Lymphoma
Conditions
Keywords
primary central nervous system non-Hodgkin lymphoma
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.
Interventions
BIOLOGICALrituximab
given IV days 1,8, 15 and 22
DRUGmethylprednisolone
2hr IV every 28 days post consolidation cycles of Temozolomide (TMZ) (6 cycles TMZ = Consolidation cycles)
DRUGtemozolomide
Induction Days 1-7 and 15-21 (150mg/m2 PO) Consolidation days 1-5 every 28 days X 6 cycles
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response | 2 months | Objective response rate of the combination of Rituximab and TMZ |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Alive at 3 Years | 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. |
| 1 Year Overall Survival Rate | 1 year | — |
| 6-month Progression-free Survival | 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 |
Countries
United States
Participant flow
Recruitment details
patients enrolled from 2005 through 2008. Patients enrolled in an outpatient multi-institutional clinics
Participants by arm
| Arm | Count |
|---|---|
| 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
rituximab: given IV days 1,8, 15 and 22
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 | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | IV Rituximab |
|---|---|
| Age, Customized | 63 years |
| Karnofsky Performance Status Scale | 90 units on a scale |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Percentage of Participants With Objective Response
Objective response rate of the combination of Rituximab and TMZ
Time frame: 2 months
Population: 2 patients were not evaluable, one died prematurely and the other withdrew consent before the first scan (during induction cycle)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV Rituximab | Percentage of Participants With Objective Response | 14 percent of participants |
Secondary
1 Year Overall Survival Rate
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV Rituximab | 1 Year Overall Survival Rate | 71 percentage of participants |
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
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV Rituximab | 6-month Progression-free Survival | 13 percentage of participants |
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.
Time frame: 3 years
Population: One patient died prematurely, one patient withdrew consent before first scan (during induction), 13 patients came off study due to progression of disease.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Rituximab | Number of Participants Alive at 3 Years | 1 Participants |