Combination Chemotherapy With or Without Gemtuzumab in Treating Young Patients With Newly Diagnosed Acute Myeloid Leukemia
- Conditions
- Leukemia
- Interventions
- Registration Number
- NCT00372593
- Lead Sponsor
- Children's Oncology Group
- 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. Monoclonal antibodies, such as gemtuzumab, 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 gemtuzumab may kill more cancer cells. It is not yet known whether combination chemotherapy is more effective with or without gemtuzumab in treating patients with newly diagnosed acute myeloid leukemia.
PURPOSE: This randomized phase III trial is studying combination chemotherapy and gemtuzumab to see how well they work compared with combination chemotherapy alone in treating young patients with newly diagnosed acute myeloid leukemia.
- Detailed Description
OBJECTIVES:
Primary
* Compare the event-free survival (EFS) and overall survival (OS) of young patients with newly diagnosed acute myeloid leukemia (AML) treated with conventional combination chemotherapy with vs without gemtuzumab ozogamicin (GMTZ).
Secondary
* Compare the remission induction rates after two courses of therapy in these patients.
* Compare disease-free survival and OS in patients who are eligible for an human leukocyte antigen (HLA)-matched family donor (MFD) stem cell transplant (SCT) by virtue of their risk classification, with patients assigned to MFD SCT if a MFD is available, or to chemotherapy if a MFD is not available.
* Determine the outcome of patients with Down syndrome who are 4 years of age or older at diagnosis and treated with conventional combination chemotherapy without GMTZ.
* Compare the EFS and OS of patients with de novo AML treated with conventional combination chemotherapy with vs without GMTZ censoring MFD SCT recipients.
* Determine the prevalence and prognostic significance of molecular abnormalities of KIT, CCAAT-enhancer binding protein alpha (CEBPα) and MLL-Partial tandem duplications (PTD) genes in these patients.
* Determine the leukemic involvement of hematopoietic early progenitor and its role in defining response to therapy.
* Assess the ability of a second-generation flow cytometric assay to predict patients at high risk for relapse during periods of clinical remission.
* Examine whether GMTZ significantly improves EFS and OS in patients with higher CD33 concentrations/intensity.
* Examine whether GMTZ significantly improves complete remission, EFS, and OS in each of the cytogenetic risk groups (high-, intermediate-, and low-risk) identified in prior Medical Research Council trials.
* Utilize fluorescence in situ hybridization (FISH) analysis to identify variant patterns among subgroups of patients who demonstrate the same G-banded chromosomal abnormality (e.g., inv\[16\]/t\[16;16\], t\[8;21\], 11q23 abnormality) and determine whether these variant patterns account for the heterogeneity of responses to therapy.
* Examine the impact of complex karyotypes (≥ 3, ≥ 4, and ≥ 5 abnormalities) on OS and EFS in intermediate-risk patients for whom no high-risk or low-risk cytogenetic abnormalities exist.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to relapse risk (high vs intermediate vs low). Patients are randomized to 1 of 2 treatment arms. Patients with Down syndrome are nonrandomly assigned to arm I (but do not undergo allogeneic stem cell transplant \[SCT\]).
* Arm I (standard therapy):
* Induction 1: Patients receive cytarabine IT at the time of diagnosis or on day 1\*. Patients also receive cytarabine IV on days 1-10, daunorubicin hydrochloride IV over 6 hours on days 1, 3, and 5, and etoposide IV over 4 hours on days 1-5. After 3 weeks of rest, all patients (regardless of remission status) proceed to induction 2.
NOTE: \*Patients with Central Nervous System (CNS) disease receive cytarabine IT twice weekly until the cerebrospinal fluid is clear, followed by two additional IT treatments. Patients with refractory CNS leukemia after 6 doses of IT treatment are removed from the study.
* Induction 2: Patients receive cytarabine IT on day 1, cytarabine IV on days 1-8, daunorubicin hydrochloride IV over 6 hours on days 1, 3, and 5, and etoposide IV over 4 hours on days 1-5. After 3 weeks of rest, patients in complete remission (CR) proceed to intensification 1. Patients with refractory disease are removed from protocol therapy.
