Non-Hodgkin's LymphomaPhase 1V-RICENCT01300793
Study of Standard-Dose Rituximab, Ifosfamide, Carboplatin and Etoposide
A Phase 1 study testing Velcade (bortezomib), rituximab, ifosfamide, carboplatin, etoposide in people with Non-Hodgkin's Lymphoma and B-cell Lymphoma, run by University of California, San Francisco at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin's Lymphoma, B-cell Lymphoma
- What is being tested?
- Velcade (bortezomib), rituximab, ifosfamide, carboplatin, etoposide
- Type of treatment
- Injection or infusion
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- May 2007to Apr 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Unviersity of California Medical Center
San Francisco, California, 94143
About this study
Official title: (RICE) Plus Bortezomib (Velcade) in a Dose-Escalating Fashion for Patients With Relapsed or Primary Refractory Aggressive B-Cell NHL
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.
Read the 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.
- Conditions
- Non-Hodgkin's Lymphoma, B-cell Lymphoma
- Being tested
- Velcade (bortezomib), rituximab, ifosfamide, carboplatin, etoposide
- Keywords
- V-RICE, Relapsed NHL, Primary Refractory NHL
- Medical subject headings
- Lymphoma, Non-Hodgkin, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Velcade (bortezomib), rituximab, ifosfamide, carboplatin, etoposideDrug
Also called Velcade, VP-16, Carboplatin, Rituxan, ifosfamide
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 5 years
Secondary outcomes (1)
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
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2011 (estimated)
- Study startMay 2007
- Primary completionJul 2011
- Study completionApr 2012
Why it stopped: closed for low accrual and no data is available.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Lawrence Kaplan, M.D., Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01300793
- Sponsor's protocol ID
- 06253
- Acronym
- V-RICE
- Status last verified
- Sep 2012
- First submitted
- 24 Sep 2009
- Last updated
- 26 Sep 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- (RICE) Plus Bortezomib (Velcade) in a Dose-Escalating Fashion for Patients With Relapsed or Primary Refractory Aggressive B-Cell NHL
- ClinicalTrials.gov ID
- NCT01300793
- Acronym / sponsor ID
- V-RICE / 06253
- Conditions
- Non-Hodgkin's Lymphoma, B-cell Lymphoma
- Keywords
- V-RICE, Relapsed NHL, Primary Refractory NHL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: closed for low accrual and no data is available.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- May 2007
- Primary completion
- Jul 2011 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 23 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Aggressive B-cell non-Hodgkin lymphoma, CD-20 positive, in first relapse or refractory to first- or second-line chemotherapy (non-platinum)
- 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)
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Velcade (bortezomib), rituximab, ifosfamide, carboplatin, etoposideAlso: Velcade, VP-16, Carboplatin, Rituxan, ifosfamideRituximab, 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. | Drug | – |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study was stopped early (reason given: closed for low accrual and no data is available.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lawrence Kaplan, M.D. principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Velcade (bortezomib), rituximab, ifosfamide, carboplatin, etoposide in people with Non-Hodgkin's Lymphoma and B-cell Lymphoma, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: closed for low accrual and no data is available.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2012.