Study of Combination of PIGEV Before Autologous Stem Cell Transplant in Patients With Hodgkin's Lymphoma

Study Overview
=================
Brief Summary
-----------------
study to assess maximum tolerated dose (MTD), safety, tolerability and activity of IGEV (Ifosfamide, Gemcitabine,Vinorelbine, Prednisolone) + Panobinostat new combination in order to determine the recommended phase II dose

Detailed Description
-----------------
Patients will received 4 p-IGEV courses repeated every 3 weeks in the absence of unacceptable toxicity, whenever an objective response is observed at disease evaluation performed after II cycle. Eligible patients will be accrued in cohorts of 3 patients at each dose level and dose escalation will be performed following the standard 3+3 rule. Three patients will be treated for each dose-level, starting from level 1, for one cycle: if no dose-limiting toxicities (DLTs) will be recorded after the first cycle, treatment will be continued in those patients until study completion or unacceptable toxicity and three new patients will be treated at the next dose level. However, if one out of 3 patients will develop a DLT, the same dose-level will be administered to three additional patients for one cycle. If no one of those additional patients will experience a DLT, dose escalation will continue. If more than one over 3 or 6 patients will develop a DLT after the first cycle in any cohort, MTD will be reached. Six further patients will be treated at the lower dose in order to obtain more information about the optimal dose for phase II trials and to characterize pharmacokinetic profiles of this combination. If DLT will be found at level 1 (20 mg), 3 patients will be treated at dose -1 (10 mg). If no more than 1 patient experience toxicity, other 3 patients will be treated to assess more information about pharmacokinetic profiles and safety.

Official Title
-----------------
Phase I, Prospective, Open-label, Multi-centric, Dose Finding Trial of Combination of IGEV and Panobinostat Before Autologous Stem Cell Transplant in Patients With Hodgkin's Lymphoma

Conditions
-----------------
Hodgkin's Lymphoma

Intervention / Treatment
-----------------
* Drug: panobinostat
* Drug: Ifosfamide
* Drug: Gemcitabine
* Drug: Vinorelbine
* Drug: Prednisolone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of relapsed or refractory classical HL Measurable disease One or two prior systemic lines of treatment PS(ECOG) 0-2 Absence of bone marrow infiltration Adequate laboratory values for bone marrow, liver and renal functionality Exclusion Criteria: prior or concurrent treatment with a DAC inhibitor including panobinostat valproic acid therapy for any medical condition during the study or within 5 days prior to the first panobinostat treatment previous autologous hematopoietic stem cell transplant other concurrent therapy intended to treat the primary cancer including chemotherapy, investigational or biologic agents or other antitumor agents impaired cardiac function or unstable AF known history of HIV seropositivity, chronic hepatitis, or other active viral infections 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) pregnant or breast feeding women

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panobinostat + IGEV<br>Panobinostat + IGEV regimen (Ifosfamide, Gemcitabine, Vinorelbine, Prednisolone) | Drug: panobinostat<br>* Dose excalation oral panobinostat 3 days a week for a maximum of 4 cycles of three weeks duration<br>* Other names: LBH-589;Drug: Ifosfamide<br>* Ifosfamide 2000 mg/m2 on days 1 to 4 as a 2-hour infusion for a maximum of 4 cycles of three weeks duration<br>* Other names: Ifex;Drug: Gemcitabine<br>* Gemcitabine 800 mg/m2 on days 1 and 4 for a maximum of 4 cycles of three weeks duration<br>* Other names: Gemzar;Drug: Vinorelbine<br>* Vinorelbine 20 mg/m2 on day 1 for a maximum of 4 cycles of three weeks duration<br>* Other names: Navelbine;Drug: Prednisolone<br>* Prednisolone 100 mg on days 1 to 4 for a maximum of 4 cycles of three weeks duration<br>* Other names: Prelone;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) or the recommended phase II dose defined as the highest dosage cohort at which no more than one of six patients will experience a DLT in the first treatment cycle. |  | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT | Incidence of dose limiting toxicities (DLTs) | 3 weeks | 
| safety profile | Preliminary safety profile defined as Adverse Events (AEs), Serious Adverse Events ( SAEs) & Changes in Clinical Laboratory Evaluations | 3 months | 
| Complete Response and Overall Response Rate |  | 3 months | 
| hematologic toxicity | Assessment of neutropenia and thrombocytopenia incidence, duration, as well as platelet transfusion requirement | 3 months | 
| CD34+ cells count | Assessment of number of CD34+ collected and number of leukapheresis required to obtain an appropriate collection according to transplant program. | 3 months | 
| efficacy of PIGEV combination in terms of progression-free survival |  | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hodgkin, Lymphoma