Bortezomib, Rituximab, Cyclophosphamide, and Prednisone in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

NCT00295932 | Completed Phase 1 Results

• 2 other identifiers: 05-103MSKCC-05103
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 8

Brief Summary

RATIONALE: 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 prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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. Giving bortezomib together with cyclophosphamide, prednisone, and rituximab may be an effective treatment for non-Hodgkin's lymphoma. PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of bortezomib when given together with cyclophosphamide, prednisone, and rituximab and to see how well it works in treating patients with relapsed or refractory indolent B-cell non-Hodgkin's lymphoma.

Conditions

Leukemia; Lymphoma

Keywords

recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent small lymphocytic lymphoma; recurrent marginal zone lymphoma; Waldenstrom macroglobulinemia; recurrent mantle cell lymphoma; refractory chronic lymphocytic leukemia; B-cell chronic lymphocytic leukemia; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  Maximum tolerated dose of Bortezomib in combination with Rituximab, Cyclophosphamide and Prednisone in Phase I participants

  2 years

Secondary Outcomes (5)

• Progression-free Survival

  2 years

• Duration of Response (Mean and Median)

  2 years

• Event-free Survival

  2 years

• Overall Survival

  2 years

• Toxicity of Participants Receiving Bortezomib, Rituximab, Cyclophosphamide, and Prednisone for Treatment of Non-Hodgkin's Lymphoma

  2 years

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2, 5, 9, and 12. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Biological: rituximab; Drug: bortezomib; Drug: cyclophosphamide; Drug: prednisone

Arm II

EXPERIMENTAL

Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Biological: rituximab; Drug: bortezomib; Drug: cyclophosphamide; Drug: prednisone

Interventions

rituximab BIOLOGICAL

Given IV

Arm I; Arm II

bortezomib DRUG

Given IV

Arm I; Arm II

cyclophosphamide DRUG

Given IV

Arm I; Arm II

prednisone DRUG

Given orally

Arm I; Arm II

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed diagnosis of 1 of the following: * Chronic lymphocytic leukemia (CLL) * B-cell small lymphocytic leukemia (SLL) * Any marginal zone lymphoma * Grade 1-3A follicular lymphoma * Waldenstrom's macroglobulinemia * Mantle cell lymphoma * No transformed indolent lymphoma * Assessable disease (phase I) * Measurable disease (phase I and II), defined as ≥ one lesion that can be accurately measured in ≥ 1 dimension as ≥ 2 cm by conventional techniques OR ≥ 1 cm by spiral CT scan * Lymph nodes measuring ≤ 1 cm in the short axis are considered normal * Relapsed or refractory disease * Must have received at least 1 prior therapeutic regimen but no more than 3 prior conventional cytotoxic therapy regimens * No known brain metastases or meningeal disease PATIENT CHARACTERISTICS: * Karnofsky performance status \> 50% * Absolute neutrophil count \> 1,000/mcl (more than 500/mcl if known lymphomatous involvement) * Platelet count ≥ 50,000/mcl * Total bilirubin \< 1.5 times upper limit of normal (ULN) (less than 5 mg/dL if known history of Gilbert's disease) * AST and ALT ≤ 2.5 times ULN (4 times ULN if liver involvement) * Creatinine \< 1.5 times ULN OR creatinine clearance \> 50 mL/min * Patients may have febrile episodes up to 38.5ºC without evidence of active infection * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No New York Heart Association class III or IV congestive heart failure * No uncontrolled intercurrent illness, including any of the following: * Ongoing or active infection * Cerebrovascular accident or transient ischemic attack within 6 months of study entry * Unstable angina pectoris * Cardiac arrhythmia * EKG evidence of acute ischemia * Psychiatric illness/social situations that would limit compliance with study requirements * No uncontrolled hypertension requiring active manipulation of antihypertensive medications * No known or active HIV infection * No history of hypersensitivity to bortezomib, boron, or mannitol * No peripheral neuropathy \> grade 2 * No other malignancy within the past 5 years except curatively treated non life-threatening malignancies, such as cutaneous basal cell or squamous cell carcinoma or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from prior therapy * Prior stem cell transplantation allowed * Preparative cytoreductive and high-dose therapies considered 1 prior therapy * At least 4 weeks since prior cytotoxic chemotherapy (6 weeks since prior nitrosoureas or mitomycin C) * At least 12 weeks since prior radioimmunotherapy * One prior course comprising tositumomab or ibritumomab tiuxetan allowed * At least 1 week since prior palliative steroids for NHL * No therapeutic monoclonal antibodies (e.g., rituximab, tositumomab, ibritumomab, alemtuzumab, etc.) within 3 months of study entry * Patients treated with monoclonal antibodies within 3 months allowed provided disease progressed on this therapy AND no treatment received 7 days prior to study entry * Seven days since prior rituximab (for patients enrolled in phase I portion) * No major surgery within 4 weeks of study entry * No other concurrent investigational agents * No other concurrent anticancer therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Rutgers Cancer Institute of New Jersey: collaborator
• Columbia University: collaborator
• Emory University: collaborator

Study Sites (8)

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Memorial Sloan-Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08903, United States

Location

Memorial Sloan-Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan-Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Location

Memoral Sloan Kettering Cancer Center@Phelps

Sleepy Hollow, New York, United States

Location

Related Publications (1)

• Gerecitano J, Portlock C, Hamlin P, Moskowitz CH, Noy A, Straus D, Schulman P, Dumitrescu O, Sarasohn D, Pappanicholaou J, Iasonos A, Zhang Z, Mo Q, Horanlli E, Rojas CN, Zelenetz AD, O'Connor OA. Phase I trial of weekly and twice-weekly bortezomib with rituximab, cyclophosphamide, and prednisone in relapsed or refractory non-Hodgkin lymphoma. Clin Cancer Res. 2011 Apr 15;17(8):2493-501. doi: 10.1158/1078-0432.CCR-10-1498. Epub 2011 Feb 23.

  PMID: 21346146 RESULT

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

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

Interventions

Rituximab; Bortezomib; Cyclophosphamide; Prednisone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Analysis available and entered in the results section for Phase I participants. Cannot submit results on Phase II because analysis was incomplete when PI left MSK.

Results Point of Contact

• Title: Dr. Carol Portlock
• Organization: Memorial Sloan Kettering Cancer Center

portlocc@mskcc.org

212-639-8109

Study Officials

• Carol Portlock, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2006
• First Posted: February 24, 2006
• Study Start: December 13, 2005
• Primary Completion: March 11, 2018
• Study Completion: March 11, 2018
• Last Updated: November 20, 2018
• Results First Posted: November 20, 2018

Record last verified: 2018-03

Locations

US (8)