Phase 1 Study of Ibrutinib and Immuno-Chemotherapy Using Temozolomide, Etoposide, Doxil, Dexameth… (NCT02203526) | Clinical Trial Compass
Active — Not RecruitingPhase 1
Phase 1 Study of Ibrutinib and Immuno-Chemotherapy Using Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib,Rituximab (TEDDI-R) in Primary CNS Lymphoma
United States68 participantsStarted 2014-08-14
Plain-language summary
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.
Who can participate
Age range
18 Years – 120 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
* ELIGIBILITY CRITERIA:
* Patients must have histologically or cytologically confirmed primary central nervous system diffuse large B-cell lymphoma. Patients with PCNSL that is only extracranial will not be eligible. Patients with relapsed or refractory disease, as well as untreated patients,
are eligible. Untreated patients must not have high dose chemotherapy and autologous stem cell transplantation (ASCT) planned as part of frontline therapy to be eligible for the trial.
* At least 2 weeks have passed since prior chemotherapy, biological therapy, radiation therapy, other investigational or anti-cancer therapy that is considered disease-directed.
* Ibrutinib must be discontinued 7 days before (when possible) until 7 days after major surgery, and 3 days before (when possible) until 3 days after minor surgery. Thus, patients to be enrolled on an ibrutinib trial must have completed major surgery \>= 7 days before initiating treatment, and/or must have completed minor surgery \>= 3 days before initiating treatment.
* Recovered from prior toxicities to Grade 0-1 at least 2 weeks prior to investigational therapy.
* Age \>=18 years. Because no dosing or adverse event data are currently available on the use of ibrutinib and TEDDI-R in patients \<18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.
* ECOG performance status \<=2 (Karnofsky \>=60%) unless due to neurologic deficits caused by CNS lymphoma with the following excepti…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
safety and feasibility in untreated PCNSL patients
Timeframe: Initiation of ibrutinib until 30 days after treatment
2
MTD of ibrutinib with anti-fungal prophylaxis when given with TEDD-R
Timeframe: after one cycle
3
MTD of ibrutinib when given with TEDD-R
Timeframe: after one cycle
4
Complete Response rate in untreated PCNSL patients
Timeframe: every 3 months for 1 year, every 4 months year 2, every 6 months year 3 then yearly