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| Sponsor: | Memorial Sloan-Kettering Cancer Center |
|---|---|
| Collaborator: |
National Cancer Institute (NCI) |
| Information provided by: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00295932 |
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia Lymphoma |
Biological: rituximab Drug: bortezomib Drug: cyclophosphamide Drug: prednisone |
Phase I Phase II |
| Study Type: | Interventional |
| Study Design: | Treatment, Randomized, Open Label |
| Official Title: | A Phase I/II Study of the Novel Proteasome Inhibitor Bortezomib in Combination With Rituximab, Cyclophosphamide and Prednisone in Patients With Relapsed/Refractory Indolent B-Cell Lymphoproliferative Disorders and Mantle Cell Lymphoma (MCL) |
| Estimated Enrollment: | 115 |
| Study Start Date: | December 2005 |
| Estimated Primary Completion Date: | September 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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
Given IV
Drug: bortezomib
Given IV
Drug: cyclophosphamide
Given IV
Drug: prednisone
Given orally
|
|
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
Given IV
Drug: bortezomib
Given IV
Drug: cyclophosphamide
Given IV
Drug: prednisone
Given orally
|
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a phase I dose-escalation study of bortezomib followed by a phase II randomized, multicenter study. Patients in phase II are stratified according to disease (mantle cell lymphoma vs indolent B-cell lymphoproliferative disorder vs transformed lymphoma).
Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Phase II (patients with follicular lymphoma only): Patients are randomized to 1 of 2 treatment arms.
After completion of study treatment, patients are followed at 1 month, every 4 months for 2 years, and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 115 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 |
DISEASE CHARACTERISTICS:
Histologically confirmed diagnosis of 1 of the following:
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
Relapsed or refractory disease
PATIENT CHARACTERISTICS:
No uncontrolled intercurrent illness, including any of the following:
PRIOR CONCURRENT THERAPY:
Prior stem cell transplantation allowed
At least 12 weeks since prior radioimmunotherapy
No therapeutic monoclonal antibodies (e.g., rituximab, tositumomab, ibritumomab, alemtuzumab, etc.) within 3 months of study entry
Contacts and Locations| United States, New York | |
| Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center | Recruiting |
| New York, New York, United States, 10032 | |
| Contact: Clinical Trials Office - Herbert Irving Comprehensive Cancer C 212-305-8615 | |
| Memorial Sloan-Kettering Cancer Center | Recruiting |
| New York, New York, United States, 10065 | |
| Contact: John F. Gerecitano, MD, PhD 212-639-3748 gerecitj@mskcc.org | |
| Study Chair: | John F. Gerecitano, MD, PhD | Memorial Sloan-Kettering Cancer Center |
More Information
| Responsible Party: | Memorial Sloan-Kettering Cancer Center ( John F. Gerecitano ) |
| Study ID Numbers: | CDR0000456444, MSKCC-05103 |
| Study First Received: | February 23, 2006 |
| Last Updated: | July 7, 2009 |
| ClinicalTrials.gov Identifier: | NCT00295932 History of Changes |
| Health Authority: | Unspecified |
|
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 |
|
Anti-Inflammatory Agents Prednisone Immunologic Factors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Lymphoma, Mantle-Cell Physiological Effects of Drugs Hormones, Hormone Substitutes, and Hormone Antagonists Cyclophosphamide Hormones Leukemia Therapeutic Uses Lymphoma Alkylating Agents Immunoproliferative Disorders |
Neoplasms by Histologic Type Antineoplastic Agents, Hormonal Immune System Diseases Rituximab Bortezomib Enzyme Inhibitors Glucocorticoids Immunosuppressive Agents Pharmacologic Actions Protease Inhibitors Lymphatic Diseases Neoplasms Myeloablative Agonists Antineoplastic Agents, Alkylating Lymphoproliferative Disorders |