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

NCT00711828 | Completed Phase 2 Results DMC

• 3 other identifiers: MC0883NCI-2011-02991P30CA015083
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial is studying how well giving rituximab and cyclophosphamide together with bortezomib and dexamethasone (R-CyBor-D) works in treating patients with relapsed or refractory low-grade follicular lymphoma, Waldenstrom macroglobulinemia, or 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. 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.

Conditions

Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Proportion of Responses (Complete Response or Partial Response)

  A response is defined to be a Complete Response (CR) or Partial Response (PR) noted as the objective status on any evaluation (i.e., best response). The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. A confidence interval for the true success proportion will be calculated according to the properties of the binomial distribution.

  up to 12 cycles

Secondary Outcomes (5)

• Overall Survival

  Up to 3 years from registration

• Progression-free Survival

  Up to 3 years from registration

• Duration of Response

  Up to 3 years from registration

• Time to Treatment Failure

  Up to 3 years from registration

• Adverse Events

  up to 12 cycles (28 days per cycle) of treatment

Study Arms (1)

Treatment (R-CYBOR-D)

EXPERIMENTAL

Patients receive rituximab IV on day 1and cyclophosphamide PO, bortezomib IV, and dexamethasone PO 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.

Drug: Bortezomib; Biological: Rituximab; Drug: Cyclophosphamide; Drug: Dexamethasone; Other: Questionnaire Administration; Other: Quality-of-Life Assessment

Interventions

Bortezomib DRUG

Given IV

Treatment (R-CYBOR-D)

Rituximab BIOLOGICAL

Given IV

Also known as: MOAB IDEC-C2B8

Treatment (R-CYBOR-D)

Cyclophosphamide DRUG

Given PO

Treatment (R-CYBOR-D)

Dexamethasone DRUG

Given PO

Also known as: DM

Treatment (R-CYBOR-D)

Questionnaire Administration OTHER

Complete a quality of life questionnaire (FACT/GOG neurotoxicity questionnaire, version 4.0)

Treatment (R-CYBOR-D)

Quality-of-Life Assessment OTHER

Complete a quality of life questionnaire (FACT/GOG neurotoxicity questionnaire, version 4.0)

Also known as: Quality of Life Assessment

Treatment (R-CYBOR-D)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological confirmation of relapsed or refractory follicular Grades 1 or 2 lymphoma, mantle cell lymphoma (MCL), small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, nodal marginal zone B-cell lymphoma, splenic marginal zone B-cell lymphoma, or lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia/WM) by biopsy ≤ 6 months prior to registration
• NOTE: MCL diagnosis should be confirmed by cyclin D1 staining or fluorescence in situ hybridization (FISH) (t(11;14))
• Measurable disease by computed tomography (CT), positron emission tomography (PET)/CT or magnetic resonance imaging (MRI) scans with lymph nodes ≥2.0 cm in at least one dimension or tumor cells in the blood ≥ 5 x10\^9/L
• NOTE: Lymphoplasmacytic lymphoma (WM) patients without lymphadenopathy must have 1.) \>10% lymphocytes, lymphoplasmacytic cells or plasma cells on a bone marrow aspirate/biopsy, and 2.) quantitative IgM ≥ 400mg/dL
• Expected survival \> 3 months
• ECOG Performance Status (PS) 0, 1 or 2
• Absolute Neutrophil Count ≥ 1200
• Platelet ≥ 75000
• Hemoglobin ≥ 8.0 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Alkaline phosphatase ≤ 3 x ULN
• Aspartate aminotransferase (AST) ≤ 3 x ULN
• Creatinine ≤ 1.5 x ULN
• Female subject is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of VELCADE (bortezomib), or agree to completely abstain from heterosexual intercourse
• Male subjects, even if surgically sterilized (i.e., status postvasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse

You may not qualify if:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant women -- confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women;
• Nursing women;
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse event of the prescribed regimen
• Patients known to be human immunodeficiency virus (HIV) positive
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Diagnosed or treated for another malignancy ≤ 3 years prior to registration, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy or low-risk prostate cancer after curative therapy
• NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
• Patient has received other investigational drugs ≤ 14 days prior to registration
• Patient has hypersensitivity to bortezomib, boron or mannitol
• Myocardial infarction ≤ 6 months prior to registration or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• NOTE: Prior to study entry, any electrocardiogram (ECG) abnormality at Screening has to be documented by the investigator as not medically relevant
• Previous cancer therapy, hormonal therapy and surgery \< 4 weeks prior to registration

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Waldenstrom Macroglobulinemia

Interventions

Bortezomib; Rituximab; Cyclophosphamide; Dexamethasone

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Craig B. Reeder, M.D.
• Organization: Mayo Clinic

Reeder.Craig@mayo.edu

Study Officials

• Craig Reeder

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2008
• First Posted: July 9, 2008
• Study Start: August 1, 2008
• Primary Completion: November 1, 2013
• Study Completion: April 6, 2018
• Last Updated: April 16, 2019
• Results First Posted: January 27, 2015

Record last verified: 2019-04

Locations

US (2)