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Rituximab, Cyclophosphamide, Bortezomib, and Prednisone in Patients With Stage III/IV FL or MZL

Primary Purpose

Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Rituximab
Bortezomib
Cyclophosphamide
Prednisone
Sponsored by
University of Miami
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring stage III grade 1 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma

Eligibility Criteria

17 Years - 120 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Histologically confirmed, untreated follicular lymphoma (FL) grade I, II or marginal zone lymphoma (MZL) Stage III or IV
  • Presence of measurable or evaluable disease
  • Age >17 years old

  • Patients must have normal organ and marrow function as defined below, within 14 days of enrollment:

    • Serum bilirubin < 2.0 mg/dL
    • serum creatinine < 2 mg/dL unless due to lymphoma
    • Absolute Neutrophil Count (ANC) >1000/mm3
    • Platelets >100,000/mm3 unless due to lymphoma
    • Aspartate Transaminase (AST), Alanine Aminotransferase (ALT) and Alkaline phosphatase < 3x the upper limit of normal
  • Eastern Cooperative Oncology Group (ECOG) performance status of 1, 2, 3
  • No prior therapy for the FL or MZL including chemotherapy, single agent rituximab and radiation therapy
  • 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

  • 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 Appendix 5), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  • 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 with 14 days before enrollment
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • History of HIV infection (testing not required)
  • Concurrent or previous malignancy whose prognosis is poor (< 90% probability of survival at 5 years) or those who are actively being treated for a second malignancy.

Sites / Locations

  • University of Miami Sylvester Comprehensive Cancer Center - Miami

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RCVELP

Arm Description

Rituximab, Cyclophosphamide, Bortezomib, Prednisone (RCVELP): Rituximab Induction: 375 mg/m2 IV infusion on Day 1 of every 21 days cycle for 8 cycles Maintenance: 375/m2 Days 1, 8, 15, 22 every 6 months for up to 4 cycles Cyclophosphamide: 750 mg/m2 intravenous piggyback (IVPB) on Day 1 of every 21 day cycle for 8 cycles Bortezomib: 1.6 mg/m2 IV push on Days 1 and 8 of every 21 days cycle for 8 cycles Prednisone: 100 mg PO daily on Days 1-5 of every 21 day cycle for 8 cycles

Outcomes

Primary Outcome Measures

Overall Response Rate, According to the International Workshop Criteria (IWC) for Non-Hodgkin's Lymphoma (NHL)
Rate of overall response (CR, CRu, PR) to protocol therapy according to International Workshop Criteria (IWC): Complete Response (CR) includes complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL; Complete Response Unconfirmed (CRu) includes above CR criteria but a residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the product of the perpendicular diameters (SPD), or indeterminate bone marrow; Partial Response (PR) includes >= 50% decrease in SPD of the six largest dominant nodes or nodal masses, no increase in size of other nodes, liver or spleen.

Secondary Outcome Measures

Progression-free Survival (PFS)
Progression free-survival will be assessed according to according to the International Workshop Criteria (IWC). Progression-free survival will be measured as the time from date of enrollment to relapse, progression or death due to follicular lymphoma (FL) or marginal zone lymphoma (MZL), whichever occurs first. Participants who do not experience relapse or progression, and those who die from causes other than cancer, will be censored at the date of last contact.
Overall Survival (OS)
Overall survival (OS) will be measured as the time from date of enrollment to death from any cause. For patients who remain alive, survival time will be censored at the date of last contact.
Rate of Toxicity in Study Participants
Safety and tolerance to protocol therapy as evidenced by the rate of toxicity (serious adverse events and study-related adverse events) in study participants

Full Information

First Posted
October 12, 2008
Last Updated
November 6, 2017
Sponsor
University of Miami
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1. Study Identification

Unique Protocol Identification Number
NCT00772668
Brief Title
Rituximab, Cyclophosphamide, Bortezomib, and Prednisone in Patients With Stage III/IV FL or MZL
Official Title
Pilot Study of RCVELP as First Line Therapy for Follicular Lymphoma (FL) and Marginal Zone Lymphoma (MZL)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Terminated
Why Stopped
Funding
Study Start Date
September 25, 2009 (Actual)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
February 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Miami

