Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia (phase 1b dose-escalation and expansion)
Phase 1N = 145NCT02203773
- Population
- Treatment-naive AML, age 65 years or older, ineligible for intensive chemotherapy (median age 74 years; poor-risk cytogenetics in 49%)
- Design
- Multicenter phase 1b dose-escalation and expansion study of venetoclax (400, 800 or 1200 mg daily) with decitabine (20 mg/m2 days 1-5) or azacitidine (75 mg/m2 days 1-7). Single-arm; no randomized comparator. ClinicalTrials.gov lists 212 participants; the abstract reports 145 patients.
- Arms
- Venetoclax + hypomethylating agent (experimental, n = 145): Venetoclax 400, 800 or 1200 mg daily with decitabine or azacitidine
- People
- DiNardo CD
Show the numbers
| Endpoint | Analysis | Venetoclax + hypomethylating agent | Control | Effect |
|---|---|---|---|---|
| CR+CRiAll doses, N = 145Complete remission plus complete remission with incomplete count recovery | exploratoryDiNardo 2019 | 67% | — | Median time on study 8.9 months, as stated in the abstract. The full text (PMC6318429) does not designate a primary efficacy end point for this dose-escalation and expansion study, so the result is labelled exploratory. |
| CR+CRiVenetoclax 400 mg + HMA cohortComplete remission plus complete remission with incomplete count recovery | exploratoryDiNardo 2019 | 73% | — | — |
| OSAll doses, N = 145 | exploratoryDiNardo 2019 | median 17.5 months | — | Median overall survival had not been reached in the 400 mg venetoclax cohort, as the abstract states. The full text gives a 95% CI of 12.3 months to not reached for the all-patient median; the study did not designate a primary efficacy end point, so the result is labelled exploratory. |
| Endpoint | Analysis | Venetoclax + hypomethylating agent | Control | Effect |
|---|---|---|---|---|
| CR+CRiAll doses, N = 145Complete remission plus complete remission with incomplete count recovery | exploratoryDiNardo 2019 | 67% | — | Median time on study 8.9 months, as stated in the abstract. The full text (PMC6318429) does not designate a primary efficacy end point for this dose-escalation and expansion study, so the result is labelled exploratory. |
| CR+CRiVenetoclax 400 mg + HMA cohortComplete remission plus complete remission with incomplete count recovery | exploratoryDiNardo 2019 | 73% | — | — |
| OSAll doses, N = 145 | exploratoryDiNardo 2019 | median 17.5 months | — | Median overall survival had not been reached in the 400 mg venetoclax cohort, as the abstract states. The full text gives a 95% CI of 12.3 months to not reached for the all-patient median; the study did not designate a primary efficacy end point, so the result is labelled exploratory. |
- Venetoclax + hypomethylating agent (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Venetoclax + hypomethylating agent |
|---|---|
| 0 | 100.0% |
| 11 | 64.7% |
| 22 | 41.8% |
| 33 | 27.1% |
| 44 | 17.5% |