PHASE 1B/2 STUDY OF VENETOCLAX WITH LOW-DOSE CYTARABINE IN TREATMENT-NAÏVE PATIENTS AGED ≥65 YEARS WITH ACUTE MYELOGENOUS LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. H Wei A. 06/09/16; 132460; E911
Andrew H Wei
Contributions
Contributions
Abstract
Abstract: E911
Type: Eposter Presentation
Background
Treatment options for older patients (pts) with acute myelogenous leukemia (AML) unfit for intensive chemotherapy are limited. Expected complete remission rates for low-dose cytarabine (LDAC) are about 10% in this population. Targeting the pro-survival molecule BCL-2 has demonstrated clinical efficacy as a therapeutic strategy in various hematologic malignancies. Venetoclax (VEN), a selective BCL-2 inhibitor, shows synergy with cytarabine in several AML cell lines and primary samples.
Aims
The primary objectives of the study include evaluating the safety of VEN administered with LDAC and preliminary estimates of efficacy.
Methods
This is a non-randomized, open-label phase 1/2 dose-escalation/expansion study of VEN + LDAC, in treatment-naïve AML pts ≥65 years not eligible for intensive chemotherapy. Pts receive oral VEN once daily (QD) on days 1‒28 and subcutaneous LDAC 20 mg/m2 QD on days 1‒10 of each 28-day cycle. VEN dose escalation follows a 3 + 3 design; dose-limiting toxicities (DLTs: grade 4 toxicity, platelet count <25,000/μL, or absolute neutrophil count <500/μL within 14 days of last VEN dose) are assessed during cycle 1, up to day 42.
Results
As of Oct 1 2015, 18 pts (66.7% male; median age 74 years) have received LDAC + VEN in the phase 1 portion (VEN 600 mg target dose [n=8]; VEN 800 mg target dose [n=10]). Median time on study is 127.5 (range 30‒272) days; 9 pts (50%) remain on study. DLTs of Grade 4 thrombocytopenia lasting >42 days without evidence of residual leukemia occurred in 2 pts in the VEN 800 mg dose group. The recommended phase 2 dose is 600 mg. Adverse events (AEs; ≥30% prevalence) were nausea (77.8%), anemia (55.6%), febrile neutropenia, neutropenia, fatigue (each 38.9%), vomiting, diarrhea and hypokalemia (each 33.3%). The most common serious AE was febrile neutropenia (33.3%). No clinically significant tumor lysis syndrome was observed. The overall response rate in phase 1 was 44% (complete remission, n=4; complete remission without complete marrow recovery, n=4; resistant disease, n=8; death before evaluation, n=2).
Conclusion
Initial findings suggest that VEN + LDAC has acceptable tolerability and promising clinical activity in older, treatment-naïve AML pts. Available phase 2 updates will be presented.
Session topic: E-poster
Type: Eposter Presentation
Background
Treatment options for older patients (pts) with acute myelogenous leukemia (AML) unfit for intensive chemotherapy are limited. Expected complete remission rates for low-dose cytarabine (LDAC) are about 10% in this population. Targeting the pro-survival molecule BCL-2 has demonstrated clinical efficacy as a therapeutic strategy in various hematologic malignancies. Venetoclax (VEN), a selective BCL-2 inhibitor, shows synergy with cytarabine in several AML cell lines and primary samples.
Aims
The primary objectives of the study include evaluating the safety of VEN administered with LDAC and preliminary estimates of efficacy.
Methods
This is a non-randomized, open-label phase 1/2 dose-escalation/expansion study of VEN + LDAC, in treatment-naïve AML pts ≥65 years not eligible for intensive chemotherapy. Pts receive oral VEN once daily (QD) on days 1‒28 and subcutaneous LDAC 20 mg/m2 QD on days 1‒10 of each 28-day cycle. VEN dose escalation follows a 3 + 3 design; dose-limiting toxicities (DLTs: grade 4 toxicity, platelet count <25,000/μL, or absolute neutrophil count <500/μL within 14 days of last VEN dose) are assessed during cycle 1, up to day 42.
Results
As of Oct 1 2015, 18 pts (66.7% male; median age 74 years) have received LDAC + VEN in the phase 1 portion (VEN 600 mg target dose [n=8]; VEN 800 mg target dose [n=10]). Median time on study is 127.5 (range 30‒272) days; 9 pts (50%) remain on study. DLTs of Grade 4 thrombocytopenia lasting >42 days without evidence of residual leukemia occurred in 2 pts in the VEN 800 mg dose group. The recommended phase 2 dose is 600 mg. Adverse events (AEs; ≥30% prevalence) were nausea (77.8%), anemia (55.6%), febrile neutropenia, neutropenia, fatigue (each 38.9%), vomiting, diarrhea and hypokalemia (each 33.3%). The most common serious AE was febrile neutropenia (33.3%). No clinically significant tumor lysis syndrome was observed. The overall response rate in phase 1 was 44% (complete remission, n=4; complete remission without complete marrow recovery, n=4; resistant disease, n=8; death before evaluation, n=2).