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving rituximab together with cyclophosphamide, bortezomib, and prednisone may kill more cancer cells. PURPOSE: This clinical trial is studying how well giving rituximab together with cyclophosphamide, bortezomib, and prednisone works as first-line therapy in treating patients with stage III or stage IV follicular lymphoma or marginal zone lymphoma.
Detailed Description
OUTLINE: Induction therapy: Patients receive rituximab IV and cyclophosphamide IV over 30 minutes on day 1, bortezomib IV on days 1 and 8, and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance therapy. Maintenance therapy: Patients receive rituximab IV on days 1, 8, 15, and 22. Treatment repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma
Keywords
stage III grade 1 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RCVELP
Arm Type
Experimental
Arm Description
Rituximab, Cyclophosphamide, Bortezomib, Prednisone (RCVELP): Rituximab Induction: 375 mg/m2 IV infusion on Day 1 of every 21 days cycle for 8 cycles Maintenance: 375/m2 Days 1, 8, 15, 22 every 6 months for up to 4 cycles Cyclophosphamide: 750 mg/m2 intravenous piggyback (IVPB) on Day 1 of every 21 day cycle for 8 cycles Bortezomib: 1.6 mg/m2 IV push on Days 1 and 8 of every 21 days cycle for 8 cycles Prednisone: 100 mg PO daily on Days 1-5 of every 21 day cycle for 8 cycles
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
Administered intravenously during induction and maintenance therapy per protocol.
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
Administered intravenously per protocol.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
Administered intravenously per protocol.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
Deltasone
Intervention Description
Administered orally (PO) per protocol.
Primary Outcome Measure Information:
Title
Overall Response Rate, According to the International Workshop Criteria (IWC) for Non-Hodgkin's Lymphoma (NHL)
Description
Rate of overall response (CR, CRu, PR) to protocol therapy according to International Workshop Criteria (IWC): Complete Response (CR) includes complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities definitely assignable to NHL; Complete Response Unconfirmed (CRu) includes above CR criteria but a residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the product of the perpendicular diameters (SPD), or indeterminate bone marrow; Partial Response (PR) includes >= 50% decrease in SPD of the six largest dominant nodes or nodal masses, no increase in size of other nodes, liver or spleen.
Time Frame
Post cycles 2,4,6,8 and then every 3 months, about 2 years
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
Progression free-survival will be assessed according to according to the International Workshop Criteria (IWC). Progression-free survival will be measured as the time from date of enrollment to relapse, progression or death due to follicular lymphoma (FL) or marginal zone lymphoma (MZL), whichever occurs first. Participants who do not experience relapse or progression, and those who die from causes other than cancer, will be censored at the date of last contact.
Time Frame
Up to 5 years
Title
Overall Survival (OS)
Description
Overall survival (OS) will be measured as the time from date of enrollment to death from any cause. For patients who remain alive, survival time will be censored at the date of last contact.
Time Frame
Up to 5 years
Title
Rate of Toxicity in Study Participants
Description
Safety and tolerance to protocol therapy as evidenced by the rate of toxicity (serious adverse events and study-related adverse events) in study participants
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
17 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion 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. Histologically confirmed, untreated follicular lymphoma (FL) grade I, II or marginal zone lymphoma (MZL) Stage III or IV Presence of measurable or evaluable disease Age >17 years old Patients must have normal organ and marrow function as defined below, within 14 days of enrollment: Serum bilirubin < 2.0 mg/dL serum creatinine < 2 mg/dL unless due to lymphoma Absolute Neutrophil Count (ANC) >1000/mm3 Platelets >100,000/mm3 unless due to lymphoma Aspartate Transaminase (AST), Alanine Aminotransferase (ALT) and Alkaline phosphatase < 3x the upper limit of normal Eastern Cooperative Oncology Group (ECOG) performance status of 1, 2, 3 No prior therapy for the FL or MZL including chemotherapy, single agent rituximab and radiation therapy 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 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 Appendix 5), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. 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 with 14 days before enrollment Serious medical or psychiatric illness likely to interfere with participation in this clinical study. History of HIV infection (testing not required) Concurrent or previous malignancy whose prognosis is poor (< 90% probability of survival at 5 years) or those who are actively being treated for a second malignancy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Denise Pereira, MD
Organizational Affiliation
University of Miami Sylvester Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Miami Sylvester Comprehensive Cancer Center - Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Rituximab, Cyclophosphamide, Bortezomib, and Prednisone in Patients With Stage III/IV FL or MZL

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