Combination Chemotherapy and Rituximab in Treating Patients With Untreated Mantle Cell Lymphoma
A Phase II Study of VcR-CVAD With Rituximab Maintenance for Untreated Mantle Cell Lymphoma
3 other identifiers
interventional
77
1 country
1
Brief 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. Treatment consists of six agents: bortezomib (Vc), rituximab (R), cyclophosphamide (C), vincristine (V), doxorubicin (A), and dexamethasone (D) (VcR-CVAD).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started May 2007
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 8, 2007
CompletedFirst Posted
Study publicly available on registry
February 12, 2007
CompletedStudy Start
First participant enrolled
May 1, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2013
CompletedResults Posted
Study results publicly available
October 30, 2014
CompletedOctober 30, 2014
January 1, 2014
6.1 years
February 8, 2007
October 24, 2014
October 24, 2014
Conditions
Outcome Measures
Primary Outcomes (1)
Complete Response (CR) Rate
Number of eligible, treated participants who achieve complete response. Response criteria are based upon the criteria from the Revised Response Criteria for Malignant Lymphoma (Cheson et al., 2007). Complete response is defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy.
Assessed after VcR-CVAD cycles 2, 4, and 6.
Secondary Outcomes (2)
2-year Progression-free Survival (PFS)
Assessed every 6 months for 5 years, and then yearly thereafter.
3-year Overall Survival (OS)
Assessed every 6 months for 5 years, and then yearly thereafter.
Study Arms (2)
VcR-CVAD induction followed by maintenance rituximab
EXPERIMENTALVcR-CVAD induction: 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 rituximab: 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.
VcR-CVAD induction followed by ASCT
EXPERIMENTALVcR-CVAD induction: 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. ASCT: 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.
Interventions
Given IV
Given IV
Given IV
Given IV
Given IV
Given IV
Given SC
Given SC
Eligibility Criteria
You may qualify if:
- 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 immunohistochemistry; t(11;14) by fluorescence in situ hybridization (FISH), polymerase chain reaction (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
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count (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 left ventricular ejection fraction (LVEF) of greater than 45% documented within 90 days prior to registration
- Patients must be tested for Hepatitis B surface antigen (HBs Ag) within 4 weeks prior to registration NOTE: HBs Ag positive patients are not excluded but will have more stringent monitoring of liver function tests
You may not qualify if:
- 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 highly active antiretroviral therapy (HAART) may result in more extensive dose modifications than intended for the intensive therapeutic regimen used in this study
- Pregnant or breast-feeding; 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
- Grade 2 or higher baseline peripheral neuropathy
- Known hypersensitivity to boron or mannitol
- 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 radiation therapy 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
- Known central nervous system (CNS) involvement
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Eastern Cooperative Oncology Group
Boston, Massachusetts, 02215, United States
Related Publications (1)
Chang JE, Li H, Smith MR, Gascoyne RD, Paietta EM, Yang DT, Advani RH, Horning SJ, Kahl BS. Phase 2 study of VcR-CVAD with maintenance rituximab for untreated mantle cell lymphoma: an Eastern Cooperative Oncology Group study (E1405). Blood. 2014 Mar 13;123(11):1665-73. doi: 10.1182/blood-2013-08-523845. Epub 2014 Jan 23.
PMID: 24458437DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Statistician
- Organization
- ECOG Statistical Office
Study Officials
- STUDY CHAIR
Brad Kahl
Eastern Cooperative Oncology Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 8, 2007
First Posted
February 12, 2007
Study Start
May 1, 2007
Primary Completion
June 1, 2013
Study Completion
June 1, 2013
Last Updated
October 30, 2014
Results First Posted
October 30, 2014
Record last verified: 2014-01