A Study Evaluating Venetoclax in Combination With Azacitidine in Participants With Treatment-Naïve Higher-Risk Myelodysplastic Syndromes (MDS)
- Interventional
- Active
- NCT02942290
Contact Information
A Phase 1b Dose Escalation Study Evaluating the Safety and Pharmacokinetics of Venetoclax in Combination With Azacitidine in Subjects With Treatment-Naïve Higher-Risk Myelodysplastic Syndromes (MDS)
This is a Phase 1b, open-label, non-randomized, multicenter, dose-finding study evaluating venetoclax in combination with azacitidine in participants with treatment-naïve higher-risk MDS comprising a dose-escalation portion and a safety expansion portion.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers?
No
Inclusion Criteria:
- Participant must have documented diagnosis of untreated de novo MDS with:
- International Prognostic Scoring System (IPSS) risk categories Int-2 or High (minimum IPSS overall score of 1.5) OR Revised IPSS (IPSS-R) categories intermediate, high or very high (score of > 3) and
- Presence of less than 20% bone marrow blasts per bone marrow biopsy/aspirate.
- Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.
Exclusion Criteria:
- Participant has received prior therapy for MDS. (Prior supportive care in form of transfusions or growth factors, etc., is not considered prior therapy).
- Participant has received prior therapy with a BCL-2 Homology 3 (BH3) mimetic.
- Participant has a diagnosis other than previously untreated de novo MDS (as defined in the protocol) including:
- MDS with IPSS risk categories Low or Int-1 (overall IPSS score < 1.5)
- Therapy-related MDS (t-MDS).
- MDS evolving from a pre-existing myeloproliferative neoplasm (MPN).
- MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN.
- Participant has received allogeneic Hematopoietic Stem Cell Transplantation (HSCT) or solid organ transplantation.
- Participant has received a live attenuated vaccine within 4 weeks prior to the first dose of study drug.
- Participant must have documented diagnosis of untreated de novo MDS with:
- International Prognostic Scoring System (IPSS) risk categories Int-2 or High (minimum IPSS overall score of 1.5) OR Revised IPSS (IPSS-R) categories intermediate, high or very high (score of > 3) and
- Presence of less than 20% bone marrow blasts per bone marrow biopsy/aspirate.
- Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.
Exclusion Criteria:
- Participant has received prior therapy for MDS. (Prior supportive care in form of transfusions or growth factors, etc., is not considered prior therapy).
- Participant has received prior therapy with a BCL-2 Homology 3 (BH3) mimetic.
- Participant has a diagnosis other than previously untreated de novo MDS (as defined in the protocol) including:
- MDS with IPSS risk categories Low or Int-1 (overall IPSS score < 1.5)
- Therapy-related MDS (t-MDS).
- MDS evolving from a pre-existing myeloproliferative neoplasm (MPN).
- MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN.
- Participant has received allogeneic Hematopoietic Stem Cell Transplantation (HSCT) or solid organ transplantation.
- Participant has received a live attenuated vaccine within 4 weeks prior to the first dose of study drug.