A Modular Phase I/II, Open-label, Multicentre Study to Assess AZD4573 in Novel Combinations With Anti-cancer Agents in Patients With Advanced Haematological Malignancies
Professor Chan Cheah
- Diffuse Large B-Cell Lymphoma (DLBCL)
- Germinal Centre B-Cell DLBCL
- Non-GCB DLBCL
This trial is for previously treated patients with Diffuse Large B-Cell Lymphoma that has returned or not responded to previous treatment. Patients will receive a combination of the study drug AZD4573 and acalabrutinib. AZD4573 is a highly selective CDK9 inhibitor that induces causes lymphoma cells to die and is given intravenously. Acalabrutinib is a tablet taken by mouth and causes lymphoma cell death by blocking the BTK protein. Patients will continue to receive treatment unless they experience unacceptable side effects or it no longer works.
- Participant must be ≥ 18 years of age at the time of signing the informed consent.
- Participants with histologically confirmed, relapsed or refractory DLBCL, and where in the opinion of the investigator, a clinical trial is the best option for next treatment based on response and/or tolerability to prior lines of therapy. PART A
- Diagnosis must be confirmed by biopsy and be immunohistologically characterized.
- Tumour tissue must also be available for sending to AstraZeneca for central cell of origin/pathology testing. PART B
- Must have received standard of care first line therapy.
- Diagnosis must be confirmed by biopsy and be immunohistologically characterised.
- A newly obtained tumour biopsy is mandatory at screening to confirm cell of origin status and determine DLBCL subtype.
- Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy.
- Participants must have failed at least 2 prior therapies for the treatment of current disease, are not eligible for curative treatment options, and have no standard therapy available.
- Adequate haematologic function, without transfusion and growth factor support for ≥ 14 days before screening.
- Optional tumour biopsy on study: Participants are also encouraged to consent to and undergo an optional tumour biopsy at disease progression to support correlative biomarker studies.
- All participants must be willing and able to provide mandatory baseline bone marrow biopsy/aspirate.
- Treatment with prior Bruton’s tyrosine kinase inhibitor.
- Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- Prior use of standard anti-lymphoma therapy or radiation therapy within 14 days of receiving the first dose of study treatment.
- Requires treatment with strong CYP3A inhibitors or inducers.
- Requires treatment with proton-pump inhibitors. Participants receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrolment to this study.
- Serologic status reflecting active hepatitis B or C infection.
- Active Cytomegalovirus (CMV) infection.
- Receipt of live, attenuated vaccine within 28 days before the first dose of study treatment (s).
- Requires or receiving therapeutic anticoagulants, with the exception of short-acting heparins, within 7 days of first dose of study treatment.
- Participants on dual antiplatelet and therapeutic anticoagulant therapy.