What's the purpose of this trial?
This research study uses special blood cells called multiple tumor-associated antigen (TAA)-specific T cells (a new experimental therapy) to treat patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) which has come back, or may come back, or has not gone away after standard treatment, including an allogeneic hematopoietic stem cell transplant (HSCT).
The investigators have previously used this sort of therapy to treat Hodgkin or non-Hodgkin lymphomas that are infected with Epstein-Barr virus (EBV). EBV is found in cancer cells of up to half of all patients with Hodgkin and non-Hodgkin lymphoma. This suggests that it may play a role in causing lymphoma. The cancer cells infected by EBV are able to hide from the body's immune system and escape being killed. The investigators previously tested whether special white blood cells (called T cells) that were trained to kill EBV-infected cells could affect these tumors, and in many patients the investigators found that giving these trained T cells causes a complete or partial response.
Other cancers express specific proteins that can be targeted in the same way. The investigators have been able to infuse such tumor-targeted cells into up to 10 patients with lymphoma who do not have EBV, and seen some complete responses. Importantly, the treatment appears to be safe. Therefore, the investigators now want to test whether the investigators can direct these special T cells against other types of cancers that carry similar proteins called tumor-associated antigens (TAAs). These proteins are specific to the cancer cell, so they either do not show up, or show up in low quantities, or normal human cells.
The investigators will grow T cells from patients' stem cell donors in the laboratory in a way that will train them to recognize the tumor proteins WT1, NY-ESO-1, PRAME, and Survivin, which are expressed on most AML and MDS cancer cells. The cells will be infused at least 30 days post-allogeneic stem cell transplant. In this study, the investigators want see whether these cells will be able to recognize and kill cancer cells that express these proteins. These donor-derived multiTAA-specific T cells are an investigational product not yet approved by the U.S. Food and Drug Administration
The purpose of this study is to find the largest safe dose of donor-derived tumor protein multiTAA-specific T cells for patients with AML or MDS.
This trial is currently open and accepting patients.
What will happen during the trial?
You may be able to join this trial if you:
The following criteria is a partial list of reasons why patients may be
eligible to participate in this clinical trial. Further evaluation with a medical professional is
required.
Inclusion Criteria:
1. Patients will be eligible to receive donor-derived multiTAA-specific T cells following any type of allogeneic HSCT as;
(i) Adjuvant therapy for AML/MDS (Group A) or
(ii) 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 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 of any of the following:
(i) 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.
(ii) Expression of a leukemia associated antigen known to be a marker for residual disease like WT1.
(iii) A leukemia-specific phenotype (e.g. expression of markers including CD13 and/or CD33 and/or CD117 and/or HLA-DR+) post-transplant at a level of ≥ 0.01%.
(ix) Mixed donor chimerism (\> 20%).
2. Life expectancy ≥ 6 weeks.
3. Karnofsky/Lansky score of ≥ 50.
4. Patient or parent/guardian capable of providing informed consent.
5. Bilirubin ≤ 2X upper limit of normal.
6. AST ≤ 3X upper limit of normal.
7. Undergoing stem cell transplant at CAGT.
8. Serum creatinine ≤ 2X upper limit of normal.
9. Hgb ≥ 7.0 g/dL (can be transfused).
10. Pulse oximetry of \> 90% on room air.
11. 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.
12. Available donor-derived multiTAA-specific T cell line.
13. No other investigational anti-neoplastic therapy for one month prior to entry in this study.
Exclusion Criteria:
1. Patients receiving ATG or Campath within 28 days of infusion.
2. Patients receiving a Donor Lymphocyte Infusion within 4 weeks of planned T cell infusion.
3. Less than 30 days post-allogeneic stem cell transplant.
4. Severe intercurrent infection.
5. Evidence of GVHD \> Grade II.
6. Pregnant or lactating.
7. Currently taking corticosteroids (\> 0.5 mg/kg/day prednisone or equivalent).
Additional Trial Information
Phase 1
Enrollment: 44 patients (estimated)
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