Bortezomib After Combination Chemotherapy, Rituximab, and an Autologous Stem Cell Transplant in Treating Patients With Mantle Cell Lymphoma

NCT00310037 | Completed Phase 2 Results DMC

• 2 other identifiers: CALGB-50403CDR0000466167
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 48

Brief Summary

This randomized phase II trial studies how well bortezomib works when given after combination chemotherapy, rituximab, and an autologous stem cell transplant in treating patients with mantle cell lymphoma. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with an autologous stem cell transplant may allow more chemotherapy to be given so that more cancer cells are killed. 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. Giving bortezomib after combination chemotherapy, monoclonal antibody therapy, and an autologous stem cell transplant may kill any remaining cancer cells or keep the cancer from coming back.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival Rate at 18 Months

  Progression free survival (PFS) rate at 18 months was defined as the proportion of patients that were alive and progression-free 18 months after registration into the study. The Kaplan-Meier method of 18 month progression-free survival was calculated..

  At 18 months

Secondary Outcomes (3)

• Overall Survival

  Up to 10 years

• Number of Participants With Complete Response Intensive Chemo-immunotherapy Plus Maintenance or Consolidation Bortezomib

  Up to 10 years

• Number of Participants With Grade 3, 4 or 5 Adverse Event at Least Possibly Related to Treatment.

  Duration of treatment (up to approximately 2 years)

Study Arms (2)

Arm A maintenance therapy

EXPERIMENTAL

Patients receive bortezomib 1.6 mg/m\^2 IV on days 1, 8, 15, and 22 once daily for 4 weeks. There will be a 4 week rest period. One cycle is a total of 8 weeks. A total of 10 cycles of bortezomib will be given in the absence of disease progression or unacceptable toxicity.

Drug: bortezomib

Arm B consolidation therapy

EXPERIMENTAL

Patients receive bortezomib 1.3 mg/m\^2 IV on days 1, 4, 8, and 11 once daily for 3 weeks. One cycle is a total of 3 weeks. A total of 4 cycles of bortezomib will be given in the absence of disease progression or unacceptable toxicity.

Drug: bortezomib

Interventions

bortezomib DRUG

Given IV

Arm A maintenance therapy; Arm B consolidation therapy

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

1. Documentation of Disease A. Histologic Documentation: * Histologically documented mantle cell lymphoma with co-expression of CD20 (or CD19) and CD5 and lack of CD23 expression by immunophenotyping AND at least one of the following confirmatory tests: * positive immunostaining for cyclin D1; OR * the presence of t(11;14) on cytogenetic analysis; OR * molecular evidence of bcl-1/IgH rearrangement. * Cases that are CD5-negative and/or CD23-positive will be eligible provided that the histopathology is consistent with mantle cell lymphoma AND positive for cyclin D1, t(11;14), or bcl-1/IgH rearrangement.A tissue block should be submitted to the CALGB Pathology Coordinating Office for central pathology review. * A diagnosis based on peripheral blood or bone marrow is allowed. If the diagnosis is based only on blood, in addition to the immunophenotype and molecular confirmation above, a peripheral blood smear must be available for central pathology review. If the diagnosis is based on a bone marrow biopsy, the tissue block should be submitted. * Note: Failure to submit pathology materials within 60 days of patient registration will be considered a major protocol violation. B. Extent of Disease: * Stage I-IV. Patients with nodular histology mantle cell lymphoma must have Ann Arbor stage III or IV disease to be eligible. Patients with mantle zone histology will not be eligible because of their relatively favorable prognosis. Patients with other mantle cell histologies are eligible regardless of stage. * No active CNS disease defined as symptomatic meningeal lymphoma or known CNS parenchymal lymphoma. A lumbar puncture demonstrating mantle cell lymphoma at the time of registration to this study is not an exclusion for study enrollment. 2. Prior Treatment: A. Patients must be previously untreated or have received no more than one prior cycle of chemotherapy and/or rituximab treatment. B. No prior radiation therapy for mantle cell lymphoma. C. ≥ 2 weeks since major surgery. D. ≥ 3 weeks since prior chemotherapy. 3. Age Eligibility: Age ≥ 18 years and \< 70 years 4. Murine Products Hypersensitivity Eligibility: No known hypersensitivity to murine products. 5. Use of Systemic Corticosteroids Eligibility: No medical condition requiring chronic use of systemic corticosteroids. 6. Eligibility Criteria on HIV Infection: No HIV infection. Patients with a history of intravenous drug abuse or any behavior associated with an increased risk of HIV infection should be tested for exposure to the HIV virus. Patients who test positive or who are known to be infected are not eligible due to an increased risk of infection with this regimen. An HIV test is not required for entry on this protocol, but is required if the patient is perceived to be at risk. 7. Non-pregnant and non-nursing: Non-pregnant and non-nursing. Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control. 8. HepBSAg or HepC Ab Eligibility: Patients who test positive for HepBSAg or HepC Ab are eligible provided all of the following criteria are met: A. bilirubin ≤ 2 x upper limit of normal; AND B. AST ≤ 3 x upper limit of normal; AND C. liver biopsy demonstrates ≤ grade 2 fibrosis and no cirrhosis. Hepatitis B surface Ag(+) patients will be treated with lamivudine (3TC) throughout protocol therapy and for 6-12 months thereafter. 9. Secondary Malignancy Eligibility: Patients with a "currently active" second malignancy, other than non-melanoma skin cancers are not eligible. This includes Waldenstrom's Macroglobulinemia, since such patents have experienced transient increases in IgM following initiation of rituximab, with the potential for hyperviscosity syndrome requiring plasmapheresis. Patients are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy, and are considered by their physician to be at less than 30% risk of relapse. 10. Initial Required Laboratory Values: * LVEF by MUGA or ECHO ≥ 45% * Creatinine ≤ 2.0 mg/dL * Total Bilirubin ≤ 2.0 mg/dL (Unless attributable to Gilbert's Disease) * u-HCG or serum HCG Negative (If patient of childbearing potential).