* Intensification 1: Patients receive cytarabine IT on day 1, high-dose cytarabine IV over 1 hour on days 1-5, and etoposide IV over 1 hour on days 1-5. After 3 weeks of rest, patients in remission proceed to intensification 2, followed by intensification 3. Patients in remission proceed to allogeneic SCT 2-8 weeks after blood counts recover. Patients with high-risk disease with an alternative donor proceed to intensification 2 and 3, followed by allogeneic SCT. Patients not in remission are removed from protocol therapy.
* Intensification 2: Patients receive cytarabine IT on day 1, high-dose cytarabine IV over 2 hours on days 1-4, and mitoxantrone hydrochloride IV over 1 hour on days 3-6. After 3 weeks of rest, patients proceed to intensification 3.
* Intensification 3: Patients receive high-dose cytarabine IV over 3 hours on days 1, 2, 8, and 9 and asparaginase intramuscularly on days 2 and 9.
* Arm II:
* Induction 1: Patients receive treatment as in induction 1 of arm I. Patients also receive gemtuzumab ozogamicin (GMTZ) IV over 2 hours on day 6.
* Induction 2: Patients receive treatment as in induction 2 of arm I.
* Intensification 1: Patients receive treatment as in intensification 1 of arm I.
* Intensification 2: Patients receive treatment as in intensification 2 of arm I. Patients also receive GMTZ IV over 2 hours on day 7.
* Intensification 3: Patients receive treatment as in intensification 3 of arm I.
* Allogeneic SCT (for patients with intermediate- or high-risk disease):
* MFD: Patients receive a conditioning regimen comprising busulfan IV over 2 hours every 6 hours on days -9 to -6 and cyclophosphamide IV over 1 hour on days -5 to -2. Patients undergo allogeneic SCT on day 0. Patients receive cyclosporine IV or orally twice daily on days -1 to 180 and methotrexate IV on days 1, 3, 6, and 11. Patients receive graft-vs-host disease (GVHD) prophylaxis comprising cyclosporine IV over 1-4 hours or orally twice daily on days -1 to 180 and methotrexate IV on days 1, 3, 6, and 11.
* Matched alternative donor: Patients receive a conditioning regimen comprising busulfan and cyclophosphamide as above. Patients also receive antithymocyte globulin IV over 6-8 hours on days -3 to -1. Patients then undergo allogeneic SCT and receive GVHD prophylaxis as above.
After completion of study treatment, patients are followed periodically for 3 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 1,012 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1070
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: Experimental - with GMTZ, AML Pts w/out Down Syndrome daunorubicin hydrochloride Pts receive IT ARA-C at diagnosis or on day 1 of treatment or twice a week for up to six doses. They also receive an infusion of ARA-C on days 1-10; a 6-hr infusion of daunorubicin on days 1, 3, \& 5; a 4-hr infusion of etoposide on days 1-5; and a 2-hr infusion of GMTZ - gemtuzumab ozogamicin (Mylotarg) on day 6. After 3 wks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 wks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hr infusion of mitoxantrone hydrochloride on days 3-6. They also receive a 2-hr infusion of gemtuzumab on day 7. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm A: Standard Arm - No GMTZ, AML Pts w/out Down Syndrome daunorubicin hydrochloride Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm B: Experimental - with GMTZ, AML Pts w/out Down Syndrome mitoxantrone hydrochloride Pts receive IT ARA-C at diagnosis or on day 1 of treatment or twice a week for up to six doses. They also receive an infusion of ARA-C on days 1-10; a 6-hr infusion of daunorubicin on days 1, 3, \& 5; a 4-hr infusion of etoposide on days 1-5; and a 2-hr infusion of GMTZ - gemtuzumab ozogamicin (Mylotarg) on day 6. After 3 wks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 wks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hr infusion of mitoxantrone hydrochloride on days 3-6. They also receive a 2-hr infusion of gemtuzumab on day 7. