Azacitidine With or Without Nivolumab or Midostaurin, or Decitabine and Cytarabine Alone in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

Time from date of randomization on study until death from any cause with observations censored on the day of last contact for patients not known to have died.

Time frame: Day of registration on study until death from any cause, assessed for up to 5 years

Population: Due to unexpected toxicities on the Azacitidine + Nivolumab arm during the first two cycles of therapy, the trial was closed early, before the phase II portions was completed and before reaching the phase III portion.

Time from date of randomization on study until death from any cause with observations censored on the day of last contact for patients not known to have died.

Time frame: Day of registration on study until death from any cause, assessed for up to 5 years

Population: The analysis population includes the 76 participants who were eligible and evaluable (26 in the Azacitidine arm, 25 in the Azacitidine+Nivolumab arm, and 25 in the Azacitidine+Midostaurin arm).

Only adverse events that are possibly, probably, or definitely related to study drugs are reported. CTCAE Version 5.0 was used for all AE reporting.

Time frame: Duration of treatment and follow up until death or 5 years post randomization (registration to Step 2).

Population: Participants who were eligible and received at least one dose of protocol treatment.

Cumulative incident endpoints and associations will be assessed using Cox regression models (for cause-specific hazards as appropriate).

Time frame: Date of achievement of a remission until the date of relapse or death, assessed for up to 5 years

Univariate and multivariable regression models will be used to assess potential associations between outcomes (CR, OS, EFS, and RFS) and cytogenetic abnormalities and mutation status (including FLT3-ITD). Regression models including interaction terms with treatment arm will be fit. In addition to analyzing FLT3-ITD as categorical variable used in randomization stratification, we will analyze FLT3-TKD also and evaluate FLT3-ITD allelic ratio as a quantitative variable and as a binary variable using the threshold of 0.50.

Time frame: Up to 5 years

Time from from the date of randomization to the first of: date of primary refractory disease; date of progressive disease; date off protocol therapy without CR or CRi; date of relapse from CR or CRi, or death from any cause; patients not known to have any of these events are censored on the date of last contact.

Time frame: Date of randomization to the first of: date of primary refractory disease; date of progressive disease; date off protocol therapy without CR or CRi; date of relapse from CR or CRi, or death from any cause, assessed for up to 5 years

Population: The analysis population includes the 76 participants who were eligible and evaluable (26 in the Azacitidine arm, 25 in the Azacitidine+Nivolumab arm, and 25 in the Azacitidine+Midostaurin arm).

The prognostic effect of FLT3-ITD (positive versus negative or non-evaluable) with respect to the outcome OS will be evaluated using Cox regression models. The predictive effect of FLT3-ITD (positive versus negative/non-evaluable) with respect to the outcome of OS and the treatments of azacitdine+midostaurin versus azacitidine will be evaluated using a Cox regression model with treatment arm and FLT3-ITD as covariates and including the interaction between the two covariates.

Time frame: Up to 5 years

Will be estimated using the Kaplan-Meier method or Cox regression models. Landmark analyses of different response categories will be evaluated based on dates at which 75% and 90% of patients have achieved a response (with other quantiles analyzed as needed).

Time frame: Day of registration on study until death from any cause, assessed for up to 5 years

Only concurrently randomized patients will be evaluated in comparisons between arms.

Time frame: Up to 5 years

Time from the date of achievement of a remission (defined as patients achieving complete remission (CR), or CR with incomplete hematological recovery (CRi)) until the date of relapse or death from any cause; patients not known to have relapsed or died at last follow-up are censored on the date of last contact.

Time frame: Date of achievement of a remission until the date of relapse or death from any cause, assessed for up to 5 years

Population: The analysis population includes the 17 participants who were eligible and evaluable and had complete response or complete remission with incomplete blood count recovery (CRp/CRi) (6 in the Azacitidine arm, 5 in the Azacitidine+Nivolumab arm, and 6 in the Azacitidine+Midostaurin arm).

#participants(ps) w comp response(resp)(CR), comp remission w incomp bld ct recovery(CRp/CRi), morphol leukemia-free state(MLFS), erythroid&neutrophil&platelet resp(HI-E,HI-N,HI-P), HI-P, marrow comp resp(CRm), stable disease(SD), no resp(NR) CR:BM blasts\<5%; no circ blasts&blasts w Auer rods(AR); no extramedullary disease(ED); ANC≥1x10\^9/L; plt ct≥100x10\^9/L CRp/CRi:CR criteria excl residual neutropenia\<1x10\^9/L or ITP\<100x10\^9/L MLFS:BM blasts\<5%; no blasts w AR, ED, hem recovery rqd HI-E:≥1.5g/dL↑Hb pretx;&RBC trans-depen ps, achieve trans independ or relevant↓RBC trans rqd HI-N:ANC↑pretx≥100%,&an absolute↑of\>500/mm3 pretx HI-P:Absolute↑≥30000/mm3 pretx for ps w plt ct\>20000/mm3 pretx. Ps w plt ct≤20000/mm3 pretx,↑≥100% pretx ct to plt ct\>20000/mm3. Plt trans-depend ps, plt trans independ rqd CRm:CR for BM exam≤5%myeloblasts&marrow myeloblasts↓≥50%pretx SD:Not achieve≥PR, w no evidence prog NR:Not achieve CR,CRi,PR,MLFS,SD, excl ps w death in aplasia or due to indet cause

Time frame: Up to 5 years

Population: The analysis population includes the 76 participants who were eligible and evaluable (26 in the Azacitidine arm, 25 in the Azacitidine+Nivolumab arm, and 25 in the Azacitidine+Midostaurin arm).