Back to resultsStudy of Standard-Dose Rituximab, Ifosfamide, Carboplatin and Etoposide (V-RICE)
Primary Purpose
Non-Hodgkin's Lymphoma, B-cell Lymphoma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Velcade (bortezomib), rituximab, ifosfamide, carboplatin, etoposide
Sponsored by
About this trial
This is an interventional treatment trial for Non-Hodgkin's Lymphoma focused on measuring V-RICE, Relapsed NHL, Primary Refractory NHL
Eligibility Criteria
Inclusion Criteria:
Aggressive B-cell non-Hodgkin lymphoma, CD-20 positive, in first relapse or refractory to first- or second-line chemotherapy (non-platinum)
- Diffuse large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma (Grade III), Transformed Follicular Lymphoma
- Prior Rituximab is allowed
- Prior radiation is allowed
- Prior autologous stem cell transplant is allowed
- Age 18-70 years
- ECOG performance status 0-2
- HIV seronegative
- No CNS involvement: CSF cytology is required for cases with bone marrow involvement, involvement of 2 or more extranodal sites, presentation in the testes or paranasal sinuses, or if any clinical suspicion of CNS involvement (e.g., cranial nerve deficits)
- Measurable disease on CT scan by international working group response criteria • 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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, intra-uterine 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:
- Subject has a platelet count of less than 75,000.
- Subject has an absolute neutrophil count of less than 1000
- Subject has a calculated or measured creatinine clearance of <60 mL/minute within 14 days before enrollment.
- Subject has grade 2 or greater peripheral neuropathy or grade 1 with pain within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, 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.
- Subject has hypersensitivity to bortezomib, boron or mannitol.
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Subject has been treated with more than two prior chemotherapy regimens
- Subject has been treated with a platinum-based regimen.
- Subject has received other investigational drugs with 14 days before enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Sites / Locations
- Unviersity of California Medical Center
Outcomes
Primary Outcome Measures
Determine the MTD of Velcade (bortezomib), Rituximab, Ifosfamide, Carboplatin, Etoposide (V-RICE) for patients with relapsed/primary refractory aggressive B-cell non-Hodgkin's lymphoma (NHL)
Secondary Outcome Measures
tolerability and safety, response rate, the amount of peripheral blood CD34+ progenitor cells collected and the rate of engraftment, assess the rate of autologous stem cell transplant
Full Information
NCT ID
NCT01300793
First Posted
September 24, 2009
Last Updated
September 24, 2012
Sponsor
University of California, San Francisco
Collaborators
Millennium Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01300793
Brief Title
Study of Standard-Dose Rituximab, Ifosfamide, Carboplatin and Etoposide
Acronym
V-RICE
Official Title
(RICE) Plus Bortezomib (Velcade) in a Dose-Escalating Fashion for Patients With Relapsed or Primary Refractory Aggressive B-Cell NHL
Study Type
Interventional
2. Study Status
Record Verification Date
September 2012
Overall Recruitment Status
Terminated
Why Stopped
closed for low accrual and no data is available.
Study Start Date
May 2007 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
April 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Millennium Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Primary objective of the study is to determine the maximum tolerated dose (MTD) of bortezomib (Velcade) in combination with rituximab, ifosfamide, carboplatin and etoposide for adult patients with relapsed or refractory aggressive B-cell lymphoma. The secondary objectives are to assess the tolerability and safety, the response rate, rate of autologous stem cell transplant and CD34+ progenitor cell collection and engraftment after treatment with this regimen.
Detailed Description
Once subjects are determined to be eligible and informed consent is obtained,patients will be enrolled into a starting dose cohort of 1.0mg/m2. Based upon a satisfactory safety profile, additional patients will be enrolled into the 1.3, 1.5 and 1.7mg/m2 cohorts. Each of these dosing cohorts will only be enrolled if satisfactory safety profiles in each of the lower dosing cohorts are obtained. As the process continues, multiple cohorts will be receiving various dosing regimens simultaneously. If a DLT occurs in ≥2 out of 6 patients at the initial dose level, then 3 more patients will be accrued at dose level -1 (0.7mg/m2).
Bortezomib will be given on days 1 (prior to rituximab) and 4, rituximab 375 mg/m2 on day 1, carboplatin AUC 5 and ifosfamide with mesna, each 5 gm/m2, on day 3 and etoposide 100 mg/ m2/day on days 2, 3 and 4 of a 21-day cycle. They will also receive filgrastim on days 6-13 or pegfilgrastim on day 6. Dose-limiting toxicities (DLT) include any grade 3 or 4 non-hematologic toxicities (except alopecia and grade 3 febrile neutropenia), grade 4 febrile neutropenia (life-threatening sepsis) and grade 4 neutropenia persisting past day 35 or grade 3 or 4 thrombocytopenia persisting past day 35.