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm A: Standard Arm - No GMTZ, AML Pts w/out Down Syndrome mitoxantrone hydrochloride Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm A: Standard Arm - No GMTZ, AML Patients with Down Syndrome daunorubicin hydrochloride Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm A: Standard Arm - No GMTZ, AML Patients with Down Syndrome mitoxantrone hydrochloride Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm A: Standard Arm - No GMTZ, AML Pts w/out Down Syndrome asparaginase Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm A: Standard Arm - No GMTZ, AML Pts w/out Down Syndrome cytarabine Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm B: Experimental - with GMTZ, AML Pts w/out Down Syndrome cytarabine Pts receive IT ARA-C at diagnosis or on day 1 of treatment or twice a week for up to six doses. They also receive an infusion of ARA-C on days 1-10; a 6-hr infusion of daunorubicin on days 1, 3, \& 5; a 4-hr infusion of etoposide on days 1-5; and a 2-hr infusion of GMTZ - gemtuzumab ozogamicin (Mylotarg) on day 6. After 3 wks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 wks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hr infusion of mitoxantrone hydrochloride on days 3-6. They also receive a 2-hr infusion of gemtuzumab on day 7. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm B: Experimental - with GMTZ, AML Pts w/out Down Syndrome asparaginase Pts receive IT ARA-C at diagnosis or on day 1 of treatment or twice a week for up to six doses. They also receive an infusion of ARA-C on days 1-10; a 6-hr infusion of daunorubicin on days 1, 3, \& 5; a 4-hr infusion of etoposide on days 1-5; and a 2-hr infusion of GMTZ - gemtuzumab ozogamicin (Mylotarg) on day 6. After 3 wks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 wks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hr infusion of mitoxantrone hydrochloride on days 3-6. They also receive a 2-hr infusion of gemtuzumab on day 7. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm A: Standard Arm - No GMTZ, AML Pts w/out Down Syndrome etoposide Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm B: Experimental - with GMTZ, AML Pts w/out Down Syndrome etoposide Pts receive IT ARA-C at diagnosis or on day 1 of treatment or twice a week for up to six doses. They also receive an infusion of ARA-C on days 1-10; a 6-hr infusion of daunorubicin on days 1, 3, \& 5; a 4-hr infusion of etoposide on days 1-5; and a 2-hr infusion of GMTZ - gemtuzumab ozogamicin (Mylotarg) on day 6. After 3 wks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 wks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hr infusion of mitoxantrone hydrochloride on days 3-6. They also receive a 2-hr infusion of gemtuzumab on day 7. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm B: Experimental - with GMTZ, AML Pts w/out Down Syndrome gemtuzumab ozogamicin Pts receive IT ARA-C at diagnosis or on day 1 of treatment or twice a week for up to six doses. They also receive an infusion of ARA-C on days 1-10; a 6-hr infusion of daunorubicin on days 1, 3, \& 5; a 4-hr infusion of etoposide on days 1-5; and a 2-hr infusion of GMTZ - gemtuzumab ozogamicin (Mylotarg) on day 6. After 3 wks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 wks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hr infusion of mitoxantrone hydrochloride on days 3-6. They also receive a 2-hr infusion of gemtuzumab on day 7. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm A: Standard Arm - No GMTZ, AML Patients with Down Syndrome cytarabine Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm A: Standard Arm - No GMTZ, AML Patients with Down Syndrome asparaginase Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. Arm A: Standard Arm - No GMTZ, AML Patients with Down Syndrome etoposide Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin hydrochloride on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hr infusion of daunorubicin on days 1, 3, and 5; and a 4-hr infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hr infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hr infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hr infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9.
- Primary Outcome Measures
Name Time Method Event-free Survival at 3 Years Time from study entry to time of induction failure, relapse, or death, assessed at 3 years The Kaplan-Meier method will be used to calculate estimates of Event Free Survival (EFS). The log-rank test will be used to compare survival between treatment groups. Analysis of EFS of Down syndrome patients will be performed separately. Monitoring for efficacy of GMTZ with respect to Overall Survival (OS) and EFS will utilize monitoring based on the Lan-DeMets criterion with α-spending function αt\^2 (truncated at 3 standard deviations) and 2.5% type I error.
