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

Johns Hopkins Medicine

Status and phase: Terminated; Phase 2

Conditions: Lymphoma

Treatments: Biological: rituximab; Drug: methylprednisolone; Drug: temozolomide

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00248534

CDR0000445289 (Registry Identifier)

U01CA062399 (U.S. NIH Grant/Contract)

NABTC05-01

NABTC-05-01

NCI-2012-02673 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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16 participants in 1 patient group

IV Rituximab

Experimental group

Description:

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

Treatment:

Drug: temozolomide

Drug: methylprednisolone

Biological: rituximab