AZD4573 in Novel Combinations with Anti-cancer Agents in Patients with Advanced Haematological Malignancies.

Phase 1

• Conditions: Haematological Malignancies; MedDRA version: 21.1Level: PTClassification code 10066476Term: Haematological malignancySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2020-001642-18-IE
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-03-09
• Last Update Posted: 27 May 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1 Participant must be = 18 years of age at the time of signing the informed consent.
2 Eastern Cooperative Oncology Group (ECOG) performance status of = 2.
3 Must have received at least one prior line of therapy for the treatment of current disease and a clinical study is the best option for next treatment based on prior response and/or tolerability.
- Participants with histologically confirmed, r/r DLBCL (Module 1) who have failed at least two prior therapies for the treatment of current disease, and are not eligible for curative or standard treatment options (including CAR-T cell therapy).
- Participants with histologically confirmed r/r MCL (Module 2) who have failed at least one prior therapy for the treatment of current disease and not be eligible for treatment with curative intent (e.g. allogenic haematopoietic cell transplantation [HCT]). Eligible patients include both BTKi-naïve and BTKi-exposed
4 Documented active disease requiring treatment that is relapsed or refractory as defined in the protocol, including.
5 Adequate haematological function (as defined in the protocol).
6 Adequate organ function at Screening (as defined in the protocol).
7 Uric acid level < upper limit of normal (ULN).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24

Exclusion Criteria

Core
1.Participants with non-secretory myeloma
2.Unresolved non-haematological toxicities (except alopecia) from prior therapy>CTCAE Grade 1 at study treatment start
3.Presence or hist of central nervous system(CNS)lymphoma,leptomeningeal disease or spinal cord compression
4.Prior non-haematological malignancy except for the following
a)Malignancy treated with curative intent with no evidence of active disease for >one year before screening and thought at low risk of recurrence by treating physician b)Adequately treated lentigo maligna melanoma without evidence of disease or adequately controlled non-melanomatous skin cancer c)Adequately treated carcinoma in situ without evidence of disease
5.As judged by Investigator,severe or uncontrolled systemic disease (severe hepatic impairment, interstitial lung disease),unstable or uncompensated respiratory or cardiac conditions,uncontrolled hypertension,hist of or active bleeding diatheses,uncontrolled active systemic infection or IV anti infective treatment within two weeks before first dose of study drug
6.Known hist of infection with human immunodeficiency virus(HIV)
7.Serologic status reflecting active hepatitis B or C infection

Exclusion criteria related to acalabrutinib combinations (Module 1 and 2):
1.Participants must comply with Core excl. criteria
2.Current refractory nausea and vomiting, malabsorption syndrome,disease significantly affecting gastrointestinal function,stomach resection,extensive small bowel resection that is likely to affect absorption,symptomatic inflammatory bowel disease,bowel obstruction,or gastric restrictions and bariatric surgery
3.Prior use of standard anti-lymphoma therapy or radiation therapy within 14 days of receiving the first dose of study treatment
4.Requires treatment with strong CYP3A inhibitors or inducers
5.Requires treatment with proton-pump inhibitors Participants who switch from proton-pump inhibitors to H2-receptor antagonists or antacids are eligible
6.Active Cytomegalovirus(CMV)infection (positive CMV immunoglobulin M[IgM] and positive PCR result)
7.Requires or receiving therapeutic anticoagulants, with the exception of short-acting heparins, within 7 days of first dose of study treatment.Novel oral anticoagulants are allowed except for the initial high dose treatment period
8.Participants on dual antiplatelet and anticoagulant therapy(eg,aspirin and therapeutic doses of low molecular weight heparin)
9.Requires or receiving anticoagulation with vitK antagonists
10.Hist of or ongoing confirmed progressive multifocal leukoencephalopathy(PML)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified