Leukemia, Lymphoma
Conditions
Keywords
untreated adult acute lymphoblastic leukemia, L3 adult acute lymphoblastic leukemia, contiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult Burkitt lymphoma, stage I adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma
Brief summary
RATIONALE: Drugs used in chemotherapy, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. 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. Giving combination chemotherapy together with rituximab may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with rituximab works in treating patients with newly diagnosed Burkitt's lymphoma or leukemia.
Detailed description
OBJECTIVES: Primary * Determine the overall response rate, 1-year event-free survival, and overall survival of adult patients with newly diagnosed Burkitt or atypical Burkitt lymphoma or leukemia treated with dose-intensified induction therapy comprising cyclophosphamide, vincristine, prednisone, and rituximab followed by consolidation therapy comprising rituximab and high-dose cyclophosphamide. * Determine the grade 3 or higher non-hematologic toxic effects and overall tolerability of this regimen in these patients. Secondary * Determine the 3-year event-free survival and overall survival of patients treated with this regimen. * Determine the general patterns of CNS and systemic relapse in patients treated with this regimen. OUTLINE: This is a multicenter study. * Dose-intensified CVP induction therapy: Patients receive cyclophosphamide IV and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5 and rituximab IV on days 1 and 8, and high-dose methotrexate IV with leucovorin calcium IV rescue on day 8. Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 3 and continuing until blood counts recover. Treatment repeats approximately every 14 days for 2 courses. * CNS therapy: Patients receive cytarabine intrathecally (IT) with or without hydrocortisone IT on days 1, 4, and 11 of each induction therapy course. Patients with evidence of CNS involvement by lymphoma continue to receive cytarabine IT twice weekly during any induction therapy treatment delay. Patients who demonstrate CSF clearance receive cytarabine IT once weekly for 4 doses and then once every other week for 4 doses during consolidation therapy. Patients with disease progression during induction therapy or persistent CNS involvement by lymphoma are removed from the study. All other patients proceed to consolidation therapy. * Consolidation therapy: Patients receive rituximab IV on day -4 and high-dose cyclophosphamide IV on days -3, -2, -1, and 0. Patients receive G-CSF SC once daily beginning on day 6 and continuing until blood counts recover OR pegfilgrastim SC once on day 6. Patients then receive rituximab IV once weekly for 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 3 years. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.
Interventions
BIOLOGICALFilgrastim
5 mcg/kg/day starting on Day 3 after each R-CVP cycle and on Day 6 after HiCy.
BIOLOGICALRituximab
375 mg/m\^2 on Day 1 and Day 8 of each R-CVP cycle. 375 mg/m\^2 on Day -4 of HiCy and weekly for four weeks after HiCy.
DRUGCyclophosphamide
1500 mg/m\^2 on Day 1 of each R-CVP cycle. 50 mg/kg/day on Days -3, -2, -1, and 0 of HiCy.
DRUGCytarabine
100 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.
DRUGMethotrexate
3 g/m\^2 on Day 8 of each cycle of R-CVP.
DRUGPrednisone
100 mg on Days 1-5 of each cycle of R-CVP.
DRUGHydrocortisone
50 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.
DRUGVincristine
1.4 mg/m\^2 on Day 1 of each cycle of R-CVP.
DRUGLeucovorin
25 mg four times daily after methotrexate administration. Dosing continues until adequate methotrexate levels are reached.
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
30 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed diagnosis of 1 of the following: * Classic, sporadic Burkitt's lymphoma * Burkitt's leukemia (FAB L3 acute lymphoblastic leukemia) * Atypical Burkitt/Burkitt's-like lymphoma or leukemia, defined by the following criteria: * Characteristic morphologic features * High proliferative index AND Ki-67 ≥ 85% * Any stage allowed * Newly diagnosed or untreated disease * Steroids allowed PATIENT CHARACTERISTICS: Age * 30 and over Performance status * Not specified Life expectancy * Not specified Renal * No known irreversible renal dysfunction that would preclude treatment with high-dose cyclophosphamide Cardiovascular * No known significant cardiac dysfunction that would preclude treatment with high-dose cyclophosphamide Other * Not pregnant or nursing * No known HIV positivity * No other malignancy within the past 3 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior chemotherapy for lymphoma * A maximum of 2 prior doses of intrathecal chemotherapy are allowed Endocrine therapy * Not specified Radiotherapy * No prior radiation therapy for lymphoma Surgery * Prior complete or incomplete surgical resection of lymphoma allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Up to 3 months | Number of participants who have a complete or partial remission (2007 International Working Group criteria). |
| Overall Survival | 1 year and 3 years | Percentage of participants alive at 1 year and at 3 years. |
| Event-free Survival | 1 year and 3 years | Percentage of participants alive without relapse at 1 year and 3 years. |
| Percentage of Participants Experiencing Grade 3-5 Toxicity | Up to 2 years | Percentage of participants experiencing at least one grade 3-5 adverse event (by CTCAE 3.0 criteria). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse Pattern | Up to 6 months | Percentage of participants experiencing central nervous system (CNS) and systemic relapse. |
Countries
United States
Participant flow
Pre-assignment details
2 participants were found to be HIV+ after initiating the study and are considered to be screen failures as defined by the protocol.
Participants by arm
| Arm | Count |
|---|---|
| R-CVP + HiCy Protocol intervention consists of two fifteen-day cycles of cyclophosphamide (Cy), vincristine (V), prednisone (P), rituximab (R), with filgrastim support. CNS intervention consists of three days of cytarabine and hydrocortisone and one day of methotrexate (with leucovorin support) for each cycle. After those two cycles, rituximab and high-dose cyclophosphamide (HiCy) will be given. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 4 |
Baseline characteristics
| Characteristic | R-CVP + HiCy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 53 years |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 21 |
| other Total, other adverse events | 21 / 21 |
| serious Total, serious adverse events | 12 / 21 |
Outcome results
Primary
Event-free Survival
Percentage of participants alive without relapse at 1 year and 3 years.
Time frame: 1 year and 3 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| R-CVP + HiCy | Event-free Survival | 1 year | 52 percentage of participants |
| R-CVP + HiCy | Event-free Survival | 3 years | 52 percentage of participants |
Primary
Overall Response Rate
Number of participants who have a complete or partial remission (2007 International Working Group criteria).
Time frame: Up to 3 months
Population: The 4 participants who died during treatment were not analyzed for this outcome.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| R-CVP + HiCy | Overall Response Rate | Complete remission | 11 Participants |
| R-CVP + HiCy | Overall Response Rate | Partial remission | 2 Participants |
Primary
Overall Survival
Percentage of participants alive at 1 year and at 3 years.
Time frame: 1 year and 3 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| R-CVP + HiCy | Overall Survival | 1 year | 57 percentage of participants |
| R-CVP + HiCy | Overall Survival | 3 years | 57 percentage of participants |
Primary
Percentage of Participants Experiencing Grade 3-5 Toxicity
Percentage of participants experiencing at least one grade 3-5 adverse event (by CTCAE 3.0 criteria).
Time frame: Up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| R-CVP + HiCy | Percentage of Participants Experiencing Grade 3-5 Toxicity | 21 Participants |
Secondary
Relapse Pattern
Percentage of participants experiencing central nervous system (CNS) and systemic relapse.
Time frame: Up to 6 months
Population: The 4 participants who died during treatment were not analyzed for this outcome.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| R-CVP + HiCy | Relapse Pattern | Systemic relapse only | 3 Participants |
| R-CVP + HiCy | Relapse Pattern | Systemic and CNS relapse | 2 Participants |