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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00248534
• Other study ID #: NABTC05-01
• Secondary ID: NABTC-05-01CDR00
• Status: Terminated
• Phase: Phase 2
• Start date: September 2005
• Est. completion date: September 2012

Study information

• Verified date: August 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma

Intervention

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)
• temozolomide
Induction Days 1-7 and 15-21 (150mg/m2 PO) Consolidation days 1-5 every 28 days X 6 cycles

Locations

Country	Name	City	State
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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-203

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Objective Response	Objective response rate of the combination of Rituximab and TMZ	2 months
Secondary	Number of Participants Alive at 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
Secondary	1 Year Overall Survival Rate		1 year
Secondary	6-month Progression-free Survival	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