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
- Conditions
- Haematological MalignanciesMedDRA 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-FR
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 78
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 haematological function (as defined in individual modules).
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.
PART A
Patients with r/r DLBCL including subtypes not otherwise specified NOS, HGBCL, PMBCL or large B-cell lymphoma transformed from indolent B-cell lymphomas (including but not limited to Richter Syndrome, transformed Follicular Lymphoma, transformed MZL), or r/r MZL:
•Diagnosis must be confirmed by biopsy and be immunohistologically characterised
•For patients with DLBCL, cell of origin subtype shall be characterised locally and tumour tissue must also be available for sending to AstraZeneca for central cell of origin/pathology testing.
All patients in Part A (dose setting) must consent to and provide archival tumour specimens, preferably in the form of a formalin fixed paraffin embedded block (tissue derived from the diagnostic tumour or a metastatic site). If this is not possible, an appropriate number of slides of freshly prepared unstained 5 micron sections from the archival tumour block may be provided. Archival tumour specimens must be obtained within 24 months before the first dose of investigational product. If archival material is unavailable or unsuitable for use, patients must consent to and undergo a tumour biopsy during the screening period. A fresh biopsy is strongly encouraged and preferred, however, a patient will be enrolled based on the prior pathology report.
PART B
Patients with r/r de novo DLBCL, GCB or non-GCB subtype:
•Must have received SOC first line therapy.
•Diagnosis must be confirmed by biopsy and cell of origin subtype characterised locally prior to enrolment and DLBCL be immunohistologically characterised.
•A newly obtained tumour biopsy is strongly encouraged and preferred at screening to confirm cell of origin status and determine DLBCL subtype. The patient will be enrolled based on a prior pathology report.
A recent biopsy that was taken as part of SoC prior to screening consent for this study is acceptable if no treatment was administered between the biopsy and the first dose of study treatment, and the biopsy was taken within 60 days prior to receiving the first dose.
3. Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (according to the Lugano criteria).
4. Patients must have failed at least 2 prior therapies for th
Core 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.
9. History of severe allergic or anaphylactic reactions to BH3 mimetics or hypersensitivity to excipients of study treatment
10. Documented confirmation and ongoing treatment of adrenal gland insufficiency or pancreatitis
11. History, within the previous 6 months, of
(a) coronary artery bypass graft; (b) angioplasty; (c) vascular Stent: a patient who has had a cardiac or arterial Stent within the preceding 6 months is not eligible for the study. A patient who has had a venous Stent within the preceding 6 months, is eligible. (d) myocardial infarction; (e) angina pectoris;
(f) congestive heart failure (New York Heart Association Class = 2);(g) ventricular arrhythmias requiring continuous therapy; (h) atrial fibrillation, judged as uncontrolled by the treating physician; (i) haemorrhagic or thrombotic stroke, including transient ischemic attacks or other CNS bleeding.
12. Receipt of live, attenuated vaccine within 28 days before the first dose of study treatment.
Module 1 Exclusion Criteria
1. Patients must comply with the exclusion criteria described Core module
2. Treatment with Prior BTK inhibitors
3. Current refractory nausea and vomiting, malab
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method