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (48)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Illinois CancerCare - Bloomington

Bloomington, Illinois, 61701, United States

Location

St. Joseph Medical Center

Bloomington, Illinois, 61701, United States

Location

Graham Hospital

Canton, Illinois, 61520, United States

Location

Illinois CancerCare - Canton

Canton, Illinois, 61520, United States

Location

Illinois CancerCare - Carthage

Carthage, Illinois, 62321, United States

Location

Memorial Hospital

Carthage, Illinois, 62321, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

Eureka Community Hospital

Eureka, Illinois, 61530, United States

Location

Illinois CancerCare - Eureka

Eureka, Illinois, 61530, United States

Location

Galesburg Clinic, PC

Galesburg, Illinois, 61401, United States

Location

Illinois CancerCare - Galesburg

Galesburg, Illinois, 61401, United States

Location

Illinois CancerCare - Havana

Havana, Illinois, 62644, United States

Location

Mason District Hospital

Havana, Illinois, 62644, United States

Location

Illinois CancerCare - Kewanee Clinic

Kewanee, Illinois, 61443, United States

Location

Illinois CancerCare - Macomb

Macomb, Illinois, 61455, United States

Location

McDonough District Hospital

Macomb, Illinois, 61455, United States

Location

Illinois CancerCare - Monmouth

Monmouth, Illinois, 61462, United States

Location

OSF Holy Family Medical Center

Monmouth, Illinois, 61462, United States

Location

BroMenn Regional Medical Center

Normal, Illinois, 61761, United States

Location

Community Cancer Center

Normal, Illinois, 61761, United States

Location

Illinois CancerCare - Community Cancer Center

Normal, Illinois, 61761, United States

Location

Community Hospital of Ottawa

Ottawa, Illinois, 61350, United States

Location

Oncology Hematology Associates of Central Illinois, PC - Ottawa

Ottawa, Illinois, 61350, United States

Location

Illinois CancerCare - Pekin

Pekin, Illinois, 61603, United States

Location

Proctor Hospital

Peoria, Illinois, 61614, United States

Location

CCOP - Illinois Oncology Research Association

Peoria, Illinois, 61615, United States

Location

Oncology Hematology Associates of Central Illinois, PC - Peoria

Peoria, Illinois, 61615, United States

Location

Methodist Medical Center of Illinois

Peoria, Illinois, 61636, United States

Location

OSF St. Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Illinois CancerCare - Peru

Peru, Illinois, 61354, United States

Location

Illinois Valley Community Hospital

Peru, Illinois, 61354, United States

Location

Illinois CancerCare - Princeton

Princeton, Illinois, 61356, United States

Location

Perry Memorial Hospital

Princeton, Illinois, 61356, United States

Location

Illinois CancerCare - Spring Valley

Spring Valley, Illinois, 61362, United States

Location

Dana-Farber/Brigham and Women's Cancer Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756-0002, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Monter Cancer Center of the North Shore-LIJ Health System

Lake Success, New York, 11042, United States

Location

CCOP - North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Don Monti Comprehensive Cancer Center at North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210-1240, United States

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Lawrence D. Kaplan, MD
• Organization: University of California, San Francisco

lkaplan@medicine.ucsf.edu

Study Officials

• Lawrence D. Kaplan, MD

  University of California, San Francisco

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2006
• First Posted: April 3, 2006
• Study Start: June 1, 2006
• Primary Completion: December 1, 2013
• Study Completion: June 1, 2022
• Last Updated: October 28, 2025
• Results First Posted: July 31, 2018

Record last verified: 2025-10

Locations

US (48)