Overview

This trial is active, not recruiting.

Conditions contiguous stage ii mantle cell lymphoma, noncontiguous stage ii mantle cell lymphoma, stage i mantle cell lymphoma, stage iii mantle cell lymphoma, stage iv mantle cell lymphoma
Treatments bortezomib, rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, dexamethasone, filgrastim, pegfilgrastim, laboratory biomarker analysis
Phase phase 2
Targets CD20, proteasome
Sponsor National Cancer Institute (NCI)
Start date May 2007
End date July 2012
Trial size 72 participants
Trial identifier NCT00433537, E1405, ECOG-E1405, NCI-2012-02966, U10CA021115

Summary

This phase II trial is studying how well giving rituximab together with combination chemotherapy and bortezomib works in treating patients with untreated mantle cell lymphoma. 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, doxorubicin, vincristine, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving rituximab together with combination chemotherapy and bortezomib may kill more cancer cells.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Induction therapy (VcR-CVAD): Patients receive VcR-CVAD comprising bortezomib IV over 3-5 seconds on days 1 and 4; rituximab IV over 3-4 hours on day 1; doxorubicin hydrochloride IV over 48 hours on days 1 and 2; cyclophosphamide IV over 3 hours every 12 hours on days 1-3; vincristine IV over 3-5 seconds on day 3; and dexamethasone IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) SC or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Maintenance therapy: Beginning 4-8 weeks after completion of induction therapy, patients receive rituximab IV over 3-4 hours once weekly for 4 weeks. Treatment repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of induction therapy, patients who a
bortezomib LDP 341
Given IV
rituximab IDEC-C2B8
Given IV
cyclophosphamide CPM
Given IV
doxorubicin hydrochloride ADM
Given IV
vincristine sulfate leurocristine sulfate
Given IV
dexamethasone Aeroseb-Dex
Given IV
filgrastim G-CSF
Given SC
pegfilgrastim Filgrastim SD-01
Given SC
laboratory biomarker analysis
Correlative studies

Primary Outcomes

Measure
Rate of CR defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy
time frame: Up to 10 years

Secondary Outcomes

Measure
Overall response rate
time frame: Up to 10 years
Progression-free survival
time frame: From entry onto study until lymphoma progression or death form any cause, assessed up to 10 years
Overall survival
time frame: The date of study entry to the date of death, assessed up to 10 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Patients must have a histologically confirmed diagnosis of mantle cell lymphoma by demonstrating appropriate morphology plus at least one of the following on the biopsy specimen: nuclear cyclin D1+ by imunohistochemistry; t(11;14) by FISH, PCR, or conventional karyotyping - No prior chemotherapy, immunotherapy or radiotherapy for mantle cell lymphoma; a brief course of steroids (< 14 days) for symptom relief or steroids for other indications are allowed - Patients must have measurable disease; CT scans at baseline are required to define the extent of measurable disease; the scans must be obtained within 6 weeks prior to registration; combined CT/PET scans may be used for the baseline and subsequent evaluations if accurate tumor measurements can be obtained from the CT component - ECOG performance status 0-2 - ANC > 1500 mm^3 (unless low count due to marrow involvement or splenomegaly) - Platelets > 100,000 mm^3 (unless low counts due to marrow involvement or splenomegaly) - Creatinine < 2 mg/dL - Bilirubin < 2 mg/dL (may be up to 3.0 mg/dL if due to Gilbert's disease or due to liver involvement by lymphoma) - Patients over the age of 45 must have a LVEF of greater than 45% documented within 90 days prior to registration - No known HIV disease; an HIV test is not required for entry on study but is required if the patient is perceived to be at risk; patients with a history of intravenous drug use or any other behavior with an increased risk for HIV infection should be tested for exposure to the HIV virus; patients with known HIV are excluded since the immunocompromised state of patients with HIV infection or the concomitant use of HAART therapy may result in more extensive dose modifications than intended for the intensive therapeutic regimen used in this study - Patients must be tested for Hepatitis B surface antigen within 4 weeks prior to registration NOTE: HBs Ag positive patients are not excluded but will have more stringent monitoring of LFTs - Women must not be pregnant or breast-feeding due to the detrimental effects chemotherapy may have on the developing fetus or infant; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy - Women of childbearing potential and sexually active males must use an accepted and effective method of contraception - Patient must not have grade 2 or higher baseline peripheral neuropathy - Patient must not have known hypersensitivity to boron or mannitol - Patient may not have a history of prior malignancy unless at least one of the following conditions are met: - Malignancy was in-situ - Malignancy was treated surgically or with local XRT with curative intent and the patient has been disease free for > 3 years - Any adjuvant hormonal therapy must have been discontinued > 3 months prior to registration - Patients must not have known CNS involvement

Additional Information

Official title A Phase II Study of VcR-CVAD With Rituximab Maintenance for Untreated Mantle Cell Lymphoma
Principal investigator Brad Kahl
Description PRIMARY OBJECTIVES: I. To evaluate the CR rate in patients with mantle cell lymphoma, who are treated with VcR-CVAD. SECONDARY OBJECTIVES: I. To evaluate the overall response rate to VcR-CVAD. II. To evaluate the PFS and OS of patients receiving maintenance rituximab after VcRCVAD induction. III. To evaluate the PFS and OS of patients who receive autologous stem cell transplantation after VcR-CVAD induction. IV. To evaluate the toxicity of VcR-CVAD. TERTIARY OBJECTIVES: I. Evaluation of antigen expression patterns to determine or confirm possible unique expressions of MCL. II. To evaluate the percentage of circulating MCL cells. OUTLINE: This is a multicenter study. Induction therapy (VcR-CVAD): Patients receive VcR-CVAD comprising bortezomib IV over 3-5 seconds on days 1 and 4; rituximab IV over 3-4 hours on day 1; doxorubicin hydrochloride IV over 48 hours on days 1 and 2; cyclophosphamide IV over 3 hours every 12 hours on days 1-3; vincristine IV over 3-5 seconds on day 3; and dexamethasone IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) subcutaneously (SC) or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Maintenance therapy: Beginning 4-8 weeks after completion of induction therapy, patients receive rituximab IV over 3-4 hours once weekly for 4 weeks. Treatment repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of induction therapy, patients who are eligible may have the option to receive consolidation therapy for autologous stem cell transplantation (off-study). These patients undergo stem cell harvest during courses 4, 5, or 6 of induction therapy. After completion of study treatment, patients are followed periodically for up to 10 years.
Trial information was received from ClinicalTrials.gov and was last updated in July 2013.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).