If there is a DLT at a given bortezomib dose level, 3 more subjects will be enrolled at that dose; if there are 2 or more DLTs then the MTD will be defined as the previous dose level. If at that dose level, >50% of subjects required bortezomib dose reduction, the MTD will be defined as the next lower dose level. Subjects will continue to be accrued in order to treat a minimum of 10 patients at the MTD.
Those who are candidates for autologous stem cell transplant will have CT scan of the neck, chest, abdomen and pelvis after 2 cycles. Subjects with PD or SD will be taken off study. Those with CR, PR or response not meeting PR criteria will undergo a total of 3 cycles of bortezomib + RICE. After the 3rd cycle of bortezomib + RICE, whole body PET/CT scan and bone marrow biopsy will be obtained.
Subjects who achieve CR or PR will then proceed to stem cell mobilization and collection by a standard regimen, followed by autologous stem cell transplant with a preparative regimen to be determined by the investigator. Those with SD or PD will be taken off study. While the mobilization and ASCT procedures are not part of the phase I protocol, outcomes of ASCT will be followed, including CD34+ progenitor cell collection, clinical response to transplant and survival.
Subjects who are not candidates for autologous stem cell transplant will have CT scan of the neck, chest, abdomen and pelvis after the 2nd and 4th cycles. Those who are responding will continue for a maximum of 6 cycles.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma, B-cell Lymphoma
Keywords
V-RICE, Relapsed NHL, Primary Refractory NHL
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Velcade (bortezomib), rituximab, ifosfamide, carboplatin, etoposide
Other Intervention Name(s)
Velcade, VP-16, Carboplatin, Rituxan, ifosfamide
Intervention Description
Rituximab, 375 mg/m2, IV on day 1 Etoposide, 100 mg/m2, IV on days 2 to 4 Carboplatin, AUC 5 (using the Calvert Formula), IV on day 3 Ifosfamide, 5 g/m2 with Mesna 5 g/m2, CIV over 24 hours beginning D. 3 Bortezomib,1.0mg/m2 starting cohort. Based upon a satisfactory safety profile, additional pts. will be enrolled into the 1.3, 1.5 and 1.7mg/m2 cohorts given IVP over 3 sec. d. 1, 4, 8 & 11 q. 28 days.
Primary Outcome Measure Information:
Title
Determine the MTD of Velcade (bortezomib), Rituximab, Ifosfamide, Carboplatin, Etoposide (V-RICE) for patients with relapsed/primary refractory aggressive B-cell non-Hodgkin's lymphoma (NHL)
Time Frame
5 years
Secondary Outcome Measure Information:
Title
tolerability and safety, response rate, the amount of peripheral blood CD34+ progenitor cells collected and the rate of engraftment, assess the rate of autologous stem cell transplant
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aggressive B-cell non-Hodgkin lymphoma, CD-20 positive, in first relapse or refractory to first- or second-line chemotherapy (non-platinum)
Diffuse large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma (Grade III), Transformed Follicular Lymphoma
Prior Rituximab is allowed
Prior radiation is allowed
Prior autologous stem cell transplant is allowed
Age 18-70 years
ECOG performance status 0-2
HIV seronegative
No CNS involvement: CSF cytology is required for cases with bone marrow involvement, involvement of 2 or more extranodal sites, presentation in the testes or paranasal sinuses, or if any clinical suspicion of CNS involvement (e.g., cranial nerve deficits)
Measurable disease on CT scan by international working group response criteria • 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, intra-uterine 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:
Subject has a platelet count of less than 75,000.
Subject has an absolute neutrophil count of less than 1000
Subject has a calculated or measured creatinine clearance of <60 mL/minute within 14 days before enrollment.
Subject has grade 2 or greater peripheral neuropathy or grade 1 with pain within 14 days before enrollment.
Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, 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.
Subject has hypersensitivity to bortezomib, boron or mannitol.
Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
Subject has been treated with more than two prior chemotherapy regimens
Subject has been treated with a platinum-based regimen.
Subject has received other investigational drugs with 14 days before enrollment
Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lawrence Kaplan, M.D.
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
Unviersity of California Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Standard-Dose Rituximab, Ifosfamide, Carboplatin and Etoposide
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