Slow enrollment

This is a phase II trial designed to test the safety and efficacy (complete response [CR]) of related donor HLA-haploidentical NK-cell based therapy for the treatment of acute myelogenous leukemia (AML).

Patients with newly diagnosed AML who failed to achieve a complete remission (CR) after one or two standard induction attempts receive after a preparative regimen of cyclophosphamide and fludarabine a single infusion of CD3-/CD19- NK cells or CD3-/CD56+ NK cells followed by a short course of Interleukin-2 (IL-2) to facilitate NK cell survival and expansion.

This trial uses a Simon's two-stage design to estimate the complete remission rate at day +42 post NK cell infusion. The trial includes an initial randomized sub- study of 24 patients during stage 1 to choose which of the enriched NK cell products (CD3-/CD19- versus CD3-/CD56+) should be used to complete the trial based on successful in vivo NK cell expansion. This parameter is defined as 40% donor DNA and 40% of lymphocytes are NK cells at day 7 post infusion OR 20% donor DNA and 20% of lymphocytes are NK cells at day 14 post infusion. Twelve patients will be randomized to each product.

Enrollment Plan:

Stage 1: Enroll 24 patients with 1:1 randomization for NK cell processing (CD3-/CD19- versus CD3-/CD56+) Stage 2: Enroll an additional 17 patients using the optimal NK cell product identified during stage 1.

If neither product achieves success at the end of stage 1, the study will stop and the platform redesigned

Inclusion Criteria:

• Newly diagnosed with acute myelogenous leukemia (except acute promyelocytic leukemia) and has failed one or two prior standard induction attempts. Failure is defined as:
• ≥ 30% bone marrow blasts with at least 20% cellularity at mid-cycle bone marrow biopsy or residual AML on subsequent~ day 28 bone marrow biopsy by morphology, flow, PCR or FISH
• Patients enrolling after only 1 failed induction attempt must meet at least one of the following additional eligibility criteria of high risk: ≥ 60 years of age adverse cytogenetics or molecular characteristics
• AML that progressed out of myelodysplastic syndrome (MDS) is eligible if the patient did not receive treatment directed at the MDS
• HLA-haploidentical related donor (aged 12 to 70 years)
• ≥ 18, but < 75 years of age
• Karnofsky performance status ≥ 60%
• Adequate organ function within 14 days of study registration (30 days for pulmonary and cardiac) as defined in section 4.5
• Ability to be off prednisone and other immunosuppressive drugs for at least 3 days prior to the NK cell infusion (excluding preparative regimen pre-meds)
• No prior hematopoietic transplant
• Not pregnant or lactating
• Sexually active females of childbearing potential and males with partners of child bearing potential must agree to use birth control

Exclusion Criteria:

• Pregnant or lactating as the treatments used in this study includes drugs that are FDA Pregnancy Category D.
• Acute leukemias of ambiguous lineage
• AML that transformed from previously treated myelodysplastic syndromes
• Prior hematopoietic transplant
• New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been cleared by Pulmonary. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections)
• Uncontrolled bacterial, fungal, or viral infections including HIV - chronic asymptomatic viral hepatitis is allowed
• Known hypersensitivity to one or more of the study agents used

Institution conducted study as an independent contractor, supervised by the PI. PI may publish results provided that 12 months have elapsed since the completion of the study and sponsor has not initiated publication of a study report and at least 30 days prior to submission sponsor receives a draft to review. This study did not result in any publications.