|Phase II||Biomarker/Laboratory analysis, Treatment||Closed||2 to 31||NCI, Other||CDR0000396777|
COG-ADVL04P2, ADVL04P2, NCT00098839
RATIONALE: Monoclonal antibodies, such as epratuzumab, 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 work in different ways to stop the growth of cancer cells, either by killing them or by stopping them from dividing. Giving monoclonal antibody therapy together with combination chemotherapy may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving epratuzumab together with combination chemotherapy works in treating young patients with relapsed acute lymphoblastic leukemia.
Further Study Information
- Determine the feasibility of epratuzumab administered alone and in combination with re-induction combination chemotherapy in pediatric patients with relapsed CD22-positive acute lymphoblastic leukemia.
- Determine the toxic effects of this regimen in these patients.
- Determine the antitumor activity of this regimen in these patients.
- Determine the pharmacokinetics of epratuzumab in these patients.
- Determine the biologic activity of epratuzumab using measurements of minimal residual disease in these patients.
- Determine the human anti-human antibody (HAHA) response in patients treated with this regimen.
OUTLINE: This is a multicenter study comprising a feasibility part A (closed to accrual as of 10/30/06) followed by a pilot part B study. Patients enrolled in part B are stratified according to relapse (first early marrow relapse occurring < 36 months from initial diagnosis vs first late marrow relapse occurring ≥ 36 months from initial diagnosis vs in second or subsequent relapse).
- Part A (closed to accrual as of 10/30/06):
- Reduction therapy: Patients receive epratuzumab IV over 1 hour on days -14, -10, -6, and -2 and cytarabine intrathecally (IT) on day -14*.
NOTE: *Patients who receive IT chemotherapy within 7 days of study entry as prior maintenance chemotherapy (e.g., before the diagnosis of relapse) will not receive this first dose of IT cytarabine.
- Re-induction therapy (block 1): Patients receive vincristine IV on days 1, 8, 15, and 22; oral prednisone two or three times daily on days 1-29; pegaspargase intramuscularly (IM) on days 2, 9, 16, and 23; dexrazoxane IV followed by doxorubicin IV over 15 minutes on day 1; methotrexate IT on days 15 and 29 for CNS-negative disease; and epratuzumab IV over 1 hour on days 8, 15, 22, and 29. Patients with CNS-positive disease also receive triple IT therapy (ITT) consisting of methotrexate, cytarabine, hydrocortisone on days -10, -6, 1 and 15.
- Re-induction therapy (block 2): Beginning at least 7 days after the last dose of IT chemotherapy, patients receive etoposide IV over 2 hours and cyclophosphamide IV over 30 minutes on days 1-5. Patients also receive high-dose methotrexate IV continuously over 24 hours on day 22. Beginning 42 hours after the start of the methotrexate infusion (day 24), patients receive leucovorin calcium IV every 6 hours for a minimum of 3 doses. Patients with CNS-negative disease also receive methotrexate IT on days 1 and 22. Patients with CNS-positive disease will receive triple IT as in re-induction therapy (block 1) on days 1 and 22. Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 6 and continuing until blood counts recover.
- Re-induction therapy (part 3): Beginning at least 7 days after the last dose of IT chemotherapy, patients receive cytarabine IV over 3 hours twice daily on days 1, 2, 8, and 9 and asparaginase IM on days 2 and 9. Patients receive G-CSF SC once daily beginning on day 10 and continuing until blood counts recover.
- Part B:
- Re-induction therapy (block 1): Patients receive vincristine, prednisone, pegaspargase, doxorubicin, cytarabine, methotrexate, and epratuzumab as in phase I re-induction therapy (block 1). Patients with CNS-negative disease receive methotrexate IT on days 1 and 22. Patients with CNS-positive disease receive triple IT therapy comprising methotrexate, cytarabine, and hydrocortisone on days 8, 15, 22, and 29.
- Re-induction therapy (blocks 2 and 3): Patients receive re-induction therapy blocks 2 and 3 as in the part A re-induction therapy (blocks 2 and 3) portion of the study.
Patients are followed annually.
PROJECTED ACCRUAL: A total of 116 patients will be accrued for this study.
- Diagnosis of B-cell precursor acute lymphoblastic leukemia (ALL)
- At least 25% expression of CD22 by immunophenotyping
- In marrow relapse (M3 bone marrow) with or without associated extramedullary disease as defined by 1 of the following:
- In first or later marrow relapse occurring any time after initial diagnosis (part A [closed to accrual as of 10/30/06] or B)
- In first, early marrow relapse with or without associated extramedullary disease occurring < 36 months from the time of initial diagnosis (part B only)
- No B-cell L3 morphology OR evidence of MYC translocation by molecular or cytogenetic analysis
- No Down syndrome
- Patients with CNS or other extramedullary site involvement are allowed
- 2 to 31 years old
- Karnofsky 50-100% (for patients > 10 years of age)
- Lansky 50-100% (for patients ≤ 10 years of age)
- Not specified
- WBC ≤ 50,000/mm^3 (part A only [closed to accrual as of 10/30/06])
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- ALT ≤ 5 times ULN ( unless disease-related)
- Albumin ≥ 2 g/dL
- Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min OR
- Creatinine as defined by age as follows:
- ≤ 0.5 mg/dL (for patients < 1 year old)
- ≤ 0.8 mg/dL (for patients 1 to 5 years old)
- ≤ 1.0 mg/dL (for patients 6 to 10 years old)
- ≤ 1.2 mg/dL (for patients 11 to 15 years old)
- ≤ 1.5 mg/dL (for patients > 15 years old)
- Shortening fraction ≥ 27% by echocardiogram OR
- Ejection fraction ≥ 45% by MUGA
- No dyspnea at rest
- No exercise intolerance
- Pulse oximetry > 94%
- No active or uncontrolled infection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- Recovered from prior immunotherapy
- At least 4 months since prior stem cell transplantation or rescue AND no evidence of active graft-vs-host disease
- At least 7 days since prior hematopoietic growth factors
- At least 7 days since prior biologic therapy*
- No other concurrent immunotherapy
- No other concurrent biologic therapy NOTE: *A longer washout period may be required for agents with known adverse events that occur beyond 7 days after administration
- Recovered from prior chemotherapy
- No waiting period for children who relapse while receiving standard ALL maintenance therapy
- No prior cumulative anthracycline exposure > 400 mg/m^2*
- No concurrent chemotherapy NOTE: *Each 10 mg/m2 of idarubicin should be calculated as the isotoxic equivalent of 30 mg/m2 of daunorubicin or doxorubicin
- Not specified
- Recovered from prior radiotherapy
- No concurrent radiotherapy
- Not specified
- At least 2 days since prior hydroxyurea
- No other concurrent investigational drugs
- No other concurrent anticancer agents
Trial Lead Organizations/Sponsors
Children's Oncology GroupNational Cancer Institute
|Elizabeth A. Raetz||Study Chair|
|Mitchell S. Cairo|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00098839
Information obtained from ClinicalTrials.gov on April 04, 2013
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