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Patients with no evidence of leukemia or MDS post-HCT receive WT1-sensitized T cells IV over 45 minutes (or longer for patients who are 15-30 kg) on days 0 and 14 and aldesleukin SC BID on days 14-28.

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.

Fludarabine Phosphate

Laboratory Biomarker Analysis

WT1-Sensitized Allogeneic T-Lymphocytes

Aude Chapuis

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.

Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant

Phase I/II Study of Adoptive Immunotherapy After Allogeneic HCT With Virus Specific CD8+ T Cells That Have Been Transduced to Express a WT1-Specific T Cell Receptor for Patients With Relapsed AML

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.

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

National Cancer Institute (NCI)

Fred Hutchinson Cancer Center

Associate Professor, Program in Immunology

Toxicities were according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.

Patients with no evidence of leukemia or MDS post-HCT receive WT1-sensitized T cells IV over 45 minutes (or longer for patients who are 15-30 kg) on days 0 and 14 and aldesleukin SC BID on days 14-28.

Aldesleukin: Given SC

Laboratory Biomarker Analysis: Correlative studies

WT1-Sensitized Allogeneic T-Lymphocytes: Given IV

Arm I (High-risk for Relapse After HCT)

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.

Aldesleukin: Given SC

Cyclophosphamide: Given IV

Fludarabine Phosphate: Given IV

Laboratory Biomarker Analysis: Correlative studies

WT1-Sensitized Allogeneic T-Lymphocytes: Given IV

Arm II (Relapsed After HCT)

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Aude Chapuis

Patients who have an HLA type for which T cells can be generated receive avelumab IV over 1 hour every 2 weeks for 12 months. Patients also receive MHC class I up-regulation intervention as in Group 1 between 7-10 days after the first infusion of avelumab and 2-5 days before the first infusion of MCPyV TAg-specific polyclonal autologous CD8+ T cells. Patients receive two infusions of MCPyV TAg-specific polyclonal autologous CD8+ T cells IV over 60-120 minutes.

Group 2 (Avelumab, MHC Class I Up-regulation, T Cells)

4 patients in Arm II did not relapse and were not assessed. 1 pt progressed at their D365 visit timepoint which landed on D367. They were included in the count of participants that passed within their 1 year follow-up timeframe.

Anti-leukemic Potential Efficacy, in Terms of Duration of Response (Arm II)

Patients who do not have a HLA type for which T cells can be generated or for whom T cells cannot be generated for technical issues receive avelumab intravenously (IV) over 1 hour every 2 weeks for 12 months. Within 7-10 days after completion of 1-3 doses of avelumab, patients receive MHC class I up-regulation intervention comprising either localized radiation therapy or recombinant interferon beta via intra-tumor injection.

Group 1 (Avelumab and MHC Class I Up-regulation)

No patients in Arm I relapsed, so overall number of participants analyzed is 0

Efficacy, in Terms of Relapse Rate (Arm I)

Count of Participants Who Experienced Chronic Graft Versus Host Disease (GVHD) (Arm I)

Count of Participants Who Experienced Chronic Graft Versus Host Disease (GVHD) (Arm II)

2 patients were unevaluable for this outcome due to old documentation, unable to discern if the patient had acute GvHD greater than or equal to grade 3.

Count of Participants Who Experienced Grade III-IV Acute Graft Versus Host Disease (GVHD) (Arm II)

All patients were evaluated for aGvHD greater than or equal to Grade 3

Count of Participants Who Experienced Grade III-IV Acute Graft-versus-host Disease (GVHD) (Arm I)

Treatment-related Toxicity Rate (Arm I)

Treatment-related Toxicity Rate (Arm II)

Disease-free Survival After T Cell Therapy

Incidence of Relapse After T Cell Therapy (Arm II)

Maintenance of T Cell Receptor (TCR) Expression of Transduced T Cells (Arm I) i.e. Persistence

Maintenance of Function of Transduced T Cells (Arm I)

No patients analyzed because no patients relapsed in Arm I

Time to Progression After T Cell Therapy (Arm I)

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant	NCT01640301	Recurrent Adult... Recurrent Child... Secondary Acute... Therapy-Related... Donor Hematopoietic C... HLA-A*0201 Posi... Recurrent Acute...	Aldesleukin Cyclophosphamid... Fludarabine Pho... Laboratory Biom... WT1-Sensitized ...	-	Fred Hutchinson Cancer Center
Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant	NCT01640301	Recurrent Adult... Recurrent Child... Secondary Acute... Therapy-Related... Donor Hematopoietic C... HLA-A*0201 Posi... Recurrent Acute...	Aldesleukin Cyclophosphamid... Fludarabine Pho... Laboratory Biom... WT1-Sensitized ...	-	Fred Hutchinson Cancer Center

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