Rituximab, Combination Chemotherapy, and Bortezomib in Treating Patients With Untreated Mantle Cell Lymphoma - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00433537

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, 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.

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.

Condition	Intervention	Phase
Lymphoma	Biological: filgrastim Biological: pegfilgrastim Biological: rituximab Drug: bortezomib Drug: cyclophosphamide Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: vincristine sulfate	Phase II

Study Type:	Interventional
Study Design:	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 complete response [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Overall response rate [ Designated as safety issue: No ]
Progression-free survival (PFS) and overall survival (OS) [ Designated as safety issue: No ]
PFS and OS of patients who undergo autologous stem cell transplantation after induction therapy [ Designated as safety issue: No ]

Estimated Enrollment:	72
Study Start Date:	May 2007
Estimated Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the complete response rate in patients with untreated mantle cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, bortezomib, and dexamethasone (VcR-CVAD).

Secondary

Evaluate the overall response rate in patients treated with this regimen.
Evaluate the progression-free survival (PFS) and overall survival (OS) of patients treated with maintenance rituximab after VcR-CVAD induction therapy.
Evaluate the PFS and OS of patients who undergo autologous stem cell transplantation after VcR-CVAD induction therapy.
Evaluate the toxicity of this regimen in these patients.

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.

PROJECTED ACCRUAL: A total of 72 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 meeting ≥ 1 of the following criteria:
- Nuclear cyclin D1+ by immunohistochemistry
- t(11;14) by fluorescent in situ hybridization (FISH), polymerase chain reaction, or conventional karyotyping
Measurable disease by CT scan
No known CNS involvement

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Absolute neutrophil count > 1,500/mm^3 (unless low counts are due to marrow involvement or splenomegaly)
Platelet count > 100,000/mm^3 (unless low counts are due to marrow involvement or splenomegaly)
Creatinine < 2.0 mg/dL
Bilirubin < 2 mg/dL (≤ 3.0 mg/dL if due to Gilbert's disease or liver involvement by lymphoma)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
LVEF > 45% within the past 90 days (for patients > 45 years of age)
No known HIV positivity
No baseline peripheral neuropathy ≥ grade 2
No known hypersensitivity to boron or mannitol
No prior malignancy unless ≥ 1 of the following conditions are met:
- Malignancy was in situ
- Malignancy was treated surgically or with local external radiotherapy with curative intent and the patient has been disease free for > 3 years

PRIOR CONCURRENT THERAPY:

No prior chemotherapy, immunotherapy, or radiotherapy for mantle cell lymphoma
- Brief course (< 14 days) of steroid use for symptom relief or other indications allowed
At least 3 months since prior adjuvant hormonal therapy

Contacts and Locations

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

Show 165 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Brad S. Kahl, MD	University of Wisconsin, Madison
Investigator:	Mitchell R. Smith, MD, PhD	Fox Chase Cancer Center

More Information

Additional Information:

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

No publications provided

Responsible Party:	Robert L. Comis, ECOG Group Chair's Office
ClinicalTrials.gov Identifier:	NCT00433537 History of Changes
Other Study ID Numbers:	CDR0000528926, ECOG-E1405
Study First Received:	February 8, 2007
Last Updated:	April 14, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

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

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
Cyclophosphamide
Rituximab
Bortezomib
Dexamethasone
Doxorubicin
Vincristine

Lenograstim
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on February 09, 2012