- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00335140
Rituximab and Combination Chemotherapy in Treating Patients With Primary Central Nervous System Lymphoma
Phase II Study of Rituximab Given in Conjunction With Standard Chemotherapy in Primary Central Nervous System (CNS) Lymphoma
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as methotrexate, leucovorin, vincristine, procarbazine, dexamethasone, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with primary central nervous system (CNS) lymphoma.
Study Overview
Status
Conditions
Detailed Description
OBJECTIVES:
Primary
- Determine the complete response rate.
Secondary
- Determine the progression-free survival of these patients.
- Determine the proportion of progression-free and overall survival in these patients.
- Determine rituximab cerebrospinal fluid pharmacokinetics (only in patients requiring intrathecal chemotherapy).
OUTLINE: This is a multicenter study.
Patients receive rituximab IV 3 times weekly in weeks 1-4; high-dose methotrexate IV over 2 hours in weeks 1, 3, 5, and 9; oral or IV leucovorin calcium every 6 hours for 12 doses beginning 24 hours after the start of methotrexate in weeks 1, 3, 5, and 9; vincristine IV in weeks 1, 3, 5, 7, and 9; oral procarbazine hydrochloride daily on days 1-7 in weeks 1, 5, and 9; oral dexamethasone daily in weeks 1-6; and cytarabine IV over 2 hours twice weekly in weeks 11 and 14.
Patients with positive cerebrospinal fluid also receive methotrexate intrathecally and oral leucovorin calcium every 12 hours for 8 doses beginning 24 hours after the start of methotrexate in weeks 2, 4, 6, 8, and 10.
After completion of study treatment, patients are followed periodically for 5 years.
PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Stanford, California, United States, 94305-5824
- Stanford Cancer Center
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Florida
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Gainesville, Florida, United States, 32610-0232
- University of Florida Shands Cancer Center
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Jacksonville, Florida, United States, 32224
- Mayo Clinic - Jacksonville
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Illinois
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Chicago, Illinois, United States, 60612-3785
- John H. Stroger, Jr. Hospital of Cook County
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Hinsdale, Illinois, United States, 60521
- Hinsdale Hematology Oncology Associates
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Iowa
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Ames, Iowa, United States, 50010
- McFarland Clinic, PC
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Sioux City, Iowa, United States, 51101
- Siouxland Hematology-Oncology Associates, LLP
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Sioux City, Iowa, United States, 51104
- St. Luke's Regional Medical Center
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Sioux City, Iowa, United States, 51104
- Mercy Medical Center - Sioux City
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Kansas
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Anthony, Kansas, United States, 67003
- Hospital District Sixth of Harper County
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Chanute, Kansas, United States, 66720
- Cancer Center of Kansas, PA - Chanute
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Dodge City, Kansas, United States, 67801
- Cancer Center of Kansas, PA - Dodge City
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El Dorado, Kansas, United States, 67042
- Cancer Center of Kansas, PA - El Dorado
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Fort Scott, Kansas, United States, 66701
- Cancer Center of Kansas - Fort Scott
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Independence, Kansas, United States, 67301
- Cancer Center of Kansas-Independence
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Kingman, Kansas, United States, 67068
- Cancer Center of Kansas, PA - Kingman
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Lawrence, Kansas, United States, 66044
- Lawrence Memorial Hospital
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Liberal, Kansas, United States, 67901
- Southwest Medical Center
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Newton, Kansas, United States, 67114
- Cancer Center of Kansas, PA - Newton
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Parsons, Kansas, United States, 67357
- Cancer Center of Kansas, PA - Parsons
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Pratt, Kansas, United States, 67124
- Cancer Center of Kansas, PA - Pratt
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Salina, Kansas, United States, 67042
- Cancer Center of Kansas, PA - Salina
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Wellington, Kansas, United States, 67152
- Cancer Center of Kansas, PA - Wellington
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Wichita, Kansas, United States, 67214
- Wesley Medical Center
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Wichita, Kansas, United States, 67208
- Cancer Center of Kansas, PA - Medical Arts Tower
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Wichita, Kansas, United States, 67214
- Cancer Center of Kansas, PA - Wichita
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Wichita, Kansas, United States, 67214
- CCOP - Wichita
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Wichita, Kansas, United States, 67214
- Via Christi Cancer Center at Via Christi Regional Medical Center
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Wichita, Kansas, United States, 67208
- Associates in Womens Health, PA - North Review
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Winfield, Kansas, United States, 67156
- Cancer Center of Kansas, PA - Winfield
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Maryland
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Baltimore, Maryland, United States, 21231-2410
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Michigan
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Kalamazoo, Michigan, United States, 49007
- Bronson Methodist Hospital
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Kalamazoo, Michigan, United States, 49001
- Borgess Medical Center
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Kalamazoo, Michigan, United States, 49007-3731
- West Michigan Cancer Center
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Minnesota
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Burnsville, Minnesota, United States, 55337
- Fairview Ridges Hospital
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Coon Rapids, Minnesota, United States, 55433
