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Mantle Cell LymphomaPhase 2NCT00310037

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

A Phase 2 study testing bortezomib in people with Mantle Cell Lymphoma, run by Alliance for Clinical Trials in Oncology at 48 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 69 years
Conditions the study is for
Mantle Cell Lymphoma
What is being tested?
bortezomib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
151 participants
Where
48 sitesUnited States
Study dates
Jun 2006to Jun 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 69 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult
  1. Documentation of Disease
  2. 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.
  1. 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.
  1. Prior Treatment:
  2. Patients must be previously untreated or have received no more than one prior cycle of chemotherapy and/or rituximab treatment.
  3. No prior radiation therapy for mantle cell lymphoma.
  4. ≥ 2 weeks since major surgery.
  5. ≥ 3 weeks since prior chemotherapy.
  6. Age Eligibility: Age ≥ 18 years and < 70 years
  7. Murine Products Hypersensitivity Eligibility: No known hypersensitivity to murine products.
  8. Use of Systemic Corticosteroids Eligibility: No medical condition requiring chronic use of systemic corticosteroids.
  9. 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.
  10. 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.
  11. HepBSAg or HepC Ab Eligibility: Patients who test positive for HepBSAg or HepC Ab are eligible provided all of the following criteria are met:
  12. bilirubin ≤ 2 x upper limit of normal; AND
  13. AST ≤ 3 x upper limit of normal; AND
  14. 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.
  15. 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.
  16. 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).

Trial locations and contacts

48 sites in 1 country.

