We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu
IMPORTANT: Due to the lapse in government funding, the information on this web site may not be up to date, transactions submitted via the web site may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted. Updates regarding government operating status and resumption of normal operations can be found at opm.gov.

Rituximab and Combination Chemotherapy in Treating Patients With Primary Central Nervous System Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00335140
Recruitment Status : Terminated (slow accrual)
First Posted : June 8, 2006
Results First Posted : June 28, 2017
Last Update Posted : June 28, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Lymphoma Biological: Rituximab Drug: Cytarabine Drug: Dexamethasone Drug: Leucovorin Drug: Methotrexate Drug: Procarbazine Drug: Vincristine Phase 2

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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Rituximab Given in Conjunction With Standard Chemotherapy in Primary Central Nervous System (CNS) Lymphoma
Study Start Date : December 2006
Primary Completion Date : July 2015
Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Rituximab
U.S. FDA Resources

Arms and Interventions

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.
Biological: Rituximab
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 Name: Rituxan
Drug: Cytarabine
3 g/m2/day in 500 cc D5W IV over 2 hrs. x 2 doses 24hrs. apart, Weeks 11, 14
Other Names:
  • Cytosar-U
  • Ara-C
  • Arabinosylcytosine
Drug: Dexamethasone
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:
  • Decadron
  • Dexasone
  • Diodex
  • Hexadrol
  • Maxidex
  • dexamethasone sodium phosphate
  • dexamethasone acetate
Drug: Leucovorin
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 Name: leucovorin calcium
Drug: Methotrexate

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:
  • Otrexup
  • Rasuvo
  • Rheumatrex
  • Trexall
  • Amethopterin
  • Methotrexate Sodium
  • MTX
Drug: Procarbazine
100 mg/m2 PO daily x 7 days Weeks 1, 5, 9
Other Names:
  • Matulane
  • Procarbazine hydrochloride
Drug: Vincristine
1.4 mg/m2 IV push, Weeks 1, 3, 5, 7, 9 2m2 (2.8 mg) dose cap
Other Names:
  • Vincristine Sulfate
  • Oncovin
  • Vincasar
  • LCR
  • VCR


Outcome Measures

Primary Outcome Measures :
  1. 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.



Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00335140


  Show 68 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Lode J. Swinnen, MD Sidney Kimmel Comprehensive Cancer Center
Study Chair: Deborah T. Blumenthal, MD University of Utah
More Information

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00335140     History of Changes
Other Study ID Numbers: CDR0000475776
ECOG-E1F05 ( Other Identifier: ECOG-ACRIN )
First Posted: June 8, 2006    Key Record Dates
Results First Posted: June 28, 2017
Last Update Posted: June 28, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eastern Cooperative Oncology Group:
primary central nervous system non-Hodgkin lymphoma

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Rituximab
Methotrexate
Cytarabine
Vincristine
Procarbazine
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action