Using donor T cells to treat acute myeloid leukemia and myelodysplastic syndrome

Administration of Donor Derived Multi-Tumor-Associated Antigen (TAA)- Specific T Cells to Patients With AML or MDS (ADSPAM)

This study is testing whether T cells from a donor can help patients with acute myeloid leukemia or myelodysplastic syndrome that hasn't responded to other treatments by making the T cells attack the cancer cells.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 44 (estimated)
• Sex: All
• Sponsor: Baylor College of Medicine (Academic / other)
• Drugs / interventions: prednisone, chemotherapy, radiation
• Locations: 2 sites (Houston, Texas and 1 other locations)
• Trial ID: NCT02494167 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of donor-derived multi tumor-associated antigen (TAA)-specific T cells as a treatment for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that has relapsed or is resistant to standard therapies. The approach involves collecting blood from the patient's stem cell donor and stimulating the donor's T cells to recognize and attack cancer cells expressing specific tumor proteins. After confirming the T cells' effectiveness against the patient's cancer, they are administered via intravenous infusion. Patients will be monitored for changes in cancer cell levels following treatment.

Who should consider this trial

Good fit: Ideal candidates include patients who have undergone allogeneic hematopoietic stem cell transplant and have relapsed or refractory AML or MDS.

Not a fit: Patients who have not undergone a stem cell transplant or have other types of leukemia may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with difficult-to-treat AML or MDS.

How similar studies have performed: Previous studies using T cell therapies for other cancers have shown promising results, suggesting potential success for this novel approach.

Eligibility criteria

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).

Where this trial is running

Houston, Texas and 1 other locations

• Houston Methodist Hospital — Houston, Texas, United States (Recruiting)
• Texas Children's Hospital — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Premal Lulla, MD — Baylor College of Medicine
• Study coordinator: Premal Lulla, MD

Conditions Acute Myeloid Leukemia; Myelodysplastic Syndrome; MultiTAA Specific T cells