Clinical trial NCT00772668: 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
Overall status: TERMINATED
Phase: NA
Conditions: 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
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2008-10-15
Enrollment: 3
Sex: ALL
Minimum age (years): 17
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall Response Rate, According to the International Workshop Criteria (IWC) for Non-Hodgkin's Lymphoma (NHL)
timeFrame: Post cycles 2,4,6,8 and then every 3 months, about 2 years
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to 5 years
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Rate of Toxicity in Study Participants
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
Study officials:
affiliation: University of Miami Sylvester Comprehensive Cancer Center
name: Denise Pereira, MD
role: PRINCIPAL_INVESTIGATOR
References: