A study to assess AZD4573 in novel combination with acalabrutinib in participants with relapsed or refractory diffuse large B-cell lymphoma or relapsed or refractory marginal zone lymphoma

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-IT
• Lead Sponsor: ASTRAZENECA AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-11-08
• Last Update Posted: 8 January 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

Patients must meet all the inclusion criteria of both the core and module protocol.
Core
1.Patients 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.Documented active disease requiring treatment that is relapsed or refractory defined as:
a.Recurrence of disease after response to at least one prior line(s) of therapy,or
b.Progressive disease after completion of or on the treatment regimen preceding entry into the study or
c. Disease that did not achieve an objective response (CR or PR).
4. Adequate organ function at screening as defined in the protocol
5. Uric acid level < upper limit of normal (ULN). If hyperuricaemia is present at screening, SoC therapy for hyperuricaemia should be administered (including IV fluid and rasburicase or allopurinol) to reduce the uric acid levels to < ULN before the start of study intervention.

Module 1
1.Patients must comply with the eligibility criteria described in Core module
2. Patients with histologically confirmed r/r DLBCL or r/r MZL, for whom a clinical study is the best option (in the opinion of the investigator) for next treatment based on response and/or tolerability to prior lines of therapy.

PLEASE REFER TO THE PROTOCOL FOR FUTHER INCLUSION CRITERIA
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 47
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 31

Exclusion Criteria

1. Patients with non-secretory myeloma
2. Except alopecia, and neutropenia, unresolved non-haematological toxicities from prior therapy >CTCAE Grade 1 at study treatment start
3. Presence or history 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, history 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 history of infection with human immunodeficiency virus (HIV).
7. Serologic status reflecting active hepatitis B or C infection:
(a) Hepatitis B core antibody (anti-HBc) positive, surface antigen negative patients must have a negative polymerase chain reaction (PCR) result before enrolment. Hepatitis B surface antigen positive or hepatitis B PCR positive patients are excluded. (b) Hepatitis C antibody positive
patients must have a negative PCR result before enrolment. Hepatitis C PCR positive patients are excluded.
8. Any of the following cardiac criteria:
(a) Resting QT interval corrected using Fridericia's formula (QTcF) >= 470 msec on a single ECG.
(b) Any clinically important abnormalities in rhythm (excepting patients with a pacemaker), conduction or morphology of resting ECG.
(c) Factors elevating the risk of QTc prolongation or arrhythmic events such as congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age.
Concomitant medications known to prolong QTc should be used with caution and cannot be used starting with the first dose of study drug and through the DLT assessment period (Part A) or during ECG assessments.

PLEASE REFERO TO THE PROTOCOL FOR FURTHER EXCLUSION CRITERIA

Study & Design

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