S0601 Rituximab, Combination Chemotherapy, and Bortezomib Followed by Bortezomib Alone in Treating Patients With Newly Diagnosed Mantle Cell Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00376961
First received: September 13, 2006
Last updated: February 21, 2014
Last verified: February 2014
  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
Biological: rituximab
Drug: bortezomib
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisone
Drug: vincristine sulfate
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 2-year Progression-free Survival in Patients Treated With Rituximab-CHOP-bortezomib Induction Therapy (RCHOP-V) Followed by Bortezomib Maintenance Therapy (VM) [ Time Frame: 0-2 years ] [ Designated as safety issue: No ]
    Measured from date of registration to date of first observation of relapsed or progressive disease, or death due to any cause.


Secondary Outcome Measures:
  • Response Rate in Patients Treated With Rituximab-CHOPbortezomib Induction Therapy (R-CHOP-V) Followed by Bortezomib Maintenance Therapy(VM). [ Time Frame: At the time of restaging (between Cycles 6 and 7), every 6 months during Cycles 7-14, and at the end of protocol treatment ] [ Designated as safety issue: No ]
    Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.

  • 2-year Overall Survival in Patients Treated With Rituximab-CHOP-bortezomib Induction Therapy (RCHOP-V) Followed by Bortezomib Maintenance Therapy (VM) [ Time Frame: 0-2 years ] [ Designated as safety issue: No ]
    Measured from date of registration to date of death due to any cause or last contact

  • Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [ Time Frame: Assessed prior to each cycle (for Cycles 2-6), at restaging (between Cycle 6 and 7), every 3 months ( for Cycle 7-14), and at the end of protocol treatment. ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.


Enrollment: 68
Study Start Date: August 2006
Estimated Study Completion Date: October 2015
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: R-CHOP + Velcade
6 21-day cycles of standard R-CHOP with 1.3 mg/m^2 Bortezomib given on days 1 and 4 of each cycle. This is followed by 8 3-month cycles of maintenance with 1.3 mg/m^2 Bortezomib on days 1, 4, 8 and 11 of each cycle.
Biological: rituximab
375 mg/m^2 on day 1 for cycles 1-6.
Other Name: Rituxan
Drug: bortezomib
1.3 mg/m^2 on days 1, 4 of cycles 1-6 and on days 1, 4, 8, 11 of cycles 7-14.
Other Name: Velcade
Drug: cyclophosphamide
750 mg/m^2 on day 1 of cycles 1-6.
Drug: doxorubicin hydrochloride
50 mg/m^2 on day 1 of cycles 1-6.
Drug: prednisone
100 mg on days 1-5 of cycles 1-6.
Drug: vincristine sulfate
1.4 mg/m^2 on day 1 of cycles 1-6.

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:

      • Cluster of differentiation antigen 19 (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 central nervous system (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
Investigators
Study Chair: Steven H. Bernstein, MD James P. Wilmot Cancer Center
Study Chair: Richard I. Fisher, MD James P. Wilmot Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00376961     History of Changes
Other Study ID Numbers: CDR0000494646, U10CA032102, S0601
Study First Received: September 13, 2006
Results First Received: January 2, 2013
Last Updated: February 21, 2014
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
contiguous stage II mantle cell lymphoma
noncontiguous stage II 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
Doxorubicin
Prednisone
Vincristine
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
Antibiotics, Antineoplastic
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on April 17, 2014