This phase I/II trial studies the side effects of laboratory-treated T cells and to see how well they work in treating patients with high-risk acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelogenous leukemia (CML) that has returned after a period of improvement (relapsed), previously treated with donor stem cell transplant. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop cancer cells from growing. Placing a gene that has been created in the laboratory into a person's T cells may make the body build an immune response to kill cancer cells.
PRIMARY OBJECTIVES: I. Determine the safety and potential toxicities associated with treating patients with high risk or relapsed AML, MDS, and CML after allogeneic hematopoietic cell transplantation (HCT) by adoptive transfer of virus-specific cluster of differentiation (CD)8 T cells genetically-modified to express a high affinity Wilms tumor 1 (WT1)-specific T cell receptor (TCR). II. Determine the anti-leukemic activity associated with treating patients with relapsed AML, MDS and CML after allogeneic HCT by adoptive transfer of virus-specific CD8 T cells genetically-modified to express a high affinity WT1-specific T cell receptor (TCR). SECONDARY OBJECTIVES: I. Determine the in vivo persistence of transferred T cells and ability to migrate to and accumulate in bone marrow. II. Determine the maintenance of TCR expression and function of transduced T cells. OUTLINE: Patients are assigned to 1 of 2 treatment arms. ARM I: Patients with no evidence of leukemia post-HCT receive WT1-sensitized T cells intravenously (IV) over 45 minutes (or longer for patients who are 15-30 kg) on days 0 and 14 and aldesleukin subcutaneously (SC) twice daily (BID) on days 14-28. ARM II: Patients with evidence of AML (minimal residual disease or overt relapse) post-HCT receive cyclophosphamide IV and fludarabine phosphate IV daily on days -4 to -2. Patients also receive WT1-sensitized T cells IV over 45 minutes (or longer for patients who are 15-30 kg) on days 0 and 21 and aldesleukin SC BID on days 14-28. After completion of study treatment, patients are followed up weekly for 4 weeks, at weeks 6 and 8, at 3, 6, 12 months, and then annually for up to 15 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
47
Given SC
Given IV
Given IV
Correlative studies
Given IV
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Anti-leukemic Potential Efficacy, in Terms of Duration of Response (Arm II)
Response is assessed throughout the 1 year post treatment timeframe. Morphologic criteria for response: Complete Response (CR) = Bone Marrow blasts \<5%; no blasts with Auer rods; no extramedullary disease. Transfusion independent. Platelets ≥ 100,000/μl Absolute neutrophil count \>1000/μl (CRi: incomplete hematologic recovery CRp: incomplete platelet recovery) Partial Response (PR) = Decrease of at least 50% in the percentage of blasts to 5-25% in the bone marrow and the normalization of blood counts as for CR. (PRi and PRp if incomplete hematologic or platelet recovery) Stable Disease (SD) = Failure to achieve at least PR, but no evidence of progression for \>4 weeks.
Time frame: Up to 1 year
Efficacy, in Terms of Relapse Rate (Arm I)
Time frame: At 1 year post-transplant
Count of Participants Who Experienced Chronic Graft Versus Host Disease (GVHD) (Arm I)
Time frame: Up to 1 year
Count of Participants Who Experienced Chronic Graft Versus Host Disease (GVHD) (Arm II)
Time frame: Up to 1 year
Count of Participants Who Experienced Grade III-IV Acute Graft Versus Host Disease (GVHD) (Arm II)
Time frame: Up to 1 year following infusion per patient
Count of Participants Who Experienced Grade III-IV Acute Graft-versus-host Disease (GVHD) (Arm I)
Time frame: Up to 1 year
Treatment-related Toxicity Rate (Arm I)
Outcome will be reported as a count of participants that experienced adverse events. Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0
Time frame: Up to 30 days after last study intervention per patient
Treatment-related Toxicity Rate (Arm II)
Outcome will be reported as a count of participants that experienced adverse events. Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0
Time frame: Up to 30 days after last study intervention per patient
Disease-free Survival After T Cell Therapy
Time frame: Up to 1 year
Incidence of Relapse After T Cell Therapy (Arm II)
Time frame: Up to 1 year
Maintenance of T Cell Receptor (TCR) Expression of Transduced T Cells (Arm I) i.e. Persistence
Time frame: Up to 28 days post intervention per patient
Maintenance of Function of Transduced T Cells (Arm I)
Time frame: Up to 28 days post intervention per patient
Time to Progression After T Cell Therapy (Arm I)
Time frame: Up to 1 year
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