Overall Survival at 3 Years Time from study entry, assessed at 3 years The Kaplan-Meier method will be used to calculate estimates of OS. Analysis of OS of Down syndrome patients will be performed separately. Monitoring for efficacy of GMTZ with respect to OS and EFS will utilize monitoring based on the Lan-DeMets criterion with α-spending function αt\^2 (truncated at 3 standard deviations) and 2.5% type I error.
- Secondary Outcome Measures
Name Time Method Time to Marrow Recovery At 25 days after treatment with Induction I, Induction II, and Intensification I Mean time to ANC recovery - defined as ANC greater than 500/MicroLiter for 3 consecutive days.
Disease-free Survival (DFS) At 3 years from end of Intensification I Time from end of Intensification I to relapse, death or last contact
Toxicities, Including Infectious Complications From the time therapy is initiated, assessed up to 10 years Number of participants with at least one grade 3 or higher adverse event during therapy.
Remission Induction Rate After 2 Courses of Induction Therapy After 2 courses of induction (I and II) therapy, assessed for up to 10 years Patients without an evaluable bone marrow at the end of Induction I will be excluded from the calculation of remission rate after 2 courses of therapy because their responses are not evaluable. The following patients will be considered to not be in complete remission (CR) after 2 courses of therapy: (1) patients who die during Induction I and II; (2) patients with ≥ 5% blasts or extramedullary disease at the end of Induction II.
Mortality During the first three courses of therapy Number of participants who died during the first three courses of therapy.
Trial Locations
- Locations (198)
University of Illinois Cancer Center
🇺🇸Chicago, Illinois, United States
Childrens Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Kaiser Permanente Medical Center - Oakland
🇺🇸Oakland, California, United States
Alfred I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Southern California Permanente Medical Group
🇺🇸Downey, California, United States
Memorial Cancer Institute at Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
University of South Alabama Mitchell Cancer Institute
🇺🇸Mobile, Alabama, United States
Banner Desert Medical Center
🇺🇸Mesa, Arizona, United States
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Arizona Cancer Center at University of Arizona Health Sciences Center
🇺🇸Tucson, Arizona, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
CCOP - Scott and White Hospital
🇺🇸Temple, Texas, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Sanford Cancer Center at Sanford USD Medical Center
🇺🇸Sioux Falls, South Dakota, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Westmead Institute for Cancer Research at Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
🇺🇸Dallas, Texas, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, Texas, United States
Children's Hospital of Western Ontario
🇨🇦London, Ontario, Canada
Centre Hospitalier Universitaire de Quebec
🇨🇦Quebec, Canada
Women's and Children's Hospital
🇦🇺North Adelaide, South Australia, Australia
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Starship Children's Health
🇳🇿Grafton, New Zealand
Baylor University Medical Center - Houston
🇺🇸Houston, Texas, United States
University of Miami Sylvester Comprehensive Cancer Center - Miami
🇺🇸Miami, Florida, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
St. Vincent Indianapolis Hospital
🇺🇸Indianapolis, Indiana, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
Jonsson Comprehensive Cancer Center at UCLA
🇺🇸Los Angeles, California, United States
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
CCOP - MeritCare Hospital
🇺🇸Fargo, North Dakota, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
Children's Hospital and Research Center Oakland
🇺🇸Oakland, California, United States
Santa Barbara Cottage Children's Hospital
🇺🇸Santa Barbara, California, United States
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
🇺🇸Torrance, California, United States
Broward General Medical Center Cancer Center
🇺🇸Fort Lauderdale, Florida, United States
Miami Children's Hospital
🇺🇸Miami, Florida, United States
Baptist-South Miami Regional Cancer Program
🇺🇸Miami, Florida, United States
Sacred Heart Cancer Center at Sacred Heart Hospital
🇺🇸Pensacola, Florida, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Kaplan Cancer Center at St. Mary's Medical Center
