AZD4573 + Acalabrutinib for Blood Cancer

No longer recruiting at 37 trial locations
AC
Overseen ByAstraZeneca Clinical Study Information Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cancer treatment combination for individuals with certain types of blood cancer that have returned or not responded to previous treatments. It tests AZD4573, an experimental treatment, first alone and then with acalabrutinib, to determine if this combination can combat the cancer. Individuals who have undergone at least one prior treatment for cancers like diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL), and for whom traditional treatments have failed, might be suitable candidates for this trial. Participants should have active disease requiring treatment and no other standard therapy options available. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications, such as strong CYP3A inhibitors or inducers, proton-pump inhibitors, and certain anticoagulants like warfarin, before starting the study treatment. If you are on these medications, you may need to switch to alternatives as specified in the trial protocol.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AZD4573 generally has a manageable safety profile. While some side effects were noted, they were usually not serious. Importantly, studies have not identified any unexpected safety issues with AZD4573, which is reassuring.

When combined with acalabrutinib (also known as Calquence), the safety profile remains promising. Acalabrutinib, used in other treatments, is usually well-tolerated. Previous research has not identified any major safety concerns with this combination. Overall, both treatments have been safe enough in past studies to warrant further testing in new trials.

It's important to remember that new side effects can still occur, but based on current data, the treatments are considered safe.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD4573 + acalabrutinib for blood cancer because these treatments target cancer in innovative ways. Unlike standard treatments like chemotherapy, which attacks all rapidly dividing cells, AZD4573 is a CDK9 inhibitor that specifically disrupts cancer cell survival, potentially leading to more targeted destruction of cancer cells with fewer side effects. Acalabrutinib, on the other hand, is a BTK inhibitor that interrupts signals necessary for cancer cell growth. This combination offers a dual-targeted approach, potentially enhancing effectiveness and reducing the likelihood of resistance compared to existing therapies.

What evidence suggests that this trial's treatments could be effective for blood cancer?

Research has shown that AZD4573 blocks a specific protein essential for cancer cell survival. Studies have demonstrated that AZD4573 effectively stops blood cancer growth in lab models. In this trial, participants will receive AZD4573 either as monotherapy or combined with acalabrutinib, another cancer-fighting drug. Early findings suggest a promising response in patients with difficult-to-treat blood cancers when these drugs are used together. This combination blocks pathways that help cancer cells survive and directly attacks the cancer cells. Although research in humans is ongoing, these early results suggest potential benefits for people with blood cancers that have returned or are resistant to treatment.678910

Are You a Good Fit for This Trial?

This trial is for adults with advanced blood cancers who have tried at least two prior treatments without a cure in sight. They should not be eligible for curative therapies like CAR-T cell therapy and must have specific types of relapsed/refractory (r/r) blood cancers, such as DLBCL or MZL. Participants need to show active disease requiring treatment, adequate organ and bone marrow function, no recent transfusions or growth factor support, and an ECOG status ≤ 2.

Inclusion Criteria

My blood counts are within normal ranges.
My diagnosis was confirmed through a biopsy and detailed lab tests.
I can take care of myself but might not be able to do heavy physical work.
See 17 more

Exclusion Criteria

I have been diagnosed with or currently have progressive multifocal leukoencephalopathy.
You have had a severe allergic or anaphylactic reaction to BH3 mimetics in the past or you are allergic to any of the ingredients in the study treatment.
Serologic status reflecting active hepatitis B or C infection.
See 17 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Dose-setting (Module 1, Part A)

Participants receive ascending doses of AZD4573 in combination with acalabrutinib to identify the maximum tolerated dose and/or Recommended Phase II dose (RP2D)

5 weeks
Weekly visits for dose administration

Expansion (Module 1, Part B)

Participants receive the RP2D of AZD4573 in combination with acalabrutinib in separate expansion cohorts

Variable, based on disease progression

Monotherapy and Combination Treatment (Module 2, Part A)

Participants receive AZD4573 monotherapy followed by combination treatment with acalabrutinib

5 weeks for Cycle 1, 3 weeks for subsequent cycles
Weekly visits for dose administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 2.5 years or until disease progression

What Are the Treatments Tested in This Trial?

Interventions

  • Acalabrutinib
  • AZD4573
Trial Overview The study tests AZD4573 combined with other anti-cancer agents in patients with advanced blood cancer. It's an open-label Phase I/II trial where the drug is given intravenously. The goal is to find the right dose and see how well it works when paired with different cancer medications.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Module 2: Part A and Part BExperimental Treatment2 Interventions
Group II: Module 1: Part A and Part BExperimental Treatment2 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials
4,491
Recruited
290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Parexel

Industry Sponsor

Trials
322
Recruited
137,000+
Peyton Howell profile image

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith profile image

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Citations

AZD4573 Is a Highly Selective CDK9 Inhibitor That ...AZD4573 is currently in phase I clinical trials for evaluation in patients with hematologic malignancies (NCT03263637). There are various studies that have ...
Targeting CDK9 with AZD4573: A Promising Therapeutic ...AZD4573 also showed in vivo efficacy in xenograft models of hematological tumors ... hematologic malignancies, with the first disclosure of ...
3.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/33306391/
Discovery of AZD4573, a Potent and Selective Inhibitor ...Intermittent dosing of compound 24 demonstrated efficacy in xenograft models derived from multiple hematological tumors. Compound 24 is ...
AZD4573 Is a Highly Selective CDK9 Inhibitor That ...... cancers (CRCs) where it is associated with poor prognosis. ... leukemia and is now being studied in a number of other hematologic malignancies.
AstraZeneca advances ambition to redefine care for blood ...Second primary malignancies, including skin cancers and other solid tumors, occurred in 12% of 1029 patients exposed to CALQUENCE in clinical ...
P1126: PHASE 1B/2A STUDY OF AZD4573 (CDK9I) AND ...Results: As of December 2, 2022, 27 pts were treated: 8 in Cohort 1 and 19 in Cohort 2 (11 pts were in the escalation phase and 16 were in the ...
NCT03263637 | Study to Assess Safety, Tolerability, ...The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary antitumor activity of AZD4573 in ...
AZD4573 Is a Highly Selective CDK9 Inhibitor That ...AZD4573 induces rapid cell death across a diverse panel of hematologic cancer cell lines. A, AZD4573 was screened for caspase activation at 6 hours across a ...
AZD4573 in Novel Combinations with Anti-cancer Agents ...A modular Phase I/II, open-label, multicentre study to assess AZD4573 in novel combinations with anti-cancer agents in patients with advanced haematological ...
AZD4573 Elicits Responses in Relapsed/Refractory ...In the phase 1 study, AZD4573 was found to have a manageable safety profile. Notably, no patients with PTCL were treated during the phase 1 ...
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