Rituximab, Temozolomide, and Methylprednisolone in Treating Patients With Recurrent Primary CNS Non-Hodgkin's Lymphoma

August 28, 2018 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

A Phase II Study of Rituximab and Temozolomide in Recurrent Primary CNS Lymphoma

RATIONALE: 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. Drugs used in chemotherapy, such as temozolomide and methylprednisolone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Rituximab may help chemotherapy kill more cancer cells by making cancer cells more sensitive to the drugs. Giving rituximab together with temozolomide and methylprednisolone may be an effective treatment for primary CNS non-Hodgkin's lymphoma.

PURPOSE: This phase II trial is studying how well giving rituximab together with temozolomide and methylprednisolone works in treating patients with recurrent primary CNS non-Hodgkin's lymphoma.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the response rate in patients with recurrent primary CNS non-Hodgkin's lymphoma treated with rituximab, temozolomide, and methylprednisolone.

Secondary

  • Determine the overall and 6-month progression-free survival of patients treated with this regimen.

OUTLINE: Induction therapy: Patients receive rituximab IV over 30-60 minutes on days 1, 8, 15, and 22 and oral temozolomide daily on days 1-7 and 15-21. After day 28, patients with stable disease or better proceed to consolidation therapy.

Consolidation therapy: Patients receive oral temozolomide daily on days 1-5. Treatment repeats every 28 days for up to 6 courses. Patients achieving a complete remission proceed to maintenance therapy.

Maintenance therapy: Patients receive methylprednisolone IV over 2 hours on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within approximately 13.3 months.

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • UCSF Helen Diller Family Comprehensive Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Hillman Cancer Center at University of Pittsburgh Cancer Institute
    • Texas
      • Houston, Texas, United States, 77030-4009
        • M. D. Anderson Cancer Center at University of Texas
      • San Antonio, Texas, United States, 78284-6220
        • University of Texas Health Science Center at San Antonio
    • Wisconsin
      • Madison, Wisconsin, United States, 53792-6164
        • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed primary CNS non-Hodgkin's lymphoma by brain biopsy, positive cerebrospinal fluid cytology, or vitrectomy

    • Recurrent disease

  • Measurable disease, define as bi-dimensionally measurable lesions with clearly defined margins by brain MRI or CT scan

    • Radiographical evidence of tumor progression by MRI or CT scan
    • Steroid therapy must be stable for 5 days prior to scan

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Karnofsky 60-100%

Life expectancy

  • More than 8 weeks

Hematopoietic

  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL (transfusion allowed)

Hepatic

  • SGOT < 2 times upper limit of normal (ULN)
  • Bilirubin < 2 times ULN
  • No active or latent hepatitis B infection

Renal

  • Creatinine < 1.5 mg/dL OR
  • Creatinine clearance ≥ 60 mL/min

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No uncontrolled significant medical illness that would preclude study treatment
  • No active infection
  • No active HIV infection
  • No concurrent disease that would dangerously alter drug metabolism or obscure toxicity

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • At least 7 days since prior interferon or thalidomide
  • No concurrent prophylactic filgrastim (G-CSF)
  • No concurrent immunotherapy

Chemotherapy

  • No prior temozolomide
  • At least 14 days since prior methotrexate
  • At least 21 days since prior procarbazine
  • At least 42 days since prior nitrosoureas
  • No other concurrent chemotherapy

Endocrine therapy

  • See Disease Characteristics
  • At least 7 days since prior tamoxifen
  • No concurrent hormonal therapy

Radiotherapy

  • No concurrent radiotherapy

Surgery

  • Not specified

Other

  • Recovered from all prior therapy
  • At least 28 days since prior investigational agents
  • At least 28 days since other prior cytotoxic therapy
  • At least 7 days since other prior non-cytotoxic agents (e.g., tretinoin) (radiosenitizers allowed)
  • No other concurrent investigational drugs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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: IV Rituximab

IV Rituximab 750mg/m2 single infusion every week for up to 4 weeks.

Induction: Rituximab (750mg/m2) Day 1, 8, 15 and 22 and Temozolomide [TMZ] (150mg/m2) days 1-7 and 15-21, followed by six cycles of consolidation TMZ 150-200mg/m2 x5/28days, followed by maintenance with methylprednisolone (1g IV every 28days) until progression
Biological: rituximab
given IV days 1,8, 15 and 22
Drug: methylprednisolone
2hr IV every 28 days post consolidation cycles of Temozolomide (TMZ) (6 cycles TMZ = Consolidation cycles)
Drug: temozolomide
Induction Days 1-7 and 15-21 (150mg/m2 PO) Consolidation days 1-5 every 28 days X 6 cycles
Other Names:
  • TMZ

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Objective Response
Time Frame: 2 months
Objective response rate of the combination of Rituximab and TMZ
2 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Alive at 3 Years
Time Frame: 3 years
The intent was to measure Median Overall Survival at 3 years, however only one participant was analyzable at this time point. Therefore, the number of participants who survived is reported instead.
3 years
1 Year Overall Survival Rate
Time Frame: 1 year
1 year
6-month Progression-free Survival
Time Frame: 6 months

Scan at 6 months

Complete response: Complete disappearance of all tumor on MRI scan, off all glucocorticoids with stable or improving neurological exam minimum of 4 wks

Partial response: Greater than or equal 50% reduction in tumor size on MRI, on sable or decreasing glucocorticoids with stable or improving neurological exam for a minimum of 4 wks.

Progressive disease: Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion.

Stable disease: Clinical status and MRI does not qualify for complete response, partial response or progression
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

September 1, 2012

Study Completion (Actual)

September 1, 2012

Study Registration Dates

First Submitted

November 3, 2005

First Submitted That Met QC Criteria

November 3, 2005

First Posted (Estimate)

November 4, 2005

Study Record Updates

Last Update Posted (Actual)

September 4, 2018

Last Update Submitted That Met QC Criteria

August 28, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NABTC05-01
  • U01CA062399 (U.S. NIH Grant/Contract)
  • NABTC-05-01
  • CDR0000445289 (Registry Identifier: PDQ (Physician Data Query))
  • NCI-2012-02673 (Registry Identifier: CTRP (Clinical Trials Reporting System))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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