Rituximab, Combination Chemotherapy, and Bortezomib Followed by Bortezomib Alone in Treating Patients With Newly Diagnosed Mantle Cell Lymphoma - Full Text View

Sponsors and Collaborators:	Southwest Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00376961

Purpose

RATIONALE: 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 work in different ways to stop the growth of cancer cells, either by killing the cells or by 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. Giving bortezomib as maintenance therapy may keep the cancer from progressing.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy and bortezomib followed by bortezomib alone works in treating patients with newly diagnosed mantle cell lymphoma.

Condition	Intervention	Phase
Lymphoma	Drug: bortezomib Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: rituximab Drug: vincristine sulfate	Phase II

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Prednisone Vincristine sulfate Vincristine Rituximab Bortezomib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Study of Combination Rituximab-CHOP and Bortezomib (Velcade®) (R-CHOP-V) Induction Therapy Followed by Bortezomib Maintenance (VM) Therapy for Patients With Newly Diagnosed Mantle Cell Lymphoma

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

Primary Outcome Measures:

Progression-free survival rate at 2 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rate (complete, complete unconfirmed, and partial responses) [ Designated as safety issue: No ]
Toxicity of bortezomib maintenance therapy assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	August 2006
Estimated Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the 2-year progression-free survival rate in patients with newly diagnosed mantle cell lymphoma treated with induction therapy comprising rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone, and bortezomib followed by bortezomib maintenance (VM) therapy.

Secondary

Determine the response rate (complete, complete unconfirmed, and partial responses) in patients treated with this regimen.
Determine the toxicity of VM in these patients.

OUTLINE: This is a multicenter study.

Induction therapy: Patients receive R-CHOP-V induction therapy comprising rituximab IV over ≤ 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin hydrochloride IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1; oral prednisone once daily on days 1-5; and bortezomib IV over 30-90 minutes on days 1 and 4. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with stable disease or better proceed to bortezomib maintenance therapy.
Maintenance therapy: Beginning 3 months after completion of R-CHOP-V induction therapy, patients receive bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 3 months for up to 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 4 years and then annually for 3 years.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed mantle cell lymphoma (MCL) meeting the following criteria:
- Stage III-IV or bulky stage II disease
- Confirmation of positivity for the following phenotypes by immunohistochemistry or flow cytometry:
  - CD19 (or CD20)
  - Cyclin D1 OR evidence of t(11;14) translocation by cytogenetic analysis or fluorescent in situ hybridization
Newly diagnosed, previously untreated disease
Bidimensionally measurable disease by conventional techniques
- No nonmeasurable disease only
Adequate tumor tissue from original diagnostic specimen available
- Tissue obtained by needle aspiration or cytology not allowed
No clinical evidence of CNS involvement by lymphoma
Co-registration on protocols SWOG-8947 and SWOG-8819 is strongly encouraged

PATIENT CHARACTERISTICS:

Zubrod performance status 0-2
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No peripheral neuropathy ≥ grade 2
No hypersensitivity to bortezomib, boron, or mannitol
No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer for which the patient is currently in complete remission, or any other cancer for which the patient has been disease free for the past 5 years
HIV negative

PRIOR CONCURRENT THERAPY:

No prior chemotherapy, radiotherapy, or antibody therapy for lymphoma
More than 14 days since prior investigational drugs

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00376961

Show 147 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Steven H. Bernstein, MD	James P. Wilmot Cancer Center
Investigator:	Richard I. Fisher, MD	James P. Wilmot Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000494646, SWOG-S0601
Study First Received:	September 13, 2006
Last Updated:	January 13, 2009
ClinicalTrials.gov Identifier:	NCT00376961
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma

Study placed in the following topic categories:

Prednisone
Immunoproliferative Disorders
Rituximab
Lymphoma, Mantle-Cell
Bortezomib
Vincristine
Cyclophosphamide

Mantle cell lymphoma
Doxorubicin
Lymphatic Diseases
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antibiotics, Antineoplastic
Hormones
Therapeutic Uses
Alkylating Agents
Neoplasms by Histologic Type
Immune System Diseases
Antineoplastic Agents, Hormonal

Mitosis Modulators
Enzyme Inhibitors
Antimitotic Agents
Immunosuppressive Agents
Glucocorticoids
Pharmacologic Actions
Protease Inhibitors
Neoplasms
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 15, 2009