🇺🇸West Palm Beach, Florida, United States
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
🇺🇸Atlanta, Georgia, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
MBCCOP - Medical College of Georgia Cancer Center
🇺🇸Augusta, Georgia, United States
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Tripler Army Medical Center
🇺🇸Tripler AMC, Hawaii, United States
Mountain States Tumor Institute at St. Luke's Regional Medical Center
🇺🇸Boise, Idaho, United States
Children's Memorial Hospital - Chicago
🇺🇸Chicago, Illinois, United States
Cardinal Bernardin Cancer Center at Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
Advocate Christ Medical Center
🇺🇸Oak Lawn, Illinois, United States
Keyser Family Cancer Center at Advocate Hope Children's Hospital
🇺🇸Oak Lawn, Illinois, United States
Advocate Lutheran General Cancer Care Center
🇺🇸Park Ridge, Illinois, United States
Simmons Cooper Cancer Institute
🇺🇸Springfield, Illinois, United States
Holden Comprehensive Cancer Center at University of Iowa
🇺🇸Iowa City, Iowa, United States
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Greenebaum Cancer Center at University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Floating Hospital for Children at Tufts - New England Medical Center
🇺🇸Boston, Massachusetts, United States
Baystate Regional Cancer Program at D'Amour Center for Cancer Care
🇺🇸Springfield, Massachusetts, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
UMASS Memorial Cancer Center - University Campus
🇺🇸Worcester, Massachusetts, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Butterworth Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
🇺🇸Grosse Pointe Woods, Michigan, United States
CCOP - Kalamazoo
🇺🇸Kalamazoo, Michigan, United States
Breslin Cancer Center at Ingham Regional Medical Center
🇺🇸Lansing, Michigan, United States
Ellis Fischel Cancer Center at University of Missouri - Columbia
🇺🇸Columbia, Missouri, United States
Masonic Cancer Center at University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Albany Medical Center Hospital
🇺🇸Albany, New York, United States
Brooklyn Hospital Center
🇺🇸Brooklyn, New York, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Schneider Children's Hospital
🇺🇸New Hyde Park, New York, United States
New York Weill Cornell Cancer Center at Cornell University
🇺🇸New York, New York, United States
NYU Cancer Institute at New York University Medical Center
🇺🇸New York, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
🇺🇸New York, New York, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
🇺🇸Rochester, New York, United States
SUNY Upstate Medical University Hospital
🇺🇸Syracuse, New York, United States
Stony Brook University Cancer Center
🇺🇸Stony Brook, New York, United States
Mission Hospitals - Memorial Campus
🇺🇸Asheville, North Carolina, United States
Presbyterian Cancer Center at Presbyterian Hospital
🇺🇸Charlotte, North Carolina, United States
Blumenthal Cancer Center at Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Duke Comprehensive Cancer Center
🇺🇸Durham, North Carolina, United States
Leo W. Jenkins Cancer Center at ECU Medical School
🇺🇸Greenville, North Carolina, United States
Akron Children's Hospital
🇺🇸Akron, Ohio, United States
Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Children's Medical Center - Dayton
🇺🇸Dayton, Ohio, United States
Toledo Hospital
🇺🇸Toledo, Ohio, United States
Medical University of Ohio Cancer Center
🇺🇸Toledo, Ohio, United States
Oklahoma University Cancer Institute
🇺🇸Oklahoma City, Oklahoma, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Geisinger Cancer Institute at Geisinger Health
🇺🇸Danville, Pennsylvania, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
St. Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Palmetto Health South Carolina Cancer Center
🇺🇸Columbia, South Carolina, United States
Texas Tech University Health Sciences Center School of Medicine - Amarillo
🇺🇸Amarillo, Texas, United States
Naval Medical Center - Portsmouth
🇺🇸Portsmouth, Virginia, United States
Mary Bridge Children's Hospital and Health Center - Tacoma
🇺🇸Tacoma, Washington, United States
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
St. Vincent Hospital Regional Cancer Center
🇺🇸Green Bay, Wisconsin, United States
Royal Children's Hospital
🇦🇺Herston, Queensland, Australia
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
UAB Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Legacy Emanuel Hospital and Health Center and Children's Hospital
