Study to Assess Safety, Tolerability, Pharmacokinetics and Antitumor Activity of AZD4573 in Relapsed/Refractory Haematological Malignancies

NCT ID: NCT03263637

Last Updated: 2021-10-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-24
• Study Completion Date: 2021-09-30

Brief Summary

The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary antitumor activity of AZD4573 in subjects with relapsed or refractory haematological malignancies.

Conditions

Relapsed or Refractory Haematological Malignancies Including; Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; High Risk Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Richter's Syndrome; B-cell Non-Hodgkin Lymphoma; T-cell Non-Hodgkin Lymphoma; Small Lymphocytic Lymphoma; Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: (Cohort 1-3)

dose level 1-3 in subjects with relapsed or refractory haematological malignancies excluding AML/ALL/high-risk MDS/CMML/CLL.

Group Type: EXPERIMENTAL

AZD4573

Intervention Type: DRUG

AZD4573 will be administered as a intravenous (IV) infusion.

Arm B: (Cohort 1-3)

dose level 1-3 in subjects with relapsed or refractory AML, ALL, high-risk MDS, CMML, CLL and Richter's syndrome.

Group Type: EXPERIMENTAL

AZD4573

Intervention Type: DRUG

AZD4573 will be administered as a intravenous (IV) infusion.

Interventions

AZD4573

AZD4573 will be administered as a intravenous (IV) infusion.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with histologically confirmed, relapsed or refractory haematological malignancies. Patients will include but are not limited to the following: Arm A : B-cell Non-Hodgkin lymphoma , T-cell Non-Hodgkin lymphoma , Small lymphocytic lymphoma (SLL) , Multiple myeloma (MM) Arm B: CLL (chronic lymphocytic leukaemia), Richter's syndrome , AML/secondary AML, ALL , High-risk myelodysplastic syndrome (MDS), CMML (chronic myelomonocytic leukemia)

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
• Must have received at least 2 prior lines of therapy
• Documented active disease requiring treatment per respective NCCN/ESMO guideline that is relapsed or refractory defined as: Recurrence of disease after response to prior line(s) of therapy Or progressive disease after completion of the treatment regimen preceding entry into the study
• Adequate hematologic, hepatic and renal function
• Women should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test before start of dosing if of child-bearing potential or must have evidence of nonchildbearing potential
• Men should be willing to use barrier contraception (ie, condoms) and refrain from sperm donation during and after the conduct of the trial.

Exclusion Criteria

• Treatment with any of the following: any other chemotherapy, immunotherapy or anticancer agents within 2 weeks, any hematopoietic growth factors (e.g., filgrastim; [G-CSF] or sargramostin [GM-CSF]) within 7 days of the first dose of investigational product or pegylated G-CSF (pegfilgrastim) or darbepoetin within 14 days, any full-dose level anti-coagulation treatment sufficiently prior to treatment that INR is <1.5 (DVT/PE prophylaxis dose is allowed) or Major surgery (excluding placement of vascular access) within 4 weeks (with regard to the first dose of study treatment on this protocol).
• With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment.
• Presence of, or history of, CNS lymphoma, leptomeningeal disease or spinal cord compression.
• History of prior nonhematologic malignancy with exceptions mentioned in protocol
• Patients with any of the following: evidence of severe or uncontrolled systemic disease, asecretory myeloma, a known history of infection with human immunodeficiency virus (HIV), serological evidence of active Hepatitis B infection, cardiac abnormalities as mentioned in the protocol, previous allogeneic bone marrow transplant, adrenal gland insufficiency or pancreatitis.
• History of severe allergic or anaphylactic reactions to BH3 mimetics or history of hypersensitivity to active or inactive excipients of AZD4573.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Aachen, , Germany

Research Site

Bonn, , Germany

Research Site

Göttingen, , Germany

Research Site

Heidelberg, , Germany

Research Site

Ulm, , Germany

Research Site

Amsterdam, , Netherlands

Research Site

Nieuwegein, , Netherlands

Research Site

Cardiff, , United Kingdom

Research Site

Manchester, , United Kingdom

Research Site

Plymouth, , United Kingdom

Research Site

Southampton, , United Kingdom

Research Site

Sutton, , United Kingdom

Countries

Germany; Netherlands; United Kingdom

References

Cidado J, Boiko S, Proia T, Ferguson D, Criscione SW, San Martin M, Pop-Damkov P, Su N, Roamio Franklin VN, Sekhar Reddy Chilamakuri C, D'Santos CS, Shao W, Saeh JC, Koch R, Weinstock DM, Zinda M, Fawell SE, Drew L. AZD4573 Is a Highly Selective CDK9 Inhibitor That Suppresses MCL-1 and Induces Apoptosis in Hematologic Cancer Cells. Clin Cancer Res. 2020 Feb 15;26(4):922-934. doi: 10.1158/1078-0432.CCR-19-1853. Epub 2019 Nov 7.

Reference Type: DERIVED

PMID: 31699827 (View on PubMed)

Other Identifiers

D8230C00001

Identifier Type: -

Identifier Source: org_study_id