Rituximab, Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Low-Grade Follicular Lymphoma, Waldenstrom Macroglobulinemia, or Mantle Cell Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00711828
First received: July 8, 2008
Last updated: May 1, 2014
Last verified: May 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. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab and bortezomib together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab and cyclophosphamide together with bortezomib and dexamethasone works in treating patients with relapsed or refractory low-grade follicular lymphoma, Waldenstrom macroglobulinemia, or mantle cell lymphoma.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Drug: bortezomib
Drug: cyclophosphamide
Drug: dexamethasone
Other: questionnaire administration
Procedure: quality-of-life assessment
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Clinical Trial of Rituximab, Cyclophosphamide, Bortezomib (VELCADE®), and Dexamethasone (R-CyBor-D) in Relapsed Low Grade and Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Proportion of responses (complete response or partial response) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Time to treatment failure [ Designated as safety issue: No ]
  • Adverse events [ Designated as safety issue: Yes ]

Estimated Enrollment: 36
Study Start Date: October 2008
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To assess tumor response in patients with relapsed or refractory low-grade follicular lymphoma (grade I or II), mantle cell lymphoma, or lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia) treated with rituximab, cyclophosphamide, bortezomib, and dexamethasone.

Secondary

  • To evaluate overall survival, progression-free survival, duration of response, and time to treatment failure in patients treated with this regimen.
  • To describe the adverse event profile (as assessed by NCI CTCAE version 3.0) of this regimen in these patients.
  • To evaluate the quality of life, in terms of patient-reported neurotoxicity, in patients treated with this regimen.

OUTLINE: Patients receive rituximab IV on day 1, bortezomib IV on days 1, 4, 8, and 11, and oral cyclophosphamide and oral dexamethasone on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Patients complete a quality of life questionnaire (FACT/GOG neurotoxicity questionnaire, version 4.0) at baseline, on day 1 of courses 3, 6, and 9, and at the completion of study treatment.

After completion of study treatment, patients are followed every 3-6 months for up to 5 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed relapsed or refractory follicular lymphoma (grade I or II), mantle cell lymphoma (MCL), or lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia [WM])

    • MCL confirmed by cyclin D1 staining or fluorescent in situ hybridization [t(11;14)]
  • Measurable disease, defined as lymph nodes ≥ 2.0 cm in at least one dimension by CT scan, PET/CT scan, or MRI

    • Patients with WM without lymphadenopathy must have > 10% lymphocytes, lymphoplasmacytic cells, or plasma cells on a bone marrow aspirate/biopsy AND quantitative IgM ≥ 400 mg/dL

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy > 3 months
  • ANC ≥ 1,200/mm^3
  • Platelet count ≥ 75,000/mm^3
  • Hemoglobin ≥ 8.0 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin ≤ 2.0 mg/dL
  • Alkaline phosphatase ≤ 3 times ULN
  • AST ≤ 3 times ULN
  • Creatinine ≤ 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No comorbid systemic illness or other severe concurrent disease that, in the judgment of the investigator, would exclude the patient from participating in this study or would interfere significantly with the proper assessment of safety and adverse events of the prescribed study regimen
  • No known HIV positivity
  • No concurrent uncontrolled illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable or uncontrolled angina pectoris
    • Cardiac arrhythmias, including severe uncontrolled ventricular arrhythmias
    • Psychiatric illness/social situation that would preclude compliance with study requirements
  • No hypersensitivity to bortezomib, boron, or mannitol
  • No myocardial infarction within the past 6 months
  • No NYHA class III-IV heart failure
  • No evidence of acute ischemia by ECG
  • No active conduction system abnormalities
  • No other malignancy within the past 3 years, except for the following:

    • Completely resected basal cell or squamous cell carcinoma of the skin
    • In situ malignancy
    • Curatively treated prostate cancer deemed to be at low risk

PRIOR CONCURRENT THERAPY:

  • More than 14 days since prior investigational drugs
  • At least 4 weeks since prior anticancer therapy, including radiotherapy, hormonal therapy, or surgery
  • No other concurrent investigational agents as treatment for the primary malignancy
  • No concurrent therapy for other malignancies, except hormonal therapy
  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: NCT00711828

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259-5499
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Craig B. Reeder, M.D. Mayo Clinic
Principal Investigator: Thomas E. Witzig, M.D. Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Craig B. Reeder, Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT00711828     History of Changes
Other Study ID Numbers: MC0883, P30CA015083, MC0883, 08-001490
Study First Received: July 8, 2008
Last Updated: May 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent mantle cell lymphoma
Waldenstrom macroglobulinemia

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Waldenstrom Macroglobulinemia
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Cyclophosphamide
Rituximab
Bortezomib
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014