Sample size calculation and statistics
REGRESSION
To assess efficacy with respect to the primary endpoint CR/Cri/CRh of Q-HAM during salvage therapy, we will compare the patients in the study to historical controls from previous clinical trials based on the matched threshold-crossing approach [In the proposed design, matched historical control patients from two large IPD meta-analyses datasets of r/r-AML patients will be matched by age, and high-risk cytogenetics in refractory patients. Additionally, first CR duration shorter than 18 months will be used as matching factor in relapsed patients. After the enrolment of 20 patients, the a priori unknown matching rate and the number of matched controls per patient in the intervention group are determined by the interim analysis using an iterative procedure (Krisam J, Weber D, Schlenk RF, Kieser M: Enhancing single-arm phase II trials by inclusion of matched control patients, unpublished). An (non-binding) interim stop for futility is done in case the odds ratio, estimated using a logistic regression model adjusting for the matching parameters, does not exceed a threshold of 1.3. Fitting a logistic regression model on both the trial patients and matching historical controls allows to estimate a treatment effect for the novel intervention as compared to standard treatment [If the trial continues to a second stage, a sample size recalculation is performed using a conditional power argument taking the number of matched partners and observed treatment effect into account. In the final analysis, historical control patients are also matched to the patients from the second stage, and the The sample size required for a fixed design, assuming CR/CRi/CRh rates of 0.55 for the enrolled patients and 0.30 for the historical controls, would be a minimum of 60 assuming a logistic regression is performed at one-sided significance level For the analysis of the primary endpoint, a logistic regression model will be applied to assess the odds ratio of CR/CRi/CRh rate after salvage therapy for patients receiving Q-HAM versus matched controls not receiving Q-HAM. The null hypothesis H0: OR≤1 is tested against its alternative H1: OR>1 at a one-sided significance level of 