Leukemia, Lymphoma
Conditions
Keywords
untreated adult acute lymphoblastic leukemia, L3 adult acute lymphoblastic leukemia, stage I adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, contiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult Burkitt lymphoma
Brief summary
RATIONALE: Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the numbers of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. Combining chemotherapy with rituximab and filgrastim may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining rituximab with chemotherapy and filgrastim in treating patients who have Burkitt's lymphoma or Burkitt's leukemia.
Detailed description
OBJECTIVES: * Determine the complete response rate in patients with previously untreated Burkitt's lymphoma or Burkitt's leukemia treated with rituximab and high-intensity chemotherapy with filgrastim (G-CSF) support. * Determine the progression-free and overall survival of patients treated with this regimen. * Determine the feasibility and toxicity of this regimen in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to disease (leukemia vs lymphoma). * Course 1: Patients receive cyclophosphamide IV over 5-15 minutes daily on days 1-5 and oral prednisone on days 1-7. Allopurinol PO will be given on days 1-14. * Courses 2, 4, and 6: Patients receive ifosfamide IV over 1 hour daily on days 1-5; vincristine IV over 10 minutes and methotrexate IV over 24 hours on day 1; leucovorin calcium IV over 15 minutes every 6 hours on day 2; cytarabine IV over 2 hours on days 4 and 5 and etoposide IV over 1 hour daily on days 4 and 5; oral dexamethasone daily on days 1-5; and methotrexate and cytarabine intrathecally (IT) on day 1. During course 2, patients receive rituximab IV over 1-4 hours on days 8, 10, and 12. During courses 4 and 6, patients receive rituximab IV over 1 hour on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 7 and continuing until blood counts recover. * Courses 3, 5, and 7: Patients receive cyclophosphamide IV over 5-15 minutes daily on days 1-5; vincristine IV over 10 minutes and methotrexate IV over 24 hours on day 1; leucovorin calcium IV every 6 hours on day 2; doxorubicin IV daily on days 4 and 5; oral dexamethasone daily on days 1-5; methotrexate and cytarabine IT on day 1; and rituximab IV over 1 hour on day 8. Patients also receive G-CSF as in courses 2, 4, and 6. After course 3, treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years. PROJECTED ACCRUAL: A total of 100 patients (50 per stratum) will be accrued for this study within 3 years.
Interventions
DRUGprednisone
60 mg/sq m PO/day Days 1-7 course I
DRUGvincristine sulfate
2 mg IV push Day 1 courses II-VII
DRUGAllopurinol
300 mg/day PO Days 1-14, course I
BIOLOGICALfilgrastim
5 ug/kg/day sub Q injection day 7 until ANC\>5000/ul courses II-VII
BIOLOGICALrituximab
Day 8 course II 50 mg/sq m IV infusion: d 8 course IV & VI 375mg/sq m IV Day 10 course II: 325 mg/sq m IV infusion Day 12 course II: 375 mg/sq m IV infusion
DRUGcyclophosphamide
200 mg/sq m/day IV infusion over 5-15 min days 1-5, courses I, III, V, VII
DRUGcytarabine
1 g/sq m/day IV infusion Days 4 & 5, courses II, IV, VI
DRUGdexamethasone
10mg/sq m PO or IV Days 1-5 courses II-VII
DRUGdoxorubicin hydrochloride
25 mg/sq m/day IV infusion Days 4 & 5 courses III,V, VII
DRUGetoposide
80 mg/sq m/day IV infusion Days 4 & 5 courses II, IV, VI
DRUGifosfamide
800 mg/sq m/day IV infusion Days 1-5 courses II, IV, VI
DRUGleucovorin calcium
25mg/sq m IV infusion over 15 min then 10 mg IV q 6 hrs until serum MTX \<10nM, courses II-VII
DRUGmethotrexate
1.5 g/sq m IV infusion Day 1 courses II-VII
