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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00433537
First received: February 8, 2007
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: bortezomib
Biological: rituximab
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
Drug: dexamethasone
Biological: filgrastim
Biological: pegfilgrastim
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of VcR-CVAD With Rituximab Maintenance for Untreated Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall response rate [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Reported along with the 90% confidence interval.

  • Progression-free survival [ Time Frame: From entry onto study until lymphoma progression or death form any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.

  • Overall survival [ Time Frame: The date of study entry to the date of death, assessed up to 10 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.


Estimated Enrollment: 72
Study Start Date: May 2007
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (combination chemotherapy, rituximab)

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

Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: dexamethasone
Given IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Biological: pegfilgrastim
Given SC
Other Names:
  • Filgrastim SD-01
  • GCSF-SD01
  • Neulasta
  • SD-01 sustained duration G-CSF
Other: laboratory biomarker analysis
Correlative studies

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00433537

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Investigators
Principal Investigator: Brad Kahl Eastern Cooperative Oncology Group
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00433537     History of Changes
Other Study ID Numbers: NCI-2012-02966, E1405, ECOG-E1405, U10CA021115
Study First Received: February 8, 2007
Last Updated: July 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Antibodies, Monoclonal
Cyclophosphamide
Lenograstim
Rituximab
Bortezomib
Dexamethasone
Doxorubicin
Vincristine
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 22, 2014