Conclusion
Initial findings suggest that VEN + LDAC has acceptable tolerability and promising clinical activity in older, treatment-naïve AML pts. Available phase 2 updates will be presented.
Session topic: E-poster
Abstract: E911
Type: Eposter Presentation
Background
Treatment options for older patients (pts) with acute myelogenous leukemia (AML) unfit for intensive chemotherapy are limited. Expected complete remission rates for low-dose cytarabine (LDAC) are about 10% in this population. Targeting the pro-survival molecule BCL-2 has demonstrated clinical efficacy as a therapeutic strategy in various hematologic malignancies. Venetoclax (VEN), a selective BCL-2 inhibitor, shows synergy with cytarabine in several AML cell lines and primary samples.
Aims
The primary objectives of the study include evaluating the safety of VEN administered with LDAC and preliminary estimates of efficacy.
Methods
This is a non-randomized, open-label phase 1/2 dose-escalation/expansion study of VEN + LDAC, in treatment-naïve AML pts ≥65 years not eligible for intensive chemotherapy. Pts receive oral VEN once daily (QD) on days 1‒28 and subcutaneous LDAC 20 mg/m2 QD on days 1‒10 of each 28-day cycle. VEN dose escalation follows a 3 + 3 design; dose-limiting toxicities (DLTs: grade 4 toxicity, platelet count <25,000/μL, or absolute neutrophil count <500/μL within 14 days of last VEN dose) are assessed during cycle 1, up to day 42.
Results
As of Oct 1 2015, 18 pts (66.7% male; median age 74 years) have received LDAC + VEN in the phase 1 portion (VEN 600 mg target dose [n=8]; VEN 800 mg target dose [n=10]). Median time on study is 127.5 (range 30‒272) days; 9 pts (50%) remain on study. DLTs of Grade 4 thrombocytopenia lasting >42 days without evidence of residual leukemia occurred in 2 pts in the VEN 800 mg dose group. The recommended phase 2 dose is 600 mg. Adverse events (AEs; ≥30% prevalence) were nausea (77.8%), anemia (55.6%), febrile neutropenia, neutropenia, fatigue (each 38.9%), vomiting, diarrhea and hypokalemia (each 33.3%). The most common serious AE was febrile neutropenia (33.3%). No clinically significant tumor lysis syndrome was observed. The overall response rate in phase 1 was 44% (complete remission, n=4; complete remission without complete marrow recovery, n=4; resistant disease, n=8; death before evaluation, n=2).
Conclusion
Initial findings suggest that VEN + LDAC has acceptable tolerability and promising clinical activity in older, treatment-naïve AML pts. Available phase 2 updates will be presented.
Session topic: E-poster
Type: Eposter Presentation
Background
Treatment options for older patients (pts) with acute myelogenous leukemia (AML) unfit for intensive chemotherapy are limited. Expected complete remission rates for low-dose cytarabine (LDAC) are about 10% in this population. Targeting the pro-survival molecule BCL-2 has demonstrated clinical efficacy as a therapeutic strategy in various hematologic malignancies. Venetoclax (VEN), a selective BCL-2 inhibitor, shows synergy with cytarabine in several AML cell lines and primary samples.
Aims
The primary objectives of the study include evaluating the safety of VEN administered with LDAC and preliminary estimates of efficacy.
Methods
This is a non-randomized, open-label phase 1/2 dose-escalation/expansion study of VEN + LDAC, in treatment-naïve AML pts ≥65 years not eligible for intensive chemotherapy. Pts receive oral VEN once daily (QD) on days 1‒28 and subcutaneous LDAC 20 mg/m2 QD on days 1‒10 of each 28-day cycle. VEN dose escalation follows a 3 + 3 design; dose-limiting toxicities (DLTs: grade 4 toxicity, platelet count <25,000/μL, or absolute neutrophil count <500/μL within 14 days of last VEN dose) are assessed during cycle 1, up to day 42.
Results
As of Oct 1 2015, 18 pts (66.7% male; median age 74 years) have received LDAC + VEN in the phase 1 portion (VEN 600 mg target dose [n=8]; VEN 800 mg target dose [n=10]). Median time on study is 127.5 (range 30‒272) days; 9 pts (50%) remain on study. DLTs of Grade 4 thrombocytopenia lasting >42 days without evidence of residual leukemia occurred in 2 pts in the VEN 800 mg dose group. The recommended phase 2 dose is 600 mg. Adverse events (AEs; ≥30% prevalence) were nausea (77.8%), anemia (55.6%), febrile neutropenia, neutropenia, fatigue (each 38.9%), vomiting, diarrhea and hypokalemia (each 33.3%). The most common serious AE was febrile neutropenia (33.3%). No clinically significant tumor lysis syndrome was observed. The overall response rate in phase 1 was 44% (complete remission, n=4; complete remission without complete marrow recovery, n=4; resistant disease, n=8; death before evaluation, n=2).
Conclusion
Initial findings suggest that VEN + LDAC has acceptable tolerability and promising clinical activity in older, treatment-naïve AML pts. Available phase 2 updates will be presented.
Session topic: E-poster
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