Ibrutinib + Chemotherapy for CNS Lymphoma
Trial Summary
Will I have to stop taking my current medications?
The trial does not specify if you must stop taking your current medications, but it does mention that you should not have taken certain treatments like chemotherapy or radiation therapy for at least 2 weeks before starting the trial. Additionally, you cannot use strong CYP3A inhibitors or inducers within 7 days before the trial.
What data supports the effectiveness of the drug combination Ibrutinib + Chemotherapy for CNS Lymphoma?
What safety data exists for the combination of Ibrutinib and chemotherapy in treating CNS lymphoma?
The combination of Ibrutinib with chemotherapy for CNS lymphoma has been associated with significant safety concerns, including serious infections like pulmonary and cerebral aspergillosis. Additionally, other chemotherapy regimens for CNS lymphoma have shown toxicities affecting the kidneys and bone marrow, and some patients experienced severe side effects like neutropenic fever (a dangerous drop in white blood cells leading to fever), deep vein thrombosis (blood clots), and liver toxicity.13467
What makes the drug combination of Ibrutinib and chemotherapy unique for treating CNS lymphoma?
This treatment combines Ibrutinib, a drug that blocks a specific protein (Bruton tyrosine kinase) involved in cancer cell growth, with chemotherapy drugs to target CNS lymphoma. It has shown promising results in patients who cannot tolerate standard treatments, offering a new option for those with relapsed or hard-to-treat cases, although it may come with significant side effects.378910
What is the purpose of this trial?
BACKGROUND:* Primary CNS lymphoma (PCNSL) is a rare subtype of diffuse large B-cell lymphoma.* The outcome for patients with this diagnosis is significantly worse than for that of systemic DLBCL. Most treatment approaches in the past have included high dose methotrexate and radiation treatment.* Most PCNSLs appear to be of activated B-cell (ABC) origin.* Ibrutinib is an inhibitor of Bruton s tyrosine kinase (BTK) and effective for systemic DLBCL of ABC origin.* We propose doing a study in which ibrutinib is combined with a novel chemotherapy platform called dose adjusted temozolomide, etoposide, doxil, dexamethasone, ibrutinib, rituximab (TEDDI-R).OBJECTIVE:- Identify the maximum tolerated dose (MTD) of ibrutinib or the dose that achieves adequate CSF concentrations, whichever comes first, when ibrutinib is given with TEDDI-R.ELIGIBILITY:* Relapsed/refractory PCNSL.* Age greater than or equal to 18 years.* No pregnant or breast-feeding women.* Adequate organ function (defined in protocol).STUDY DESIGN:* This is a phase 1 study of 40 patients.* The study will have two components. 1. Phase 1: MTD of ibrutinib will be identified or the dose at which ibrutinib achieves a concentration of less than or equal to 100 nM in the CSF, when given in combination with TEDDI-R immuno-chemotherapy, whichever comes first. 2. Expansion cohort: Safety and tolerability of the regimen in relapsed/refractory or previously untreated PCNSL (DLBCL type) will be assessed at the final ibrutinib dose with TEDDI-R in 10 patients. Secondary objectives will be PFS and OS.
Research Team
Mark J Roschewski, M.D.
Principal Investigator
National Cancer Institute (NCI)
Eligibility Criteria
Adults diagnosed with primary central nervous system diffuse large B-cell lymphoma that has returned or resisted treatment. They must be at least 18 years old, not pregnant or breastfeeding, and have recovered from previous treatments. Participants need to have good organ function and cannot have used certain drugs recently.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Phase 1: Dose Escalation
MTD of ibrutinib will be identified or the dose at which ibrutinib achieves a concentration of less than or equal to 100 nM in the CSF, when given in combination with TEDDI-R immuno-chemotherapy, whichever comes first.
Expansion Cohort
Safety and tolerability of the regimen in relapsed/refractory or previously untreated PCNSL (DLBCL type) will be assessed at the final ibrutinib dose with TEDDI-R.
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- Dexamethasone
- Doxil
- Etoposide
- Ibrutinib
- Rituximab
- Temozolomide
Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:
- Inflammation
- Allergic reactions
- Respiratory diseases
- Skin conditions
- Eye diseases
- Immune system disorders
- Inflammatory conditions
- Allergic states
- Respiratory diseases
- Blood disorders
- Neoplastic diseases
- Nervous system disorders
- Inflammation
- Allergic reactions
- Respiratory diseases
- Skin conditions
- Eye diseases
- Inflammatory conditions
- Allergic states
- Respiratory diseases
- Blood disorders
Find a Clinic Near You
Who Is Running the Clinical Trial?
National Cancer Institute (NCI)
Lead Sponsor