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

NCT ID: NCT00248534

Last Updated: 2018-09-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2012-09-30

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.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

given IV days 1,8, 15 and 22

methylprednisolone

Intervention Type: DRUG

2hr IV every 28 days post consolidation cycles of Temozolomide (TMZ) (6 cycles TMZ = Consolidation cycles)

temozolomide

Intervention Type: DRUG

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

Interventions

rituximab

given IV days 1,8, 15 and 22

Intervention Type: BIOLOGICAL

methylprednisolone

2hr IV every 28 days post consolidation cycles of Temozolomide (TMZ) (6 cycles TMZ = Consolidation cycles)

Intervention Type: DRUG

temozolomide

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

Intervention Type: DRUG

Other Intervention Names

TMZ

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lauren E. Abrey, MD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Locations

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 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

Hillman Cancer Center at University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: RESULT

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.

Reference Type: DERIVED

PMID: 22656234 (View on PubMed)

Other Identifiers

NABTC-05-01

Identifier Type: -

Identifier Source: secondary_id

CDR0000445289

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02673

Identifier Type: REGISTRY

Identifier Source: secondary_id

U01CA062399

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NABTC05-01

Identifier Type: -

Identifier Source: org_study_id