- Mercy and Unity Cancer Center at Mercy Hospital
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Edina, Minnesota, United States, 55435
- Fairview Southdale Hospital
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Fridley, Minnesota, United States, 55432
- Mercy and Unity Cancer Center at Unity Hospital
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Hutchinson, Minnesota, United States, 55350
- Hutchinson Area Health Care
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Maplewood, Minnesota, United States, 55109
- Minnesota Oncology Hematology, PA - Maplewood
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Maplewood, Minnesota, United States, 55109
- HealthEast Cancer Care at St. John's Hospital
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Minneapolis, Minnesota, United States, 55407
- Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
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Minneapolis, Minnesota, United States, 55415
- Hennepin County Medical Center - Minneapolis
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Robbinsdale, Minnesota, United States, 55422-2900
- Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
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Rochester, Minnesota, United States, 55905
- Mayo Clinic Cancer Center
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Saint Louis Park, Minnesota, United States, 55416
- CCOP - Metro-Minnesota
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Saint Louis Park, Minnesota, United States, 55416
- Park Nicollet Cancer Center
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Saint Paul, Minnesota, United States, 55102
- United Hospital
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Saint Paul, Minnesota, United States, 55101
- Regions Hospital Cancer Care Center
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Shakopee, Minnesota, United States, 55379
- St. Francis Cancer Center at St. Francis Medical Center
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Waconia, Minnesota, United States, 55387
- Ridgeview Medical Center
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Woodbury, Minnesota, United States, 55125
- Minnesota Oncology Hematology, PA - Woodbury
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Ohio
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Akron, Ohio, United States, 44309-2090
- Summa Center for Cancer Care at Akron City Hospital
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Barberton, Ohio, United States, 44203
- Barberton Citizens Hospital
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Canton, Ohio, United States, 44710-1799
- Aultman Cancer Center at Aultman Hospital
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Cleveland, Ohio, United States, 44109
- MetroHealth Cancer Care Center at MetroHealth Medical Center
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Pennsylvania
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Allentown, Pennsylvania, United States, 18105
- Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
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Danville, Pennsylvania, United States, 17822-0001
- Geisinger Cancer Institute at Geisinger Health
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Hazleton, Pennsylvania, United States, 18201
- Geisinger Hazleton Cancer Center
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Philadelphia, Pennsylvania, United States, 19111-2497
- Fox Chase Cancer Center - Philadelphia
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State College, Pennsylvania, United States, 16801
- Geisinger Medical Group - Scenery Park
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Wilkes-Barre, Pennsylvania, United States, 18711
- Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
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South Dakota
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Sioux Falls, South Dakota, United States, 57105
- Medical X-Ray Center, PC
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Sioux Falls, South Dakota, United States, 57117-5039
- Sanford Cancer Center at Sanford USD Medical Center
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Tennessee
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Nashville, Tennessee, United States, 37232-6838
- Vanderbilt-Ingram Cancer Center
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West Virginia
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Charleston, West Virginia, United States, 25304
- West Virginia University Health Sciences Center - Charleston
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Wisconsin
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La Crosse, Wisconsin, United States, 54601
- Gundersen Lutheran Center for Cancer and Blood
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Madison, Wisconsin, United States, 53792-6164
- University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion criteria:
- Histologically confirmed non-Hodgkin's lymphoma by brain biopsy
Patients with inconclusive biopsy or patients who are not candidates for biopsy must have typical CT scan or MRI of the brain AND meet ≥ 1 of the following criteria:
- Positive cerebrospinal fluid cytology for lymphoma OR a monoclonal lymphoid population as defined by cell surface markers or immunoglobulin gene rearrangement studies
- Biopsy-proven involvement of the vitreous or uvea if cells are apparent in the posterior chamber or vitreous by ophthalmological examination
Bideminsionally measurable disease, defined as contrast-enhancing tumor ≥ 1 cm by pretreatment MRI/CT scan
- Meningeal or vitreous involvement constitutes evaluable but not measurable disease
- If an excisional, rather than a needle biopsy was done, measurable disease must be present on a postoperative scan (not a PET-CT scan)
- ECOG performance status 0-3
- Absolute granulocyte count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ upper limit of normal (ULN)
- SGOT ≤ 2.0 times ULN
- Creatinine clearance ≥ 50 mL/min
- Negative pregnancy test
- Fertile patients must use effective contraception
Exclusion criteria:
- Pregnant or nursing
- HIV-1 positivity
- Other malignancy within the past 5 years except basal cell skin cancer or any carcinoma in situ
- Pre-existing immunodeficiency
- Hepatitis B surface antigen positivity
- Systemic lymphoma (as determined by pre-registration CT scans and physical examination)
- Prior chemotherapy or radiotherapy for primary central nervous system lymphoma
- Prior organ or bone marrow transplantation
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Rituximab + standard chemotherapy
Rituximab + high dose methotrexate, leucovorin, vincristine, procarbazine, dexamethasone, and cytarabine.
