CML, have a past fast-growing phase called blast crisis and cancer that returns or resists treatment after transplant. Small but rising amounts of cancer must meet testing rules, and targeted drugs must not work or be an option.
  • Agree to join after learning about the study. A parent or legal representative must give permission for children under 18; adults who cannot make this decision may use a legal representative. Donors must be at least 18 and able to agree.
  • Agree to follow-up visits for up to 15 years if you receive the study T cells.
  • Other cancer treatments after transplant do not always prevent joining. There is no required activity-level score, but low activity levels may delay T cell treatment.

Who can't join

  • Have a medical or mental health condition that the study doctor believes makes cell therapy unsuitable.
  • Be able to have children but unwilling to use birth control during treatment and for 12 months afterward.
  • Be expected to live less than 3 months because of an illness other than leukemia.
  • Have grade IV acute or severe long-term graft-versus-host disease (GVHD), when donor cells attack your body. The study doctor may allow exceptions if the diagnosis is uncertain or the condition has greatly improved and stayed better.
  • Organ damage does not always prevent joining, but it may delay T cell treatment.
  • Donors cannot test positive for HIV-1, HIV-2, HTLV-1, or HTLV-2, or have active hepatitis B or C infection.
  • Unrelated donors living outside the United States cannot take part unless their screening, testing, and blood cell collection occur at a qualified center linked to the National Marrow Donor Program and are arranged through that program.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility 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

Study sites (1)

WA