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

January 28, 2014 updated by: Armando Santoro, MD

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 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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • MI
      • Rozzano, MI, Italy, 20089
        • Recruiting
        • Istituto Clinico Humanitas
        • Principal Investigator:
          • Armando Santoro, MD
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Rita Mazza, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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.
Time Frame: 3 weeks
3 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DLT
Time Frame: 3 weeks
Incidence of dose limiting toxicities (DLTs)
3 weeks
safety profile
Time Frame: 3 months
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
Time Frame: 3 months
3 months
hematologic toxicity
Time Frame: 3 months
Assessment of neutropenia and thrombocytopenia incidence, duration, as well as platelet transfusion requirement
3 months
CD34+ cells count
Time Frame: 3 months
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
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Armando Santoro, MD

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2011

Primary Completion (Anticipated)

March 1, 2014

Study Completion (Anticipated)

December 1, 2015

Study Registration Dates

First Submitted

May 27, 2013

First Submitted That Met QC Criteria

June 20, 2013

First Posted (Estimate)

June 24, 2013

Study Record Updates

Last Update Posted (Estimate)

January 29, 2014

Last Update Submitted That Met QC Criteria

January 28, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ONC-2010-003
  • 2010-022452-23 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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