48 sites in 1 country

United States48 sites
  • Illinois CancerCare - Bloomington

    Bloomington, Illinois, 61701

  • St. Joseph Medical Center

    Bloomington, Illinois, 61701

  • Dana-Farber/Brigham and Women's Cancer Center

    Boston, Massachusetts, 02115

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

    Boston, Massachusetts, 02115

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263-0001

  • Graham Hospital

    Canton, Illinois, 61520

  • Illinois CancerCare - Canton

    Canton, Illinois, 61520

  • Illinois CancerCare - Carthage

    Carthage, Illinois, 62321

  • Memorial Hospital

    Carthage, Illinois, 62321

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

    Chapel Hill, North Carolina, 27599-7295

  • University of Chicago Cancer Research Center

    Chicago, Illinois, 60637-1470

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

    Columbus, Ohio, 43210-1240

  • Eureka Community Hospital

    Eureka, Illinois, 61530

  • Illinois CancerCare - Eureka

    Eureka, Illinois, 61530

  • Galesburg Clinic, PC

    Galesburg, Illinois, 61401

  • Illinois CancerCare - Galesburg

    Galesburg, Illinois, 61401

  • Illinois CancerCare - Havana

    Havana, Illinois, 62644

  • Mason District Hospital

    Havana, Illinois, 62644

  • Illinois CancerCare - Kewanee Clinic

    Kewanee, Illinois, 61443

  • Monter Cancer Center of the North Shore-LIJ Health System

    Lake Success, New York, 11042

  • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756-0002

  • Illinois CancerCare - Macomb

    Macomb, Illinois, 61455

  • McDonough District Hospital

    Macomb, Illinois, 61455

  • CCOP - North Shore University Hospital

    Manhasset, New York, 11030

  • Don Monti Comprehensive Cancer Center at North Shore University Hospital

    Manhasset, New York, 11030

  • Illinois CancerCare - Monmouth

    Monmouth, Illinois, 61462

  • OSF Holy Family Medical Center

    Monmouth, Illinois, 61462

  • Long Island Jewish Medical Center

    New Hyde Park, New York, 11040

  • BroMenn Regional Medical Center

    Normal, Illinois, 61761

  • Community Cancer Center

    Normal, Illinois, 61761

  • Illinois CancerCare - Community Cancer Center

    Normal, Illinois, 61761

  • Community Hospital of Ottawa

    Ottawa, Illinois, 61350

  • Oncology Hematology Associates of Central Illinois, PC - Ottawa

    Ottawa, Illinois, 61350

  • Illinois CancerCare - Pekin

    Pekin, Illinois, 61603

  • Proctor Hospital

    Peoria, Illinois, 61614

  • CCOP - Illinois Oncology Research Association

    Peoria, Illinois, 61615

  • Oncology Hematology Associates of Central Illinois, PC - Peoria

    Peoria, Illinois, 61615

  • Methodist Medical Center of Illinois

    Peoria, Illinois, 61636

  • OSF St. Francis Medical Center

    Peoria, Illinois, 61637

  • Illinois CancerCare - Peru

    Peru, Illinois, 61354

  • Illinois Valley Community Hospital

    Peru, Illinois, 61354

  • Illinois CancerCare - Princeton

    Princeton, Illinois, 61356

  • Perry Memorial Hospital

    Princeton, Illinois, 61356

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

  • Illinois CancerCare - Spring Valley

    Spring Valley, Illinois, 61362

  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    St Louis, Missouri, 63110

  • SUNY Upstate Medical University Hospital

    Syracuse, New York, 13210

  • Wake Forest University Comprehensive Cancer Center

    Winston-Salem, North Carolina, 27157-1096

Other trials in United States

About this study

Official title: A Randomized Phase II Trial of Maintenance vs Consolidation Bortezomib Therapy Following Aggressive Chemo-Immunotherapy and Autologous Stem Cell Transplant for Previously Untreated Mantle Cell Lymphoma

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.

Read the detailed description

Objectives

Primary Objective:

To determine the 18-month progression-free survival (PFS) in patients with previously untreated mantle cell lymphoma who are treated with aggressive chemo-immunotherapy and autologous stem cell transplant followed by randomization to either maintenance or consolidation bortezomib therapy

Secondary Objectives:

  • To determine the toxicity profiles of maintenance and consolidation bortezomib by evaluating the number of patients able to complete all maintenance or consolidation therapy
  • To determine the complete response rate to intensive chemo-immunotherapy plus maintenance or consolidation bortezomib
  • To determine time to progression and overall survival using these two treatment regimens

Correlative/Other Pre-Specified Objectives:

  • To determine the importance of p53 mutation or deletion on patient outcome with respect to CR rate, PFS, and OS
  • To determine the importance of Ki67, cyclin D1, phosphohistone 3, p27, p21, p16, and PARP p85 expression in pre-treatment tumor biopsies with respect to CR rate, PFS, and OS
  • To determine the relationship between proliferation signature and clinical outcome using quantitative real-time RT-PCR
  • To evaluate the importance of quantitative cyclin D1 expression and expression of cyclin D1 isoforms in predicting clinical outcome using quantitative real-time RT-PCR
  • To evaluate the prognostic significance of microRNAs in mantle cell lymphoma using microRNA arras
  • To explore the correlation of selected microRNA polymorphisms with gene target expression with clinical outcomes such as response, PFS, and OS
  • To determine changes in gene expression profile from diagnosis to relapse samples to identify genes differentially silenced or over-expressed with disease recurrence
  • To determine the importance of early PCR negativity (following Treatment 2) using bcl-1/IgH junction and/or IgH chain gene rearrangement with respect to maintained PFS and the success of maintenance or consolidation therapy to converting patients to PCR negative status

OUTLINE OF INTERVENTIONS:

CHEMOIMMUNOTHERAPY: Patients receive chemoimmunotherapy comprising rituximab* intravenously (IV) over 4-6 hours on day 1, methotrexate (MTX) IV over 4 hours on day 2, cyclophosphamide IV over 2 hours, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 3, and prednisone orally (PO) on days 3-7. Beginning 24 hours after completion of MTX, patients receive leucovorin calcium IV every 6 hours until blood levels of MTX are in a safe range. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily (QD) beginning on day 3 and continuing until blood counts recover. Beginning no sooner than day 22, but no later that day 29 of the first course, patients receive a second course of chemoimmunotherapy as above. Patients with > 15% persistent bone marrow involvement may receive a third course of chemoimmunotherapy. Patients are restaged and those with progressive disease are removed from therapy.

