A Phase 1/1b/2a, 3-Part, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Ascending Doses of AZD5991 Monotherapy and in Combination With Venetoclax in Subjects With Relapsed or Refractory Haematologic Malignancies
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- AstraZeneca
- Enrollment
- 70
- Locations
- 1
- Primary Endpoint
- maximum tolerated dose
Study Overview
Brief Summary
This study is a multicenter, open-label, nonrandomized, sequential group, dose-escalation study to assess safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ascending doses of AZD5991 in subjects with relapsed or refractory hematologic malignancies Part 1 of the study is monotherapy dose escalation. Closed November 2020 Part 2 of the study is monotherapy expansion groups for relapsed/refractory chronic lymphocytic leukaemia (CLL), AML/ myelodysplastic syndromes (MDS), and multiple myeloma (MM). Closed November 2020 Part 3 is a sequential, dose-escalation study of the combination of AZD5991 and venetoclax in subjects with relapsed/refractory AML
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Monotherapy AZD5991
Dose escalation - multiple dose levels
Intervention: AZD5991 (Drug)
Monotherapy AZD5991 expansion
Dose expansion
Intervention: AZD5991 (Drug)
AZD5991 + venetoclax
Dose escalation - multiple dose levels
Intervention: AZD5991 + Venetoclax (Drug)
Outcomes
Primary Outcomes
maximum tolerated dose
Time Frame: Minimum observation period is 28 days for the maximum dose cohort
Dose limiting toxicities
Time Frame: Minimum observation period is 28 days per cohort
Incidence of Adverse Events
Time Frame: At every treatment and follow up visit until disease progression. Expected to be for up to 12 months
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
Secondary Outcomes
- Duration of response (DOR)(From time of first dose until discontinuation of AZD5991 monotherapy and AZD5991+venetoclax expected to be for up to 12 months)
- Maximum observed plasma concentration of AZD5991 monotherapy and AZD5991+venetoclax(Predose and through 24 hours postdose)
- Objective response rate (ORR)(From time of first dose until discontinuation of AZD5991 monotherapy and AZD5991+venetoclax expected to be for up to 12 months)
- Area under the concentration-time curve for plasma concentrations of AZD5991 monotherapy and AZD5991+venetoclax(Predose and through 24 hours postdose)
- Progression-free survival (PFS)(From time of first dose until first observation of progression expected to be for up to 12 months)
- Complete remission rate (CRR)(From time of first dose until discontinuation of AZD5991 monotherapy and AZD5991+venetoclax expected to be for up to 12 months)