🇺🇸Portland, Oregon, United States
Knight Cancer Institute at Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Tulane Cancer Center Office of Clinical Research
🇺🇸Alexandria, Louisiana, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
St. Joseph's Hospital and Medical Center
🇺🇸Paterson, New Jersey, United States
Maine Children's Cancer Program at Barbara Bush Children's Hospital
🇺🇸Portland, Maine, United States
Swiss Pediatric Oncology Group Geneva
🇨🇭Geneva, Switzerland
Janeway Children's Health and Rehabilitation Centre
🇨🇦Saint John's, Newfoundland and Labrador, Canada
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
East Tennessee Children's Hospital
🇺🇸Knoxville, Tennessee, United States
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
CancerCare of Maine at Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
West Virginia University Health Sciences Center - Charleston
🇺🇸Charleston, West Virginia, United States
Walter Reed Army Medical Center
🇺🇸Washington, District of Columbia, United States
University of Mississippi Cancer Clinic
🇺🇸Jackson, Mississippi, United States
T.C. Thompson Children's Hospital
🇺🇸Chattanooga, Tennessee, United States
CCOP - Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
Fletcher Allen Health Care - University Health Center Campus
🇺🇸Burlington, Vermont, United States
San Jorge Children's Hospital
🇵🇷Santurce, Puerto Rico
Greenville Hospital Cancer Center
🇺🇸Greenville, South Carolina, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Hopital Sainte Justine
🇨🇦Montreal, Quebec, Canada
Swiss Pediatric Oncology Group Bern
🇨🇭Bern, Switzerland
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Cancer Centre of Southeastern Ontario at Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
Cardinal Glennon Children's Hospital
🇺🇸Saint Louis, Missouri, United States
Children's Hospital Center for Cancer and Blood Disorders
🇺🇸Aurora, Colorado, United States
St. Joseph's Cancer Institute at St. Joseph's Hospital
🇺🇸Tampa, Florida, United States
Children's Hospital
🇺🇸Omaha, Nebraska, United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Midwest Children's Cancer Center at Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Lee Cancer Care of Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
Rhode Island Hospital Comprehensive Cancer Center
🇺🇸Providence, Rhode Island, United States
Cook Children's Medical Center - Fort Worth
🇺🇸Fort Worth, Texas, United States
Carilion Medical Center for Children at Roanoke Community Hospital
🇺🇸Roanoke, Virginia, United States
Providence Cancer Center at Sacred Heart Medical Center
🇺🇸Spokane, Washington, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Sutter Cancer Center
🇺🇸Sacramento, California, United States
University of California Davis Cancer Center
🇺🇸Sacramento, California, United States
C.S. Mott Children's Hospital at University of Michigan Medical Center
🇺🇸Ann Arbor, Michigan, United States
Wake Forest University Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States
Madigan Army Medical Center - Tacoma
🇺🇸Tacoma, Washington, United States
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
Hackensack University Medical Center Cancer Center
🇺🇸Hackensack, New Jersey, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Florida Hospital Cancer Institute at Florida Hospital Orlando
🇺🇸Orlando, Florida, United States
M.D. Anderson Cancer Center at Orlando
🇺🇸Orlando, Florida, United States
Nemours Children's Clinic - Orlando
🇺🇸Orlando, Florida, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Hollings Cancer Center at Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Cancer Research Center of Hawaii
🇺🇸Honolulu, Hawaii, United States
University of Florida Shands Cancer Center
🇺🇸Gainesville, Florida, United States
Lucille P. Markey Cancer Center at University of Kentucky
🇺🇸Lexington, Kentucky, United States
Children's Hospital of New Orleans
🇺🇸New Orleans, Louisiana, United States
Blank Children's Hospital
🇺🇸Des Moines, Iowa, United States
Dell Children's Medical Center of Central Texas
🇺🇸Austin, Texas, United States
Albert Einstein Cancer Center at Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸Richmond, Virginia, United States
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Children's & Women's Hospital of British Columbia
🇨🇦Vancouver, British Columbia, Canada
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Overlook Hospital
🇺🇸Summit, New Jersey, United States