A Phase II Study of IGEV +/- Bortezomib Before Hign Dose Consolidation in Relapsed/Refractory Hodgkin's Lymphoma

Sponsor

Istituto Clinico Humanitas (Other)

Overall Status

Completed

CT.gov ID

NCT00636311

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate if the addition of Bortezomib (Velcade) to IGEV combination (Ifosfamide, Gemcitabine and Vinorelbine) in patients with relapsed/refractory Hodgkin's lymphoma increases the rate of complete remission (PET negativity) at transplantation.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin Disease	Drug: Ifosfamide, Gemcitabine, Vinorelbine Drug: Bortezomib + IGEV	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

IGEV +/- Bortezomib (Velcade) as Induction Before High Dose Consolidation in Relapsed/Refractory Hodgkin's Lymphoma After First Line Treatment: a Randomized Phase II Trial. On Behalf of Intergruppo Italiano Linfomi

Study Start Date :

Feb 1, 2008

Actual Primary Completion Date :

Apr 1, 2008

Actual Study Completion Date :

Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 IGEV regimen (Ifosfamide, Gemcitabine, Vinorelbine)	Drug: Ifosfamide, Gemcitabine, Vinorelbine Ifosfamide 2000 mg/sqm, day 1-4 (plus MESNA); Gemcitabine 800 mg/sqm, day 1 and 4; Vinorelbine 20 mg/sqm, day 1; Prednisone 100 mg, day 1-4; G-CSF 1 vial sc, day 7-12 of each 21-day course.
Experimental: 2 B-IGEV (Bortezomib + IGEV)	Drug: Bortezomib + IGEV Bortezomib 1,3 mg/sqm, day 1, 4, 8; Ifosfamide 2000 mg/sqm, day 1-4 (plus MESNA); Gemcitabine 800 mg/sqm, day 1 and 4; Vinorelbine 20 mg/sqm, day 1; Prednisone 100 mg, day 1-4; G-CSF 1 vial sc, day 7-12 of each 21-day course.

Arm

Intervention/Treatment

Active Comparator: 1

IGEV regimen (Ifosfamide, Gemcitabine, Vinorelbine)

Drug: Ifosfamide, Gemcitabine, Vinorelbine

Ifosfamide 2000 mg/sqm, day 1-4 (plus MESNA); Gemcitabine 800 mg/sqm, day 1 and 4; Vinorelbine 20 mg/sqm, day 1; Prednisone 100 mg, day 1-4; G-CSF 1 vial sc, day 7-12 of each 21-day course.

Experimental: 2

B-IGEV (Bortezomib + IGEV)

Drug: Bortezomib + IGEV

Bortezomib 1,3 mg/sqm, day 1, 4, 8; Ifosfamide 2000 mg/sqm, day 1-4 (plus MESNA); Gemcitabine 800 mg/sqm, day 1 and 4; Vinorelbine 20 mg/sqm, day 1; Prednisone 100 mg, day 1-4; G-CSF 1 vial sc, day 7-12 of each 21-day course.

Outcome Measures

Primary Outcome Measures

PET negativity rate obtained with IGEV or B-IGEV will be compared [PET negativity after 4 courses of induction (IGEV or B-IGEV)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of Hodgkin's lymphoma failing or relapsing after first-line chemotherapy (MOPP/AVBD , MOPP/EBV/CAD and analogs are considered one line)
Age >18 and <65 years
Signed informed consent
If female, patient is either postmenopausal or surgically sterilized or willing to use an acceptable method of birth control
If male, patient agrees to use an acceptable barrier method for contraception
ECOG performance status <2
Platelet count >100.000/mmc
Hemoglobin >7.5 g/dL
Absolute neutrophil count (ANC) >1.500/mmc
Serum calcium <3.5 mmol/L (<14 mg/dL)
AST/ALT: <2.5 x the ULN
Total bilirubin: <1.5 x the ULN

Exclusion Criteria:

Previous treatment with velcade
Nitrosoureas within 6 weeks or any other chemotherapy within 3 weeks before enrollment
Immunotherapy or antibody therapy within 4 weeks before enrollment
Experimental drug or medical device within 4 weeks before start of treatment
Major surgery within 4 weeks before enrollment
History of allergic reaction attributable to compounds containing boron or mannitol or any of the drugs in the IGEV regimen
Peripheral neuropathy of NCI CTCAE Grade 2 or higher
Myocardial infarction within 6 months of enrollment or NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances including diabetes mellitus
Need for therapy with concomitant CYP 3A4 inhibitors or inducers
HIV-positive, if known
Hepatitis B surface antigen-positive or active hepatitis C infection, if known
Active systemic infection requiring treatment
If female, pregnancy or breast-feeding.