Status and phase
Conditions
Treatments
About
The purpose of this study is to is to determine the effects (good and bad) of Zanubrutinib in Combination with Pola-R-CHP and High-dose Methotrexate in patients with Secondary Central Nervous System (CNS) Lymphoma.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Men and women ≥ 18 years of age on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place).
Patients must have histologic confirmation of large B-cell lymphoma (LBCL) defined by the World Health Organization (WHO) classification. All LBCL subtypes are acceptable. Note: Patients with prior treatment for indolent lymphoma are still eligible for participation as long as they did not receive anthracycline-based therapy.
Baseline 18-fluorodeoxyglucose (FDG)-positron emission tomography scan/computed tomography (PET/CT) must demonstrate FDG avid lesions compatible with CT-defined anatomical tumor sites (Note: FDG-PET/CT is not mandatory, and patients with CT scans only will be eligible for study entry as well). Patients should have at least 1 measurable site of disease per Lugano classification in FDG-PET/CT or CT scans.
Presence of systemic and CNS involvement (brain, cerebellum, brainstem, meninges, cranial nerves, eyes, spinal cord, or a combination of these) at presentation.
Determination of CNS involvement can be by brain biopsy, cerebrospinal fluid (CSF) evaluation by cytology and/or flow cytometry, neuroimaging, or strong clinical suspicion by Investigator for which CNS targeted therapy is recommended (ie, numb chin syndrome in patients with high CNS involvement risk).
Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2, except due to lymphoma involvement.
Life expectancy of greater than ≥ 3 months.
Women should avoid becoming pregnant while taking zanubrutinib and for up to 90 days after ending treatment. Therefore, women of childbearing potential must use highly effective contraceptive measures while taking zanubrutininb and for up to 90 days after stopping treatment. It is currently unknown whether zanubrutinib may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should add a barrier method. Pregnancy testing is recommended for women of reproductive potential prior to initiating therapy.
Agreement to use contraception during study participation.
Male patients with a female partner of childbearing potential are eligible if they abstained, are vasectomized or if they agree to the use of barrier contraception with other methods described above during the study treatment period and for 90 days after the last dose of zanubrutinib.
Patients must have normal organ and marrow function as defined below:
Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments (SoA).
Exclusion criteria
Primary CNS lymphoma without evidence of systemic lymphoma.
Prior systemic lymphoma therapy (Note: 1 cycle of an anthracycline based regimen, such as rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP), polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP), dose-adjusted etoposide phosphate, prednisone, oncovin, cyclophosphamide, hydroxydaunorubicin, and rituximab (EPOCH-R), or rituximab, cyclophosphamide, vincristine, doxorubicin, and methotrexate (R-Codox-M), and/or 1 dose of intrathecal therapy, will be allowed before enrollment [Section 5.9]). Note: Patients with prior treatment for indolent lymphoma are still eligible for participation as long as they did not receive anthracycline-based therapy.
Any uncontrolled or clinically significant cardiovascular disease including the following:
Active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia (eg, idiopathic thrombocytopenia purpura).
Uncontrolled intercurrent illness such as liver cirrhosis, autoimmune disorder requiring immunosuppression or long-term corticosteroids (> 10 mg daily prednisone equivalent), or any other serious medical condition, laboratory abnormality, or psychiatric illness which would compromise ability to comply with study procedures.
Severe or debilitating pulmonary disease.
Concurrent malignancy requiring active therapy.
Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer.
Active fungal, bacterial and/or viral infection requiring systemic therapy.
Breastfeeding or pregnant women.
Known active infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows:
Patients with impaired decision-making capacity.
Ongoing treatment with medications that are strong cytochrome P450 (CYP), family 3, subfamily A (CYP3A) inducers.
Underlying medical conditions that, in the Investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs.
Unable to swallow capsules or disease significantly affecting gastrointestinal function, such as malabsorption syndrome, stomach or small bowel resection, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
History of severe bleeding disorder, such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention.
History of stroke or intracranial hemorrhage within 180 days before the first dose of zanubrutinib.
Major surgery within 4 weeks of the first dose of zanubrutinib. Major surgery is defined as open-heart, reconstructive, transplant, removal of a brain tumor or a damaged kidney surgery.
The patient requires treatment with warfarin, warfarin derivatives, or other vitamin K antagonists.
Vaccination or requirement for vaccination with a live vaccine within 28 days prior to the first dose of study drug or at any time during planned study treatment.
Hypersensitivity to zanubrutinib, any components of pola-R-CHP, regimen, and/or high-dose (HD) methotrexate (MTX), or any of the other ingredients of the applicable study medications.
Concurrent participation in another therapeutic clinical trial.
Primary purpose
Allocation
Interventional model
Masking
20 participants in 1 patient group
Loading...
Central trial contact
Juan P Alderuccio, MD
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal