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

Sponsor

Armando Santoro, MD (Other)

Overall Status

Unknown status

CT.gov ID

NCT01884428

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Hodgkin's Lymphoma	Drug: panobinostat Drug: Ifosfamide Drug: Gemcitabine Drug: Vinorelbine Drug: Prednisolone	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jul 1, 2011

Anticipated Primary Completion Date :

Mar 1, 2014

Anticipated Study Completion Date :

Dec 1, 2015

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Panobinostat + IGEV

Panobinostat + IGEV regimen (Ifosfamide, Gemcitabine, Vinorelbine, Prednisolone)

Drug: panobinostat

Dose excalation oral panobinostat 3 days a week for a maximum of 4 cycles of three weeks duration

Other Names:

LBH-589

Drug: Ifosfamide

Ifosfamide 2000 mg/m2 on days 1 to 4 as a 2-hour infusion for a maximum of 4 cycles of three weeks duration

Other Names:

Ifex

Drug: Gemcitabine

Gemcitabine 800 mg/m2 on days 1 and 4 for a maximum of 4 cycles of three weeks duration

Other Names:

Gemzar

Drug: Vinorelbine

Vinorelbine 20 mg/m2 on day 1 for a maximum of 4 cycles of three weeks duration

Other Names:

Navelbine

Drug: Prednisolone

Prednisolone 100 mg on days 1 to 4 for a maximum of 4 cycles of three weeks duration

Other Names:

Prelone

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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