NCT03218683

Study of AZD5991 Alone or in Combination With Venetoclax in Relapsed or Refractory Haematologic Malignancies.

Terminated Phase 1 Last updated 23 September 2022

What this trial tests

Phase 1 trial testing AZD5991 in Relapsed or Refractory Acute Myeloid Leukemia (AML) in 70 participants. Terminated before completion.

Timeline

2 August 2017

Primary endpoint
8 October 2021

8 October 2021

Quick facts

Lead sponsor	AstraZeneca
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	70
Start date	2 August 2017
Primary completion	8 October 2021
Estimated completion	8 October 2021
Sites	10 locations across United States

Drugs / interventions tested

• AZD5991 — full drug profile →
• AZD5991 + Venetoclax — full drug profile →

Conditions studied

• Relapsed or Refractory Acute Myeloid Leukemia (AML) — all drugs for Relapsed or Refractory Acute Myeloid Leukemia (AML) →

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 85, any sex, with Relapsed or Refractory Acute Myeloid Leukemia (AML). Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting apoptosis in cancer therapy.
   Carneiro BA, El-Deiry WS. · · 2020 · cited 1823× · PMID 32203277 · DOI 10.1038/s41571-020-0341-y
2. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.
   Zhong L, Li Y, Xiong L, Wang W, et al · · 2021 · cited 1003× · PMID 34054126 · DOI 10.1038/s41392-021-00572-w
3. Regulated cell death (RCD) in cancer: key pathways and targeted therapies.
   Peng F, Liao M, Qin R, Zhu S, et al · · 2022 · cited 586× · PMID 35963853 · DOI 10.1038/s41392-022-01110-y
4. Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia.
   Tron AE, Belmonte MA, Adam A, Aquila BM, et al · · 2018 · cited 375× · PMID 30559424 · DOI 10.1038/s41467-018-07551-w
5. Apoptosis: A Comprehensive Overview of Signaling Pathways, Morphological Changes, and Physiological Significance and Therapeutic Implications.
   Mustafa M, Ahmad R, Tantry IQ, Ahmad W, et al · · 2024 · cited 264× · PMID 39594587 · DOI 10.3390/cells13221838
6. Mitochondria-associated programmed cell death as a therapeutic target for age-related disease.
   Nguyen TT, Wei S, Nguyen TH, Jo Y, et al · · 2023 · cited 221× · PMID 37612409 · DOI 10.1038/s12276-023-01046-5
7. Targeting MCL-1 in cancer: current status and perspectives.
   Wang H, Guo M, Wei H, Chen Y. · · 2021 · cited 210× · PMID 33883020 · DOI 10.1186/s13045-021-01079-1
8. MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies.
   Ahmadi SE, Rahimi S, Zarandi B, Chegeni R, et al · · 2021 · cited 158× · PMID 34372899 · DOI 10.1186/s13045-021-01111-4