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Donor-Derived Tumor-Associated Antigen-Specific T Cells in Treating Participants with Relapsed or Refractory acute myeloid leukemia or myelodysplastic syndrome

Trial Status: Active

This phase I trial studies the best dose and how well donor-derived multi-tumor-associated antigen specific T cells work in treating participants with acute myeloid leukemia or myelodysplastic syndrome that have come back or does not respond. Tumor associated antigen-specific T cells are immune system cells that may target cell proteins specific to tumor cells.

Inclusion Criteria

  • Patients will be eligible to receive donor-derived multiTAA-specific T cells following any type of allogeneic HSCT as * Adjuvant therapy for AML/MDS (Group A); or * Treatment for refractory/relapsed or minimal residual AML/MDS disease (Group B) ** Residual disease at the time of transplant or post transplant relapse is defined as polymerase chain reaction (PCR) positivity, specific cytogenetic abnormalities, an abnormal population on flow cytometry or increased blasts on bone marrow biopsy, in the peripheral blood, or any other extramedullary sites * Minimal residual disease (MRD) will be defined as detection in blood, bone marrow, or other tissues any of the following: ** Any leukemia specific marker such as t(8;21); inv 16; t (15;17), t(9;22) or t(4;11) documented in the patient’s leukemia cells pre-transplant on a post-transplant evaluation ** Expression of a leukemia associated antigen known to be a marker for residual disease like WT1 ** A leukemia-specific phenotype (e.g. expression of markers including CD13 and/or CD33 and/or CD117 and/or human leukocyte antigen–antigen D related positive [HLA-DR+]) post-transplant at a level of ≥ 0.01% ** Mixed donor chimerism (> 20%)
  • Life expectancy ≥ 6 weeks
  • Undergoing stem cell transplant at Center for Cell and Gene Therapy (CAGT)
  • Karnofsky/Lansky score of ≥ 50
  • Patient or parent/guardian capable of providing informed consent
  • Bilirubin ≤ 2X upper limit of normal
  • Aspartate transaminase (AST) ≤ 3X upper limit of normal
  • Serum creatinine ≤ 2X upper limit of normal
  • Hemoglobin (Hgb) > 8.0 g/dL (can be transfused)
  • Pulse oximetry of > 90% on room air
  • Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the T cell infusion; male partner should use a condom
  • Available donor-derived multiTAA-specific T cell line
  • No other investigational anti-neoplastic therapy for one month prior to entry in this study
  • DONOR ELIGIBILITY
  • Donors for allogeneic (i.e. HLA matched or mismatched related or unrelated) stem cell transplants who have fulfilled eligibility for and consented to stem cell donation as per the stem cell transplant program's standard operating procedures
  • Subjects must be at least 12 kg or 24 pounds to be eligible for stem cell donation

Exclusion Criteria

  • Patients receiving antithymocyte globulin (ATG) or campath within 28 days of infusion
  • Patients receiving a donor lymphocyte infusion within 4 weeks of planned T cell infusion
  • Less than 30 days post-allogeneic stem cell transplant
  • Severe intercurrent infection
  • Evidence of graft versus host disease (GVHD) > grade II
  • Pregnant or lactating
  • Currently taking corticosteroids (> 0.5 mg/kg/day prednisone or equivalent)

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: ACTIVE
Contact: Premal Lulla
Phone: 713-441-1450
Center for Cell and Gene Therapy
Status: ACTIVE
Contact: Premal Lulla
Phone: 713-441-1450
Texas Children's Hospital
Status: ACTIVE
Contact: Premal Lulla
Phone: 713-441-1450

PRIMARY OBJECTIVES:

I. To determine the safety of an intravenous injection of donor-derived multi-tumor associated antigen (multiTAA)-specific T cells, administered as prophylaxis or treatment of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) post allogeneic hematopoietic stem cell transplant (HSCT).

SECONDARY OBJECTIVES:

I. To obtain information on the expansion, persistence and anti-tumor effects of the adoptively transferred donor-derived multiTAA-specific T cells in patients with AML or MDS.

II. To determine whether multiTAA-specific T cells can increase the spectrum of epitopes/antigens targeted by endogenous T cells (epitope spreading).

OUTLINE: This is a dose escalation study.

Participants receive donor-derived WT1/PRAME/NY-ESO-1/survivin-specific T-lymphocytes intravenously (IV) over 1-10 minutes on day 0. Beginning 4 weeks after infusion, participants who achieve partial response, complete response or stable disease may receive 6 additional doses every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 1, 2, 4, and 8 weeks, then at 3, 6, and 12 months, and then annually for up to 4 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center

Principal Investigator
Premal Lulla

  • Primary ID ADSPAM
  • Secondary IDs NCI-2018-00718
  • Clinicaltrials.gov ID NCT02494167