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically, cytogenetically, or immunophenotypically confirmed Burkitt's leukemia or Burkitt's or Burkitt-like lymphoma * L3 morphology surface IgG expression * Cytogenetic evidence for t(8;14), t(8;22), or t(2;8) * Previously untreated disease except hydroxyurea for leukocytosis * CNS involvement allowed * Patients with Burkitt's leukemia or Burkitt's lymphoma with bone marrow involvement must also be enrolled on CALGB-8461 * Patients with Burkitt's leukemia must also be enrolled on CALGB-9665 PATIENT CHARACTERISTICS: Age: * 16 and over Hepatic: * Bilirubin no greater than 1.5 times upper limit of normal (ULN) Renal: * Creatinine no greater than 1.5 times ULN Other: * HIV negative * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: * No concurrent interleukin-11 Chemotherapy: * See Disease Characteristics * No other concurrent chemotherapy Endocrine therapy: * No concurrent hormonal therapy except for non-disease-related conditions (e.g., insulin for diabetes) * No concurrent steroids except for adrenal failure Radiotherapy: * No concurrent palliative radiotherapy except whole-brain irradiation for documented CNS disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate | 6 months | Response is assessed by investigator according to Revised Response Criteria for Malignant Lymphoma. Complete response requires disappearance of all evidence of disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2 Year Event Free Survival | 2 years | Percentage of patients who were event free at 2 years. The 2-year event free rate was estimated using the Kaplan Meier method. An event is defined as death, progression or treatment failure. |
| 2 Year Overall Survival | 2 years | Percentage of participants who were alive at 2 years. The 2 year survival, with 95% confidence interval, was estimated using the Kaplan Meier method. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab With High Intensity Chemotherapy Cycle1: Cyclophosphamide 100 mg/m\^2/day (d) IV (d 1-5), Prednisone 60 mg/m\^2/d oral (d 1-7), Allopurinal 300 mg/d oral (d 1-14)
Cycle 2, 4 & 6 (21 day): Ifosfamide 800 mg/m\^2/d (d 1-5), Dexamethasone 10 mg/m\^2/d (d1-5), Methotrexate 150 mg/m\^2 load, then 1.35 g/m\^2 over 23.5 h (d 1), Leucovorin 25 mg/m\^2 36 h after methotrexate (d 2) then 10 mg/m\^2 every 6 h, Vincristine 2 mg push (d 1), Cytarabine 1000 mg/m\^2/d over 2 h (d 4-5), Etoposide 80 mg/m\^2.d over 1 h (d 4-5), Filgrastim 5 mg/kg/d (d 7-21 as needed), Rituximab 50 mg/m\^2 d 8 cycle 2 only, 375 mg/m\^2/d (d 10, 12 cycle 2, d 8 cycle 4 & 6)
Cycle 3, 5 & 7 (21 day): Cyclophosphamide 200 mg/m\^2/day (d) IV (d 1-5), Dexamethasone 10 mg/m\^2/d (d1-5), Methotrexate 150 mg/m\^2 load, then 1.35 g/m\^2 over 23.5 h (d 1), Leucovorin 50 mg/m\^2 36 h after methotrexate (d 2) then 10 mg/m\^2 every 6 h, Vincristine 2 mg push (d 1), Doxorubicin 25 mg/m\^2/d (d 4-5), Filgrastim 5 mg/kg/d (d 7-21 as needed), Rituximab 375 mg/m\^2/d (d 8) | 105 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 11 |
| Overall Study | Death | 9 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Progression | 2 |
| Overall Study | Subsequent treatment | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Rituximab With High Intensity Chemotherapy |
|---|---|
| Age, Continuous | 43 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 98 Participants |
| Region of Enrollment United States | 105 participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 101 / 105 |
| serious Total, serious adverse events | 61 / 105 |
Outcome results
Primary
Complete Response Rate
Response is assessed by investigator according to Revised Response Criteria for Malignant Lymphoma. Complete response requires disappearance of all evidence of disease.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab With High Intensity Chemotherapy | Complete Response Rate | 83 percentage of participants |
Secondary
2 Year Event Free Survival
Percentage of patients who were event free at 2 years. The 2-year event free rate was estimated using the Kaplan Meier method. An event is defined as death, progression or treatment failure.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab With High Intensity Chemotherapy | 2 Year Event Free Survival | 78 percentage of participants |
Secondary
2 Year Overall Survival
Percentage of participants who were alive at 2 years. The 2 year survival, with 95% confidence interval, was estimated using the Kaplan Meier method.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab With High Intensity Chemotherapy | 2 Year Overall Survival | 80 percentage of participants |