quilt-3.034: non-myeloablative tcra/b deplete haplo hsct with post alt-803 for aml

Conditions: High-Risk Acute Myeloid Leukemia; Treatment-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Myelodysplastic Syndrome

Summary: this is a phase ii multi-institutional therapeutic study of a non-myeloablative t cell receptor (tcr) alpha/beta depleted haploidentical transplantation with post-transplant immune reconstitution using alt-803 for the treatment of high-risk myeloid leukemia (aml), treatment-related/secondary aml, and myelodysplastic syndrome (mds).


Eligibility criteria:
inclusion criteria: * age ≥18 to ≤70 years * meets one of the following disease and risk categories: * high-risk acute myeloid leukemia (aml) with predicted risk of relapse higher than 30%, which includes, but not limited to the following: * patients in morphological remission (cr1 or beyond) with minimal residual disease as quantified either by flow cytometry, or by cytogenetics or molecular markers. * patients with the following karyotypes in morphological cr or cri: eln-intermediate i, adverse, eln-intermediate-ii. (18) (examples include monosomal karyotype, complex karyotype, mutant p53, mutant runx1, mutant asxl1, mutant flt3-itd, mutant dnmt3a, inversion 3, t(6:9), kit mutated core binding factor aml) * treatment-related aml and secondary aml in morphological remission (cr1 or beyond) with minimal residual disease as quantified either by flow cytometry, or by cytogenetics or molecular markers * myelodysplastic syndrome (mds) with \< 5% blasts by morphology and meets at least one of the following: * received intensive induction chemotherapy (i.e. 7+3 or mec) or * progression after 4 cycles of hypomethylating agents * the donor and recipient must be hla identical for at least one haplotype (using high resolution dna based typing) at the following genetic loci: hla-a, hla-b, hla-c, and hla-drb1 * karnofsky performance status ≥ 60% (appendix iv) * adequate organ function within 14 days of study registration (30 days for pulmonary and cardiac) defined as: * hepatic: ast and alt \< 3 x upper limit of institutional normal * renal: estimated glomerular filtration rate (gfr) ≥ 40 ml/min/1.73m2 * pulmonary: oxygen saturation ≥ 90% on room air with no symptomatic pulmonary disease. if symptomatic or prior known impairment dlcocor ≥ 40%. * cardiac: lvef ≥ 40% by echocardiography, muga, or cardiac mri, no uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities * able to be off prednisone or other immunosuppressive medications for at least 3 days prior to transplant (excluding preparative regimen pre-medications) * 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 exclusion criteria: * acute leukemias of ambiguous lineage * allogeneic transplant for aml within the previous 6 months (no time limit for autologous transplant) * active cns disease - if a history of aml related cns involvement, screening csf analysis must be negative * 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 * active autoimmune disease requiring systemic immunosuppressive therapy * history of severe asthma and currently on systemic chronic 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 * active concomitant second malignancy (i.e. has required treatment in the previous 6 months) * known hypersensitivity to any of the study agents * received any investigational drugs within the 14 days before 1st dose of fludarabine

Keywords: aml mds