open label nk cell infusion (fate-nk100) with subq il-2 in adults with aml

Conditions: Refractory Acute Myelogenous Leukemia; Relapsed Acute Myelogenous Leukemia

Summary: this is a phase i open-label dose escalation study of a single infusion of fate-nk100 and a short course of subcutaneous interleukin-2 (il-2) administered after lymphodepleting chemotherapy (cy/flu) in subjects with refractory or relapsed acute myelogenous leukemia (aml). fate-nk100 is a natural killer (nk) cell product that is enriched for nk cells with an "adaptive", or human cytomegalovirus (cmv)-induced, phenotype. the nk cell product is comprised of peripheral blood (pb) leukocytes sourced from a related donor (hla-haploidentical or better but not fully hla-matched) that is seropositive for cytomegalovirus (cmv+), and enriched for adaptive nk cells by depletion of cd3+ (t-lymphocytes) and cd19+ (b-lymphocytes) cells followed by ex-vivo culture expansion.


Eligibility criteria:
inclusion criteria: - ≥18 but ≤ 70 years of age * diagnosis of acute myeloid leukemia (aml) and meets one of the following disease criteria: \* primary induction failure: \*\* de novo aml: no cr after 2, 3 or 4 induction attempts with high dose chemotherapy * secondary aml (from mds or treatment related): no cr after 1, 2 or 3 cycles of high dose chemotherapy * relapsed: * not in cr after 1 or 2 cycles of standard re-induction therapy * relapse diagnosed at the time of the 6 months post-hct standard of care follow-up or later (i.e. based on bone marrow biopsy performed day +170 or later) and without evidence of graft versus host disease (gvhd) * for patients \> 60 years of age, the minimum of 1 cycle of standard chemotherapy is not required. * available hla-matched or better but not fully hla-matched (2/4 or 3/4 antigens) related donor (aged 18 to 75 years) with donor/recipient match based on a minimum of intermediate resolution dna based class i typing of the a and b locus who is cmv seropositive. * karnofsky performance status ≥ 60% * adequate organ function within 14 days of study registration (28 days for pulmonary and cardiac) defined as: * creatinine: estimated glomerular filtration rate (egfr) ≥ 50 ml/min/1.73m\^2 per current institutional calculation formula * hepatic: ast and alt ≤ 3 x upper limit of institutional normal * pulmonary function: oxygen saturation ≥ 90% on room air; pft's required only if symptomatic or prior known impairment - must have pulmonary function \>50% corrected dlco and fev1 * cardiac function: lvef ≥ 40% by echocardiography or muga * no symptomatic active conduction system abnormalities * able to be off prednisone or other immunosuppressive medications for at least 3 days prior to fate-nk100 cell infusion (excluding preparative regimen premedications) * sexually active females of child bearing potential and males with partners of child bearing potential must agree to use effective contraception during therapy and for 4 months after completion of therapy * voluntary written consent prior to the performance of any research related procedures arm specific inclusion criteria high-risk agvhd (arm 1): - pediatric or adult (ages 0-76 years) hct recipients with high-risk acute gvhd, as determined either by the refined mn acute gvhd risk score \[28\]: http://z.umn.edu/mnacutegvhdriskscore or high risk on the basis of blood biomarkers (ann arbor score 3) \[31\]. patients in this arm must start treatment within the first 7 days after onset of high-risk agvhd. or steroid- dependent agvhd (arm 2a): - pediatric or adult (ages 0-76 years) hct recipient with grade ii-iv steroid-dependent acute gvhd, defined as any one of the following: flare of acute gvhd of at least grade ii/iv severity within 8 weeks of tapering down or (off of) immunosuppression for acute gvhd, with the flare occurring on ≤0.5 mg/kg prednisone. this can include late-onset agvhd and overlap syndrome. or steroid-refractory agvhd (arm 2b): - pediatric or adult (ages 0-76 years) hct recipient with grade ii-iv steroid refractory acute gvhd, defined as any one of the following: * no response of acute gvhd after at least 4 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent * progression of acute gvhd within 3 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent * failure to improve to at least grade ii acute gvhd after 14 days of systemic corticosteroids, with initial doses of at least 2 mg/kg prednisone or equivalent * flare of acute gvhd of at least grade ii/iv severity while on steroids at a dose \>0.5/mg/kg/day. this can include late-onset agvhd and overlap syndrome. exclusion criteria: * myocardial infraction (mi) within the previous 6 months * acute leukemias of ambiguous lineage * pregnant or breastfeeding - the agents used in this study include those that fall under pregnancy category d - have known teratogenic potential. women of child bearing potential must have a negative pregnancy test at screening * history of or known active cns involvement with aml * active autoimmune disease requiring systemic immunosuppressive therapy * history of severe asthma and currently on chronic systemic medications (mild asthma requiring inhaled steroids only is eligible) * new or progressive pulmonary infiltrates on screening chest x-ray or chest ct scan unless cleared for study 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-1/2 or active hepatitis c/b - chronic asymptomatic viral hepatitis is allowed * received any investigational agent within the 14 days before the start of study treatment (1st dose of fludarabine)

Keywords: aml