Linfoma de Hodgkin clásico refractario/en recaída MedDRA version: 9.1 Level: LLT Classification code 10020328 Term: Hodgkin's lymphoma
Conditions
Interventions
Product Name: panobinostat
Product Code: LBH589E
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: panobinostat
CAS Number: 404950-80-7
Current Sponsor code: LBH589E
Concentration unit: mg milli
Sponsors
Novartis Farmacéutica S.A.
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 classical HL (i.e. Nodular sclerosing, Mixedcellularity, Lymphocyte-rich, Lymphocyte depleted) 4. Patient has progressive disease after receiving high dose chemotherapy with AHSCT. 5. Patient has progressive disease on or after therapy with a gemcitabine- or vinorelbine- or vinblastine-containing regimen, after first relapse. Note: If last therapy was more than ? 18 months ago, then a biopsy should be performed to confirm diagnosis. 6. Patient has at least one site of measurable nodal disease at baseline ? 2.0 cm in the longest transverse diameter and clearly measurable in at least two perpendicular dimensions, as determined by CT scan (MRI is allowed only if CT scan can not be performed). See Posttext supplement 1. Note: Patients with bone marrow involvement are eligible, but this criteria alone should not be used for disease measurement. 7. 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 10 9/L [SI units 1.5 x 109/L] ? Platelet count ? 75 x 109/L ? Serum potassium, magnesium, phosphorus, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution Note: Potassium, calcium, magnesium, sodium, and/or phosphorus supplements may be given to correct values that are =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patient has a history of prior treatment with a DAC inhibitor 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 received chemotherapy or any investigational drug or undergone major surgery ? 2 weeks prior to starting study drug or whose side effects of such therapy have not resolved to ? grade 1 5. Patient has been treated with > 5 prior systemic lines of treatment (see Post-text supplement 2 for definitions and examples) 6. Patient has received prior radiation therapy ? 4 weeks or limited field radiotherapy ? 2 weeks prior to start of study treatment or whose side effects of such therapy have not resolved to ? grade 1 7. Patient is using any anti-cancer therapy concomitantly 8. Patient has been treated with allogeneic hematopoietic stem cell transplant who has received immunosuppressive therapy within 90 days prior to start of screening and/or have ? Grade 2 graft versus host disease (GvHD). 9. Patient has a history of another primary malignancy ? 3 years before study entry, with the exception of non-melanoma skin cancer, and carcinoma in situ of uterine cervix 10. Patient has a history of CNS involvement with lymphoma 11. Patient has impaired cardiac function including any of the following: ? Complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia ( 450 msec on screening ECG, or right bundle branch block + left anterior hemiblock (bifascicular block) ? Presence of unstable atrial fibrillation (ventricular heart rate >100 bpm). Patients with stable atrial fibrillation are allowed in the study provided they do not meet the other cardiac exclusion criteria ? Previous history angina pectoris or acute MI within 6 months ? Congestive heart failure (New York Heart Association functional classification III-IV) 12. Patient has any other clinically significant heart disease (e.g., uncontrolled hypertension) 13. Patient has an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or small bowel resection) 14. Patient has unresolved diarrhea ? grade 2 15. Patient has any other concurrent severe and/or uncontrolled medical condition(s) (e.g., uncontrolled diabetes mellitus, active or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnoea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with the protocol 16. Patient has a known history of HIV seropositivity (screening HIV testing is not required) 17. Patient has active bleeding diathesis or is currently being treated with therapeutic doses of sodium warfarin (Coumadin®) or other vitamin K active agents Note: mini-dose of Coumadin® (e.g., 1 mg/day) or anti-coagulant agents given to maintain intravenous line patency, as well as unfractionated or low molecular weight heparin therapy is permitted. 18. Patient is using medications that have a relative risk of prolonging the QT interval o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the objective response rate to therapy with oral panobinostat in patients with refractory/relapsed classical HL using modified response criteria for malignant lymphoma (see Post-text supplement 1).;Secondary Objective: ? To determine response rate based on central review of CT scan/MRI ? To assess the time to response ? To assess the duration of response ? To evaluate progression-free survival, PFS rate at 6 month and 8 month ? To assess the safety and tolerability of panobinostat treatment ? To assess overall survival ? To characterize the PK of panobinostat, including the parent drug and any potential metabolite/s when feasible in at least 15 consenting patients with HL;Primary end point(s): CT scan to assess the response rate and for monitoring for progression safety pharmacokinetic parameters: Cmax, Tmax, and AUC0-24 Exploratory FDG-PET scan response and exploratory biomarkers | — |
Countries
Belgium, France, Germany, Italy, Spain, United Kingdom
Outcome results
None listed