Patient has a history of DLBCL according to the WHO classification. with progressive disease after receiving at least CHOP-R or CHOP-R like first line regimen and is not considered eligible for intensive MedDRA version: 13.1 Level: HLGT Classification code 10025320 Term: Lymphomas non-Hodgkin's B-cell System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: PANOBINOSTA
Product Code: LBH589
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PANOBINOSTAT
CAS Number: 404950-80-7
Current Sponsor code: LBH589
Concentration unit: mg milligra
Sponsors
FONDAZIONE ITALIANA LINFOMI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient age is = 18 years 2. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of = 2 3. Patient has a history of DLBCL according to the WHO classification 4. Patient has progressive disease after receiving at least CHOP-R or CHOP-R like first line regimen, standard second line therapy (DHAP, ESHAP, ICE or similar salvage regimens) inclusive ASCT 5. Patient has progressive disease after receiving at least CHOP-R or CHOP-R like first line regimen and is not considered eligible for intensive salvage therapy including ASCT because of age, co-morbidities, impossibility to perform ASCT 6. Patient undergoes at baseline new lymphnode or other pathologic tissue biopsy for confirmation of diagnosis and biologic studies; bone marrow biopsy is not adequate for this purpose and should be performed only for staging. Patients with primary refractoriness, not eligible for intensive salvage therapy including ASCT, who performed a previous biopsy with stored frozen material 6 months or less before enrolment into the study do not have to repeat a new biopsy 7. Patient has at least one site of measurable nodal disease at baseline = 2.0 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan can not be performed). Note: Patients with bone marrow involvement are eligible, but this criteria alone should not be used for disease measurement 8. Patient has the following laboratory values (labs may be repeated, if needed, to obtain acceptable values before screen fail): • Absolute neutrophil count (ANC) = 1.5 x 109/L [SI units 1.5 x 109/L] • Platelet count = 100 x 109/L • Serum potassium, magnesium, phosphorus, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution • Serum creatinine = 1.5 x ULN • Serum bilirubin = 1.5 x ULN (or = 3.0 x ULN, if patient has Gilbert syndrome) • AST/SGOT and/or ALT/SGPT = 2.5 x upper limit of normal (ULN) or = 5.0 x ULN if the transaminase elevation is due to disease involvement 9. Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism 10. Written informed consent was obtained from the patient prior to any study-specific screening procedures 11. Patient has the ability to swallow capsules or tablets 12. Practice acceptable birth control Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patient age is = 18 years 2. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of = 2 3. Patient has a history of DLBCL according to the WHO classification 4. Patient has progressive disease after receiving at least CHOP-R or CHOP-R like first line regimen, standard second line therapy (DHAP, ESHAP, ICE or similar salvage regimens) inclusive ASCT 5. Patient has progressive disease after receiving at least CHOP-R or CHOP-R like first line regimen and is not considered eligible for intensive salvage therapy including ASCT because of age, co-morbidities, impossibility to perform ASCT 6. Patient undergoes at baseline new lymphnode or other pathologic tissue biopsy for confirmation of diagnosis and biologic studies; bone marrow biopsy is not adequate for this purpose and should be performed only for staging. Patients with primary refractoriness, not eligible for intensive salvage therapy including ASCT, who performed a previous biopsy with stored frozen material 6 months or less before enrolment into the study do not have to repeat a new biopsy 7. Patient has at least one site of measurable nodal disease at baseline = 2.0 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan can not be performed). Note: Patients with bone marrow involvement are eligible, but this criteria alone should not be used for disease measurement 8. Patient has the following laboratory values (labs may be repeated, if needed, to obtain acceptable values before screen fail): • Absolute neutrophil count (ANC) = 1.5 x 109/L [SI units 1.5 x 109/L] • Platelet count = 100 x 109/L • Serum potassium, magnesium, phosphorus, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution • Serum creatinine = 1.5 x ULN • Serum bilirubin = 1.5 x ULN (or = 3.0 x ULN, if patient has Gilbert syndrome) • AST/SGOT and/or ALT/SGPT = 2.5 x upper limit of normal (ULN) or = 5.0 x ULN if the transaminase elevation is due to disease involvement 9. Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism 10. Written informed consent was obtained from the patient prior to any study-specific screening procedures 11. Patient has the ability to swallow capsules or tablets 12. Practice acceptable birth control Exclusion criteria 1. Patient has a history of prior treatment with a DAC inhibitors including panobinostat 2. Patient will need valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat treatment 3. Patient has been treated with monoclonal antibody therapy (e.g., rituximab or anti CD-30 antibody, etc.) within 4 weeks of start of study treatment 4. Patient has been treated with any other anti lymphoma therapy within 3 weeks of start of study treatment 5. Patient is using any anti-cancer therapy concomitantly 6. Patient has been treated with > 5 prior systemic lines of treatment 7. Patient has received prior radiation therapy = 4 weeks or limited field radiotherapy = 2 weeks prior to start of study treatment 8. Patient treated with allogeneic hematopoietic stem cell transplant with active progressive cGVHD; patient has received DLI = 6 weeks prior to start of study treatment; patient is planned to receive DLI 9. Patient has a history of another malignancy = 3 years before study entry, with the exception of non-melanoma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: 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);Primary end point(s): OR | — |
Countries
Italy
Outcome results
None listed