NOTE: *During the first course of chemoimmunotherapy, patients receive rituximab only if the number of circulating mantle cells is =< 10,000/mm^3, otherwise, rituximab is omitted during the first course of chemoimmunotherapy.

HIGH-DOSE CONSOLIDATION CHEMOIMMUNOTHERAPY AND PERIPHERAL BLOOD STEM CELL (PBSC) COLLECTION: Approximately 4 weeks after completion of chemoimmunotherapy, patients receive high-dose consolidation chemoimmunotherapy comprising cytarabine IV over 2 hours and etoposide phosphate IV continuously on days 1-4, and rituximab IV over 4-6 hours on days 5 and 12 OR 6 and 13. Beginning on day 14 and continuing until completion of PBSC collection, patients receive G-CSF SC QD. Once blood counts recover, patients undergo 1-3 leukapheresis procedures for collection of PBSCs on days 22-25.

HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS PBSC TRANSPLANTATION (PBSCT): Beginning 4-6 weeks after completion of leukapheresis, patients receive carmustine IV over 2 hours on day -6, etoposide phosphate IV over 4 hours on day -4, and cyclophosphamide IV over 2 hours on day -2. Patients undergo autologous PBSCT on day 0. Patients also receive G-CSF SC QD beginning on day 4 and continuing until blood counts recover.

POST-TRANSPLANTATION IMMUNOTHERAPY: Approximately 5 weeks after autologous PBSCT, patients receive rituximab IV over 4-6 hours once weekly for 2 weeks. Approximately 4 weeks after completion of post-transplantation immunotherapy, patients proceed to maintenance therapy or consolidation therapy with bortezomib as described in the Arms section.

After completion of study treatment, patients are followed every 2 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

Being tested
bortezomib
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00310037
Study groupRoleWhat they receive
Arm A maintenance therapyExperimentalPatients 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.
Receives: Drug: bortezomib
Arm B consolidation therapyExperimentalPatients 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.
Receives: Drug: bortezomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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..

    Measured: At 18 months

Secondary outcomes (3)
  1. Overall Survival

    Overall Survival (OS) was measured from the date of study entry to date of death due to any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.

    Measured: Up to 10 years

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

    Complete response is:

    • Complete disappearance of all detectable clinical and radiographic evidence of target lesions and disappearance of all disease-related symptoms if present prior to therapy and normalization of biochemical abnormalities definitely assignable to NHL
    • All lymph nodes and nodal masses must have regressed to normal size (<= 1.5 cm in the greatest transverse diameter (GTD) for nodes > 1.5 cm prior to therapy) or <= 1 cm for nodes that were 1.1-1.5 cm in the GTD prior to therapy or by more than 75% in the sum of the products of the GTD
    • The spleen, if enlarged before therapy, must have regressed in size and must not be palpable on physical examination. Any macroscopic nodules in any organs detectable on imaging studies should no longer be present. Other organs enlarged prior to therapy due to involvement of lymphoma must have decreased in size
    • If bone marrow was involved by lymphoma prior to treatment, infiltrate must be cleared on repeat bone marrow aspirate

    Measured: Up to 10 years

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

    The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death.

    Measured: Duration of treatment (up to approximately 2 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Apr 2006 (estimated)
  2. Study startJun 2006
  3. Primary completionDec 2013
  4. Study completionJun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
151 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00310037
Sponsor's protocol ID
CALGB-50403
Other IDs
CDR0000466167
Status last verified
Oct 2025
First submitted
29 Mar 2006
Last updated
28 Oct 2025
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bortezomib in people with Mantle Cell Lymphoma, run by Alliance for Clinical Trials in Oncology at 48 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival Rate at 18 Months (time frame: At 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2025.

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