Clinical trial NCT01523834
Conditions: Diffuse Large B-cell Lymphoma
Keywords: Diffuse Large B-cell Lymphoma (DLBCL) Panobinostat Patients with relapsed/refractory DLBCL.
Sponsor: Fondazione Italiana Linfomi - ETS
Start date: 2011-02-01; Completion date: 2017-04-01
Enrollment: 35 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Treatment of adult patients with Diffuse Large B-cell Lymphoma (DLBCL), relapsed or refractory to previous CHOP-R (or CHOP-R like regimen) front line therapy, relapsed or refractory to second or subsequent salvage therapies which included high dose therapy with autologous stem cell support (ASCT).

Treatment of adult patients with DLBCL relapsed or refractory to front line therapy with CHOP-R (or CHOP-R like regimen) or subsequent treatments, who are not consider eligible for ASCT consolidation because of age, co-morbidities, impossibility to perform ASCT.

The trial is conducted according to the optimal two-stage design of Simon with alpha 0.05 and beta 0.10, considering the following two hypotheses: first a response rate (RR) less than 10% is of no further interest; and second, an RR 30% is clinically meaningful. In the initial stage, 18 patients have to enter onto the study. If less than 3 responses (\</=2 in 18) will be observed, the trial would be terminated. Otherwise, accrual will continue to a total of a maximum of 35 patients. At the end of the trial, if 6 or fewer responses will occur among the 35 patients (\</= 6 in 35), it will be concluded that the regimen is not worthy of further investigations for that group of patients.

The treatment is divided in three phases: induction phase (course 1 to 6), consolidation phase (courses 7 to 12), maintenance phase (from course 13 until the end of therapy for any reason).

Detailed description:
Overview Of Study Design This is a prospective, multicenter phase II trial designed to evaluate the safety and activity of the panobinostat in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Study design The trial is conducted according to the optimal two-stage design of Simon with alpha 0.05 and beta 0.10, considering the following two hypotheses: first a response rate (RR) less than 10% is of no further interest; and second, an RR 30% is clinically meaningful. In the initial stage, 18 patients have to enter onto the study. If less than 3 responses (£ 2 in 18) will be observed, the trial would be terminated. Otherwise, accrual will continue to a total of a maximum of 35 patients. At the end of the trial, if 6 or fewer responses will occur among the 35 patients (£ 6 in 35), it will be concluded that the regimen is not worthy of further investigations for that group of patients. The treatment is divided in three phases: induction phase (course 1 to 6), consolidation phase (courses 7 to 12), maintenance phase (from course 13 until the end of therapy for any reason). Study duration This study is expected to start in February 2011. The last patient is expected to be enrolled at the end of January 2013. Considering a possible treatment duration of 24 months, this trial is due to be completed by January 2015.

Objectives:

Primary objective 1. To explore the antitumor activity of panobinostat in term of overall response (OR) at the end of the induction phase (i.e. month 6 from the beginning of panobinostat) Secondary objectives

1. To explore the antitumor activity of panobinostat in terms of Complete Response (CR)
2. To assess the time to response (TTR)
3. To evaluate Progression Free Survival (PFS)
4. To assess the safety and tolerability of panobinostat
5. To evaluate the Overall Survival (OS) Exploratory objectives

1\. To study the impact of pharmacogenetics in predicting the response to panobinostat 2. To study the impact of immunohistochemical patterns and patient's specific gene expression and response to panobinostat 3. To assess the correlation between "telomeric asset" and response to panobinostat

Arms: arm 1: The treatment is divided in three phases: induction phase (course 1 to 6), consolidation phase (courses 7 to 12), maintenance phase (from course 13 until the end of therapy for any reason). The duration of a treatment course will be 28 days. The first dose of panobinostat in course 1 defines day 1 of the treatment cycle, and each cycle thereafter will begin 28 days later.

Treatment:

Panobinostat should be taken p.o. at the dose of 40 mg/day three-times every week (QW) (e.g., on Monday, Wednesday, and Friday or Tuesday, Thursday, and Saturday), as part of a 4 week (28 days) treatment cycle.
Interventions: intervention 1: Panobinostat
Intervention descriptions: intervention 1: Induction Phase: Patients will receive panobinostat for 6 courses (1 course = 28 days). Consolidation phase (courses 7-12). Maintenance phase (course 13-end of therapy).

Panobinostat should be taken p.o. at the dose of 40 mg/day 3-times every week (QW) as part of a 4 week treatment cycle. The dose of panobinostat may be modified: the 1st dose adjustment consists in the modification of drug administration from 3 times every week (QW) to 3 times every other week (QOW). Levels lower than 30 mg 3 times QOW is not permitted.

Protocol documents: