A trial evaluating the effectiveness of combining standard R-CHOP treatment with acalabrutinib in patients with newly diagnosed diffuse large B-cell lymphoma
- Conditions
- Diffuse large B-cell lymphomaCancerNon-follicular (diffuse) lymphoma, unspecified
- Registration Number
- ISRCTN14251143
- Lead Sponsor
- niversity Hospital Southampton NHS Foundation Trust
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 375
Current inclusion criteria as of 30/01/2024:
1. Histologically confirmed DLBCL, expressing CD20. Sufficient diagnostic material should be available to forward to HMDS for gene expression profiling and central pathology review. The following diagnoses by 2016 WHO classification of lymphoid neoplasms may be included:
1.1. DLBCL, not otherwise specified (NOS)
1.2. T-cell/histiocyte-rich large B-cell lymphoma
1.3. Epstein-Barr virus positive DLBCL, NOS
1.4. ALK-positive large B-cell lymphoma
1.5 HHV8-positive DLBCL, NOS
1.6. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit lymphoma)
1.7. High-grade B-cell lymphoma, NOS
2. At least one bi-dimensionally measurable lesion, defined as >1.5 cm in its longest dimension.
3. Not previously treated for lymphoma and fit enough to receive combination chemoimmunotherapy with curative intent
4. Stage IAX (bulk defined as lymph node mass [either single or conglomerate] diameter >7.5cm) to stage IV disease and deemed to require a full course of chemotherapy. Patients with non-bulky IE disease will not be eligible.
5. ECOG performance status 0-2 or 3 if this is directly attributable to lymphoma.
6. Adequate bone marrow function with platelets >100x109/L; neutrophils >1.0x109/L prior to cycle 1 treatment, unless lower figures are attributable to lymphoma.
7. Measured or calculated creatinine clearance >30mls/min, (calculated using the formula of Cockcroft and Gault [(140-Age) x Mass (kg) x (1.04 (for women) or 1.23 (for men))/Serum Creatinine (µmolL)]).
8. Serum bilirubin =35µmol/L and transaminases (AST or ALT) <1.5x upper limit of normal prior to cycle 1 treatment.
9. Cardiac function sufficient to tolerate 300mg/m2 of doxorubicin. A pre-treatment echocardiogram or MUGA is required to establish baseline LVEF equal to or greater than institutional normal range.
10. No concurrent uncontrolled medical condition.
11. Life expectancy >3 months.
12. Aged 16 years or above.
13. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
14. Ability to understand the purpose and risks of the study and provide signed and dated informed consent.
Previous inclusion criteria:
1. Histologically confirmed DLBCL, expressing CD20. Sufficient diagnostic material should be available to forward to HMDS for gene expression profiling and central pathology review. The following diagnoses by 2016 WHO classification of lymphoid neoplasms may be included:
1.1. DLBCL, not otherwise specified (NOS)
1.2. T-cell/histiocyte-rich large B-cell lymphoma
1.3. Epstein-Barr virus positive DLBCL, NOS
1.4. ALK-positive large B-cell lymphoma
1.5 HHV8-positive DLBCL, NOS
1.6. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit lymphoma)
1.7. High-grade B-cell lymphoma, NOS
2. At least one bi-dimensionally measurable lesion, defined as >1.5 cm in its longest dim
Current exclusion criteria as of 30/01/2024:
1. Previous history of treated or untreated indolent lymphoma. Newly diagnosed patients with DLBCL found to have small cell infiltration of the bone marrow or other diagnostic material (discordant lymphoma) will be eligible.
2. Patients who have received immunisation with a live vaccine within four weeks prior to enrolment will be ineligible.
3. Diagnosis of primary mediastinal lymphoma.
4. Diagnosis of primary Central Nervous System lymphoma or secondary CNS involvement.
5. History of stroke or intracranial haemorrhage in preceding 6 months.
6. History of bleeding diathesis (e.g.haemophilia, von Willebrand disease).
7. History of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components).
8. Requires or receiving anticoagulation with warfarin or equivalent antagonists (e.g. phenprocoumon) within 7 days of first dose of acalabrutinib. Patients using therapeutic low molecule weight heparin or low dose aspirin will be eligible, as will those receiving direct oral anticoagulants.
9. Prior exposure to an inhibitor in the BCR pathway (e.g. Btk inhibitors, phosphoinositide-3 kinase (PI3K), or Syk inhibitors) or BCL-2 inhibitor (e.g. ABT-199).
10. Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
11. Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Patients receiving proton pump inhibitors should switch to short-acting H2-receptor antagonists or antacids prior to the
commencement of acalabrutinib, if randomised to receive acalabrutinib.
12. Active significant infection (e.g. progressive multifocal leukoencephalopathy (PML), tuberculosis, sepsis, and opportunistic infections).
13. Uncontrolled autoimmune haemolytic anaemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
14. Major surgery in the preceding 4 weeks of first dose of Acalabrutinib (if applicable).
15. Corticosteroid use >30 mg/day of prednisone or equivalent, for purposes other than for lymphoma symptom control. Patients receiving corticosteroid treatment with <30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks’ duration prior to the start of Cycle 1. If glucocorticoid treatment is urgently required for lymphoma symptom control, this may be delivered in the 28 days prior to initiating therapy, with no maximum dose.
16. Any of the following in the previous 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, NYHA Class II or greater congestive heart failure, cerebrovascular accident or transient ischemic attack.
17. Serological positivity for Hepatitis B, C, or known HIV infection.
a. Positive test results for chronic HBV infection (defined as positive HBsAg serology) will not be eligible. Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) will not be eligible. Patients who have protective titres of hepatitis B surface antibody (HBsAb) after vaccination will be eligible.
b. Patients positive for HCV
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression-free survival at 2 years measured using patient records
- Secondary Outcome Measures
Name Time Method