Clinical trial NCT00248534: Rituximab, Temozolomide, and Methylprednisolone in Treating Patients With Recurrent Primary CNS Non-Hodgkin's Lymphoma
Official title: A Phase II Study of Rituximab and Temozolomide in Recurrent Primary CNS Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lymphoma
Keywords: primary central nervous system non-Hodgkin lymphoma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-11-04
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Objective Response
timeFrame: 2 months
Secondary outcomes:
measure: Number of Participants Alive at 3 Years
timeFrame: 3 years
measure: 1 Year Overall Survival Rate
timeFrame: 1 year
measure: 6-month Progression-free Survival
timeFrame: 6 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Pittsburgh
country: United States
facility: Hillman Cancer Center at University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Lauren E. Abrey, MD
role: STUDY_CHAIR
References:
citation: Nayak L, Abrey LE, Drappatz J, et al.: Multicenter phase II trial of temozolomide (TMZ) and rituximab (RIT) for recurrent primary CNS lymphoma (PCNSL): North American Brain Tumor Consortium (NABTC) study 05-01. [Abstract] J Clin Oncol 29 (Suppl 15): A-2039, 2011.
citation: Nayak L, Abrey LE, Drappatz J, Gilbert MR, Reardon DA, Wen PY, Prados M, Deangelis LM, Omuro A; North American Brain Tumor Consortium. Multicenter phase II study of rituximab and temozolomide in recurrent primary central nervous system lymphoma. Leuk Lymphoma. 2013 Jan;54(1):58-61. doi: 10.3109/10428194.2012.698736. Epub 2012 Jul 9.