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).
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
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
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.
Azienda Ospedaliera SS. Antonio e Biagio e C. Arrigo
Alessandria, Italy
Istituto di Ematologia ed Oncologia Medica A. Seragnoli Policlinico S. Orsola
Bologna, Italy
Spedali Civili
Brescia, Italy
Ematologia I, A.O.U. San Martino
Genova, Italy
Ospedale Umberto I - DH Oncoematologico
Nocera Inferiore, Italy
Divisione di Ematologia Università Avogadro
Novara, Italy
AO Ospedali Riuniti Villa Sofia-Cervello
Palermo, Italy
A.O. Città della Salute e della Scienza (Ematologia Univ)
Torino, Italy
A.O. Città della salute e della scienza (S.C. Ematologia)
Torino, Italy
AO Universitaria di Udine
Udine, Italy
Overall Response Rate (ORR) at the End of the Induction Phase
ORR is defined as the proportion of patients achieving a Complete Response (CR) or Partial Response (PR) according to the Cheson 1999 response criteria
Time frame: 6 months
Complete Response (CR) Rate
Proportion of CR at the end of the induction phase according to the Cheson 1999 response criteria
Time frame: 6 months
Time to Response (TTR)
TTR is defined as the time from enrolment to Overall Response
Time frame: 36 months
Progression Free Survival (PFS)
PFS is defined as the time from enrolment to disease progression or relapse or death from any cause
Time frame: 36 months
Overall Survival (OS)
OS is defined as the time from enrolment to death from any case
Time frame: 36 months
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