This was a Phase 2, open-label, multicenter study evaluating the preliminary efficacy and safety of venetoclax (ABT-199) administered orally in participants with acute myelogenous leukemia (AML).
The primary objective was to evaluate the preliminary efficacy of venetoclax administered orally in participants with relapsed and/or refractory (R/R) acute myelogenous leukemia (AML) or frontline therapy in patients with AML who were unfit for intensive therapy. The secondary objective was to evaluate the preliminary safety of venetoclax administered orally in patients with AML. The first portion of the study was to consist of 19 participants with the objective of evaluating anti-tumor effects and confirming the safety of the regimen. The second portion (expansion) was to consist of 35 additional subjects to evaluate anti-tumor effects and safety and was to commence if an adequate efficacy signal (i.e., ≥ 5/19 achieved complete remission \[CR\], CR with incomplete bone marrow recovery \[CRi\] or partial remission \[PR\]) had been observed in the first portion of the study. The criterion for success would have been met if ≥ 16 of 54 participants achieved remission. The efficacy signal from first portion of the study was deemed insufficient for enrollment into the second portion of the study, as 4 of the 19 subjects achieved CR/CRi. During the trial, a number of participants were in screening at the point of the interim analysis. Given the early signs of clinical activity of venetoclax, disease severity, and prognosis of these participants without available options for therapy, they were allowed to initiate treatment ahead of completion of the interim analysis. Therefore, 32 participants were enrolled. No additional participants were screened or treated after the interim analysis was completed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Tablet
Objective Remission Rate
The objective remission rate (ORR) was defined as the percentage of participants who achieved complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), or partial remission (PR) per the International Working Group criteria for AML. Complete remission (CR) was defined as peripheral neutrophils at least 10˄3/μL, platelets ≥ 10˄5/μL and normocellular bone marrow with ≤ 5% blasts. Complete remission with incomplete bone marrow recovery (CRi) was defined as bone marrow with less than 5% blasts, with peripheral neutrophils of at least 10˄3/μL or platelets ≥ 10˄5/μL. Partial remission (PR) was defined as normalization in peripheral blood neutrophil and platelet counts with at least a 50% decrease in blasts persisting in bone marrow versus baseline.
Time frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier
Complete Remission Rate
The complete remission (CR) rate was defined as the percentage of participants who achieved CR per the International Working Group criteria for AML. Complete remission was defined as peripheral neutrophils at least 10˄3/μL, platelets ≥ 10˄5/μL and normocellular bone marrow with ≤ 5% blasts.
Time frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier
Duration of Remission
Duration of remission was defined as the number of days from the date of first remission (CR, CRi, or PR) per the International Working Group criteria for AML to the earliest recurrence or progressive disease (PD). In this study, the duration of remission analysis was not performed because of the low remission rate, per the Statistical Analysis Plan.
Time frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier
Time to Progression
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Time to progression was defined as the number of months from the date of enrollment to the date of earliest disease progression. If a participant did not experience disease progression, then the data for that participant was censored at the date of the last disease assessment.
Time frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier
Progression-free Survival
Progression-free survival was defined as the number of months from the date of enrollment to the date of earliest progression or death. If a participant did not experience disease progression or death, then the data was censored at the date of the last disease assessment.
Time frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier
Overall Survival
Overall survival was defined as the number of months from the date of enrollment to the date of death for all dosed participants. For participants who did not die, their data were censored at the date of last study visit or the last known date to be alive, whichever was later.
Time frame: Measured up to 2 years after the last subject had enrolled in the study.
Percentage of Participants Who Received Subsequent Stem Cell Transplant
The percentage of participants who received a subsequent allogenic (from a healthy donor) stem cell transplant was summarized.
Time frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier
Rate of Minimal Residual Disease (MRD) Negativity
The rate of minimal residual disease (MRD) response was defined as the percentage of participants who had MRD negative status. Only participants with a reported MRD assessment (negative or positive) from the local laboratory at the investigator site were used in the calculation of MRD response rate.
Time frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier
Complete Remission With Incomplete Marrow Recovery (CRi) Rate
The complete remission with incomplete bone marrow recovery (CRi) rate was defined as the percentage of participants who achieved CRi per the International Working Group criteria for AML. Complete remission with incomplete bone marrow recovery was defined as bone marrow with less than 5% blasts, with peripheral neutrophils of at least 10˄3/μL or platelets ≥ 10˄5/μL.
Time frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier
Complete Remission Rate and Complete Remission With Incomplete Marrow Recovery (CRi) Rate
The complete remission rate and the complete remission with incomplete marrow recovery rate (Cri) was defined as the percentage of participants who achieved complete remission (CR) or complete remission with incomplete bone marrow recovery (CRi), per the International Working Group criteria for AML. Complete remission (CR) was defined as peripheral neutrophils at least 10˄3/μL, platelets ≥ 10˄5/μL and normocellular bone marrow with ≤ 5% blasts. Complete remission with incomplete bone marrow recovery (CRi) was defined as bone marrow with less than 5% blasts, with peripheral neutrophils of at least 10˄3/μL or platelets ≥ 10˄5/μL.
Time frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier