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

Hodgkin's Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01884428
• Other study ID #: ONC-2010-003
• Secondary ID: 2010-022452-23
• Status: Recruiting
• Phase: Phase 1
• First received: May 27, 2013
• Last updated: January 28, 2014
• Start date: July 2011
• Est. completion date: December 2015

Study information

• Verified date: January 2014
• Source: Istituto Clinico Humanitas
• Contact: Armando Santoro, MD
• Phone: +39 (0)2 8224
• Email: armando.santoro[@]humanitas.it
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 2015
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin's Lymphoma
• Lymphoma

Intervention

Drug:
• panobinostat
Dose excalation oral panobinostat 3 days a week for a maximum of 4 cycles of three weeks duration
• 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
• Gemcitabine
Gemcitabine 800 mg/m2 on days 1 and 4 for a maximum of 4 cycles of three weeks duration
• Vinorelbine
Vinorelbine 20 mg/m2 on day 1 for a maximum of 4 cycles of three weeks duration
• Prednisolone
Prednisolone 100 mg on days 1 to 4 for a maximum of 4 cycles of three weeks duration

Locations

Country	Name	City	State
Italy	Istituto Clinico Humanitas	Rozzano	MI

Sponsors (1)

Lead Sponsor	Collaborator
Armando Santoro, MD

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	DLT	Incidence of dose limiting toxicities (DLTs)	3 weeks	Yes
Secondary	safety profile	Preliminary safety profile defined as Adverse Events (AEs), Serious Adverse Events ( SAEs) & Changes in Clinical Laboratory Evaluations	3 months	Yes
Secondary	Complete Response and Overall Response Rate		3 months	No
Secondary	hematologic toxicity	Assessment of neutropenia and thrombocytopenia incidence, duration, as well as platelet transfusion requirement	3 months	Yes
Secondary	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	No
Secondary	efficacy of PIGEV combination in terms of progression-free survival		3 years	No