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

Study identifier:D8230C00001

ClinicalTrials.gov identifier:NCT03263637

EudraCT identifier:2017-000817-22

CTIS identifier:N/A

Study Complete

Official Title

A Phase 1, Open-Label, Multicentre, Non-Randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of AZD4573, a Potent and Selective CDK9 Inhibitor, in Subjects with Relapsed or Refractory Haematological Malignancies

Medical condition

Relapsed or refractory haematological malignancies including

Phase

Phase 1

Healthy volunteers

Study drug

AZD4573

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 24 Oct 2017

Primary Completion Date: 30 Sept 2021

Study Completion Date: 30 Sept 2021

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Sept 2023 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

(cohorts 1, 2, 3):
• 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.
Main

Exclusion Criteria

(cohorts 1,2, 3):
• 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
• Undergone any procedures or experienced any of the conditions listed in protocol exclusion criteria currently or in the preceding 6 months
• 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.

No locations available

Arms	Assigned Interventions
Experimental: 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.	Drug: AZD4573 AZD4573 will be administered as a intravenous (IV) infusion.
Experimental: 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.	Drug: AZD4573 AZD4573 will be administered as a intravenous (IV) infusion.

Documents available

Redacted CSR synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]