Phase II Study of "VIPER" Chemotherapy in Rel/Ref DLBCL
Primary Purpose
Non-Hodgkin's Lymphoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bortezomib, dexamethasone, ifosfamide
mesna, cisplatin, etoposide, rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Non-Hodgkin's Lymphoma focused on measuring diffuse large b cell
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed diagnosis of CD20 positive, diffuse large B-cell NHL; de novo or transformed histologies are acceptable
- Patient must have relapsed after or not responded to at least one standard, upfront multi-agent chemotherapy for DLBCL
- Measurable PET positive disease, as defined by tumor mass > 1.5 cm in one dimension
- Stage II, III, or IV disease
- Age > 18 years
- Adequate liver and kidney function (total bilirubin < 2 x ULN and creatinine < 2.0 mg/dl, unless abnormalities are related to lymphoma or Gilbert's disease
- Adequate bone marrow reserves (absolute neutrophil count >1500 cells/mm3 and platelet count > 100,000, unless cytopenias are the result of marrow infiltration by lymphoma
- ECOG performance status < 2
- Life expectancy of at least 3 months
- Bortezomib-naive
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- Male subject agrees to use an acceptable method for contraception for the duration of the study.
Exclusion Criteria:
- Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- Patient has hypersensitivity to boron or mannitol
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. (Pregnancy testing is not required for post-menopausal or surgically sterilized women)
- Patient has received other investigational drugs or cytotoxic chemotherapy within 14 days of enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study
- Known HIV infection
- Active Hepatitis B or C as defined by positive Hepatitis B surface antigen or hepatitis C RNA
- Known CNS disease
- Pregnant or nursing women
- Concurrent treatment with other chemotherapy or anti-lymphoma therapy, including corticosteroids, unless on a stable dose of corticosteroids less than the equivalent of 20 mg of prednisone each day for treatment of disease not related to lymphoma
- Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
- Any condition that, in the opinion of the investigator, would prevent the subject from being fully compliant with the protocol.
Sites / Locations
- Weill Cornell Medical College
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Study Treatment
Arm Description
This is a single arm study
Outcomes
Primary Outcome Measures
Complete Response
Complete Response
Secondary Outcome Measures
Full Information
NCT ID
NCT00504751
First Posted
July 19, 2007
Last Updated
February 23, 2017
Sponsor
Weill Medical College of Cornell University
Collaborators
Millennium Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00504751
Brief Title
Phase II Study of "VIPER" Chemotherapy in Rel/Ref DLBCL
Official Title
Phase II Trial of "VIPER" Chemotherapy in Relapsed and Refractory Diffuse Large B-cell Lymphoma (NHL)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
May 2007 (Actual)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
February 17, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University
Collaborators
Millennium Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Objectives
The primary objective of this study is to:
• determine the complete and partial response rates and the toxicity profile of bortezomib (VELCADE, formerly PS-341) when administered in combination with DICE chemotherapy plus rituximab (i.e. VIPER) to patients with relapsed or refractory diffuse large B-cell non-Hodgkin's lymphoma
The secondary objectives of this study are to:
assess event free survival and overall survival
assess conversion of chemo-resistant to chemo-sensitive disease
assess the ability to collect stem cells from patients treated with salvage VIPER who then undergo autologous stem cell transplantation
perform correlative studies on pre-treatment tumor biopsy specimens; analyses will include the assessment of immunohistochemical expression patterns (germinal center B cell vs. activated B cell) and NF-κB activity
Detailed Description
Single arm phase II trial of combination therapy bortezomib, DICE, and Rituximab in patients with relapsed and refractory diffuse large B-cell non-Hodgkin's lymphoma (NHL)
VIPER chemotherapy will be administered every 28 days at the following doses:
Dexamethasone 40 mg IV days 1-4
Ifosfamide 1.0 gram/m2 CIVI over 24 hours days 1-4
Mesna 1.0 gram/m2 CIVI over 24 hours days 1-4 (mix solution with ifosfamide)
Cisplatin 25 mg IV days 1-4
Etoposide 100 mg/m2 CIVI over 24 hours days 1-4
Rituximab 500 mg/m2 IV day 1 prior to start of DICE (375 mg/m2 for subsequent cycles)
VELCADE 1.5 mg/m2 on days 2 and 5
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma
Keywords
diffuse large b cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Study Treatment
Arm Type
Experimental
Arm Description
This is a single arm study
Intervention Type
Drug
Intervention Name(s)
bortezomib, dexamethasone, ifosfamide
Intervention Description
VIPER chemotherapy will be administered every 28 days at the following doses:
Dexamethasone 40 mg IV days 1-4
Ifosfamide 1.0 gram/m2 CIVI over 24 hours days 1-4
Mesna 1.0 gram/m2 CIVI over 24 hours days 1-4 (mix solution with ifosfamide)
Cisplatin 25 mg IV days 1-4
Etoposide 100 mg/m2 CIVI over 24 hours days 1-4
Rituximab 500 mg/m2 IV day 1 prior to start of DICE (375 mg/m2 for subsequent cycles)
VELCADE 1.5 mg/m2 on days 2 and 5
Intervention Type
Drug
Intervention Name(s)
mesna, cisplatin, etoposide, rituximab
Intervention Description
VIPER chemotherapy will be administered every 28 days at the following doses:
Dexamethasone 40 mg IV days 1-4
Ifosfamide 1.0 gram/m2 CIVI over 24 hours days 1-4
Mesna 1.0 gram/m2 CIVI over 24 hours days 1-4 (mix solution with ifosfamide)
Cisplatin 25 mg IV days 1-4
Etoposide 100 mg/m2 CIVI over 24 hours days 1-4
Rituximab 500 mg/m2 IV day 1 prior to start of DICE (375 mg/m2 for subsequent cycles)
VELCADE 1.5 mg/m2 on days 2 and 5
Primary Outcome Measure Information:
Title
Complete Response
Description
Complete Response
Time Frame
26 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed diagnosis of CD20 positive, diffuse large B-cell NHL; de novo or transformed histologies are acceptable
Patient must have relapsed after or not responded to at least one standard, upfront multi-agent chemotherapy for DLBCL
Measurable PET positive disease, as defined by tumor mass > 1.5 cm in one dimension
Stage II, III, or IV disease
Age > 18 years
Adequate liver and kidney function (total bilirubin < 2 x ULN and creatinine < 2.0 mg/dl, unless abnormalities are related to lymphoma or Gilbert's disease
Adequate bone marrow reserves (absolute neutrophil count >1500 cells/mm3 and platelet count > 100,000, unless cytopenias are the result of marrow infiltration by lymphoma
ECOG performance status < 2
Life expectancy of at least 3 months
Bortezomib-naive
Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
Male subject agrees to use an acceptable method for contraception for the duration of the study.
Exclusion Criteria:
Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment.
Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
Patient has hypersensitivity to boron or mannitol
Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. (Pregnancy testing is not required for post-menopausal or surgically sterilized women)
Patient has received other investigational drugs or cytotoxic chemotherapy within 14 days of enrollment
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Known HIV infection
Active Hepatitis B or C as defined by positive Hepatitis B surface antigen or hepatitis C RNA
Known CNS disease
Pregnant or nursing women
Concurrent treatment with other chemotherapy or anti-lymphoma therapy, including corticosteroids, unless on a stable dose of corticosteroids less than the equivalent of 20 mg of prednisone each day for treatment of disease not related to lymphoma
Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
Any condition that, in the opinion of the investigator, would prevent the subject from being fully compliant with the protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Furman, MD
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Phase II Study of "VIPER" Chemotherapy in Rel/Ref DLBCL
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