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Contiguous Stage II Mantle Cell LymphomaPhase 2NCT00433537

Combination Chemotherapy and Rituximab in Treating Patients With Untreated Mantle Cell Lymphoma

A Phase 2 study testing bortezomib, rituximab and cyclophosphamide in people with Contiguous Stage II Mantle Cell Lymphoma and Noncontiguous Stage II Mantle Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site 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 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
bortezomib, rituximab and cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
1 siteUnited States
Study dates
May 2007to Jun 2013
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Eastern Cooperative Oncology Group

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Phase II Study of VcR-CVAD With Rituximab Maintenance for Untreated Mantle Cell Lymphoma

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).

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the complete response (CR) rate in patients with mantle cell lymphoma, who are treated with VcR-CVAD.

SECONDARY OBJECTIVES:

  1. To evaluate the overall response rate to VcR-CVAD. II. To evaluate the progression-free survival (PFS) and overall survival (OS) of patients receiving maintenance rituximab after VcR-CVAD induction.

III. To evaluate the PFS and OS of patients who receive autologous stem cell transplantation (ASCT) after VcR-CVAD induction.

IV. To evaluate the toxicity of VcR-CVAD.

TERTIARY OBJECTIVES:

  1. Evaluation of antigen expression patterns to determine or confirm possible unique expressions of MCL.

II. To evaluate the percentage of circulating mantle cell lymphoma (MCL) cells.

OUTLINE: This is a multicenter study.

Induction therapy (VcR-CVAD): Patients receive VcR-CVAD comprising bortezomib 1.3 mg/m2 IV over 3-5 seconds on days 1 and 4; rituximab 375 mg/m2 IV over 3-4 hours on day 1; doxorubicin hydrochloride 25 mg/m2/d IV over 48 hours on days 1 and 2; cyclophosphamide 300 mg/m2 IV over 3 hours every 12 hours on days 1-3; vincristine 1 mg IV over 3-5 seconds on day 3; and dexamethasone 40 mg 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 (ASCT) (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.

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.

  • bortezomibDrug

    Also called LDP 341, MLN341, VELCADE

    Given IV

  • rituximabBiological

    Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8

    Given IV

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • doxorubicin hydrochlorideDrug

    Also called ADM, ADR, Adria, Adriamycin PFS

    Given IV

  • vincristineDrug

    Also called Vincristine sulfate, Leurocristine sulfate, VCR, Vincasar PFS

    Given IV

  • dexamethasoneDrug

    Also called Aeroseb-Dex, Decaderm, Decadron, DM

    Given IV

  • filgrastimBiological

    Also called G-CSF, Neupogen

    Given SC

  • pegfilgrastimBiological

    Also called Filgrastim SD-01, GCSF-SD01, Neulasta, SD-01 sustained duration G-CSF

    Given SC

  • Autologous stem cell transplantation (ASCT)Procedure or surgery

Study groups in NCT00433537
Study groupRoleWhat they receive
VcR-CVAD induction followed by maintenance rituximabExperimentalVcR-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.
Receives: Drug: bortezomib; Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: vincristine; Drug: dexamethasone; Biological: filgrastim; Biological: pegfilgrastim
VcR-CVAD induction followed by ASCTExperimentalVcR-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.
Receives: Drug: bortezomib; Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: vincristine; Drug: dexamethasone; Biological: filgrastim; Biological: pegfilgrastim; Procedure: Autologous stem cell transplantation (ASCT)

What is being measured

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

  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.

    Measured: Assessed after VcR-CVAD cycles 2, 4, and 6.

Secondary outcomes (2)

  1. 2-year Progression-free Survival (PFS)

    PFS for patients who received maintenance rituximab or ASCT after VcR-CVAD induction is defined as time from start of maintenance rituximab or ASCT to earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored.

    Measured: Assessed every 6 months for 5 years, and then yearly thereafter.

  2. 3-year Overall Survival (OS)

    OS for patients who received maintenance rituximab or ASCT after VcR-CVAD induction is defined as time from start of maintenance rituximab or ASCT to death. Patients alive at last follow-up were censored.

    Measured: Assessed every 6 months for 5 years, and then yearly thereafter.

Timeline

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

  1. First posted12 Feb 2007 (estimated)
  2. Study startMay 2007
  3. Primary completionJun 2013
  4. Study completionJun 2013

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00433537
Sponsor's protocol ID
NCI-2012-02966
Other IDs
NCI-2012-02966, E1405, E1405, E1405, U10CA021115
Status last verified
Jan 2014
First submitted
8 Feb 2007
Last updated
30 Oct 2014
Data monitoring committee
No

Publications

  • 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.

    PubMed 24458437

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bortezomib, rituximab and cyclophosphamide in people with Contiguous Stage II Mantle Cell Lymphoma and Noncontiguous Stage II Mantle Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site 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?

The sponsor lists 10 inclusion and 9 exclusion criteria. 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 30 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 30 Oct 2014). 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?

Complete Response (CR) Rate (time frame: Assessed after VcR-CVAD cycles 2, 4, and 6.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00433537, which also lists 1 linked publication.

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 30 Oct 2014.

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