MT2014-25: Haplo NK With SQ IL-15 in Adult Relapsed or Refractory AML Patients

Study Overview
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Brief Summary
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A phase II trial of CD3/CD19 depleted, IL-15 activated, donor natural killer (NK) cells in adults and subcutaneous IL-15 given after a preparative regimen for the treatment of relapsed or refractory acute myelogenous leukemia (AML). The primary objective is to study the potential efficacy of NK cells and IL-15 to achieve complete remission while maintaining safety.

Official Title
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MT2014-25: Haploidentical Donor Natural Killer (NK) Cell Infusion With Subcutaneous Recombinant Human IL-15 (rhIL-15) in Adults With Refractory or Relapsed Acute Myelogenous Leukemia (AML)

Conditions
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Acute Myelogenous Leukemia

Intervention / Treatment
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* Biological: IL-15


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Recipient): Meets ONE of the following disease criteria: Primary AML induction failure: no CR after 2 or more induction attempts Relapsed AML or Secondary AML (from MDS or treatment related): not in CR after 1 or more cycles of standard re-induction therapy AML relapsed > 2 months after transplant: No re-induction required, and no more than 1 re-induction cycle is allowed. Relapsed AML for patients > 60 years of age the 1 cycle of standard chemotherapy is not required if either of the following criteria is met: Relapse within 6 months of last chemotherapy BM blast count < 30% within 10 days of starting protocol therapy Available related HLA-haploidentical donor (aged 14 to 75 years) by at least Class I serologic typing at the A&B locus Karnofsky Performance Status ≥ 60% Patients must have adequate organ within 14 days (28 days for pulmonary and cardiac) of study registration Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to NK cell infusion (excluding preparative regimen pre-medications). Agrees to use contraception prior to study entry and for the duration of study participation. Exclusion Criteria (Recipient): Bi-phenotypic acute leukemia. Transplant < 60 days prior to study enrollment. Active autoimmune disease. History of severe asthma Uncontrolled intercurrent illness New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been evaluated with bronchoscopy Pleural effusion large enough to be detectable on chest x-ray. Pregnant women History of HIV, active or chronic hepatitis B, hepatitis C or HTLV-I infection Known hypersensitivity to any of the study agents used Received investigational drugs within the 14 days of study registration. Known active CNS involvement. Criteria For Initial Donor Selection: Related donors (sibling, parent, offspring, parent or offspring of an HLA identical sibling). 14-75 years of age. At least 40 kilogram body weight. In general good health as determined by the evaluating medical provider. HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A&B locus. Not pregnant. Able and willing to undergo apheresis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Preparative Regimen and SubQ rHuIL-15<br>Preparative Regimen of Fludarabine and Cyclophosphamide IL-15 Activation of Donor NK Cells: IL-15 to Facilitate NK Cell Survival and Expansion | Biological: IL-15<br>* Preparative Regimen: Fludarabine 25 mg/m2 x 5 days start day -6 Cyclophosphamide 60 mg/kg x 2 days on day -5 and -4 (if < 4 months from prior transplant, omit day -4 dose) IL-15 Activated Donor NK Cells: The apheresis product (collected day -1) will be enriched for NK cells with the large-scale CliniMacs® device (Miltenyi) by depletion of CD3+ cells to remove T-lymphocytes and depletion of CD19+ cells to remove B-lymphocytes. The NK cell enriched product will be activated by overnight incubation with10 ng/ml IL-15 under GMP conditions and infused on day 0. IL-15 to Facilitate NK Cell Survival and Expansion: IL-15 at 2 mcg/kg subcutaneously (SC) beginning day +1, once a day for 5 days followed by a 2 day rest, and then once a day for 5 days for 10 doses total<br>* Other names: Interleukin-15;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| < 5% Marrow Blast, no Circulating Peripheral Blasts and Neutrophil Count of > 1 x 10^9/L | Without platelet recovery | Day 42 post NK cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In Vivo Expansion (>100) of NK Cells (Defined at CD56+/CD3- Lymphocytes) |  | Day 14 post NK cell infusion | 
| Proportion of Patients Experiencing Grade, 3, 4, and 5 Toxicities (Assessed by CTCAE v. 4) |  | Days 1-5 and Days 8-12, 24 hours after the last IL-15 dose, Day +28, Day +42 | 
| Treatment Related Mortality |  | 6 months post-therapy | 
| Number of Subjects Achieving Complete Response, Defined as in Vivo Donor Derived NK Cell Expansion of > 100 Donor Derived NK Cells. |  | Day 42 post NK cell infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, Relapsed, Refractory