Patients with meningeal involvement will receive additional methotrexate and leucovorin.
|
Rituximab is administered intravenously.
The initial rate is 50 mg/hr for the first hour.
If no toxicity is seen, the rate may be escalated gradually in 50 mg/hour increments at 30-minute intervals to a maximum of 300 mg/hr.
If the first dose is well tolerated, the initial rate for subsequent dose is 100 mg/hr, increased gradually in 100 mg/hr increments at 30-minute intervals, not to exceed 400 mg/hr.
Other Names:
3 g/m2/day in 500 cc D5W IV over 2 hrs.
x 2 doses 24hrs.
apart, Weeks 11, 14
Other Names:
16mg (week 1) PO daily Weeks 1, 2, 3, 4, 5, 6 Taper by 4 mg/wk, weeks 2, 3, by 2 mg/wk week 4, 5, 6
Other Names:
25 mg PO/IV every 6 hrs.
x 12 doses, Weeks 1, 3, 5, 7, 9 For patients with meningeal involvement additionally 10 mg PO every 12 hrs.
x 8 doses, Weeks 2, 4, 6, 8, 10
Other Names:
3.5 g/m2In 500 cc D5W + 25 mEq NaHCO3 IV over 2 hours, Weeks 1, 3, 5, 7, 9 For patients with meningeal involvement additionally: 12 mg Intrathecally, in preservative-free sterile .9NS Weeks 2, 4, 6, 8, 10 Via Ommaya or lumbar puncture
Other Names:
100 mg/m2 PO daily x 7 days Weeks 1, 5, 9
Other Names:
1.4 mg/m2 IV push, Weeks 1, 3, 5, 7, 9 2m2 (2.8 mg) dose cap
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete Response Rate - Locally Reviewed
Time Frame: For the primary endpoint, complete response will be based on disease status at three weeks post the end of therapy (week 17).
|
Assessed by the ECOG-ACRIN data manager based upon local review of images and data sent by the local sites. Treatment response was determined by calculating the sum of the maximal cross section in 2 separate axes using enhancing lesion(s) on CT or MRI imaging. The same imaging modality was to be used throughout assessment. Complete response was defined as the disappearance of all contrast enhancing tumor size on CT or MRI, patient was off all glucocorticoids, and resolution of all meningeal and vitreous involvement if present. Response must have lasted at least 4 weeks. |
For the primary endpoint, complete response will be based on disease status at three weeks post the end of therapy (week 17).
|
Collaborators and Investigators
Investigators
- Study Chair: Lode J. Swinnen, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Study Chair: Deborah T. Blumenthal, MD, University of Utah
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protease Inhibitors
- Protective Agents
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Dermatologic Agents
- Micronutrients
- Vitamins
- Reproductive Control Agents
- Antidotes
- Vitamin B Complex
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Dexamethasone
- Dexamethasone acetate
- BB 1101
- Rituximab
- Leucovorin
- Levoleucovorin
- Cytarabine
- Methotrexate
- Vincristine
- Dexamethasone 21-phosphate
- Procarbazine
Other Study ID Numbers
- CDR0000475776
- ECOG-E1F05 (Other Identifier: ECOG-ACRIN)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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