Therapy for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia - Full Text View

Purpose

The primary objective is to estimate the overall event-free survival of children at least one year of age at diagnosis who are treated with risk-directed therapy and to monitor the molecular remission induction rate.

Condition	Intervention	Phase
Lymphoblastic Leukemia, Acute	Drug: Prednisone, Dexamethasone, Vincristine, Daunorubicin Drug: Doxorubicin, L-asparaginase, PEG-L-asparaginase, Erwinia asparaginase Drug: Methotrexate, Cyclophosphamide, Cytarabine, Etoposide Drug: Mercaptopurine, Imatinib Procedure: chemotherapy, intrathecal chemotherapy Procedure: steroid therapy, hematopoietic stem cell transplantation	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia Steroids

Drug Information available for: Dexamethasone Cyclophosphamide Mercaptopurine Prednisone Methotrexate Cytarabine Dexamethasone acetate Vincristine sulfate Dexamethasone sodium phosphate Asparaginase Methotrexate sodium Daunorubicin Doxorubicin Daunorubicin hydrochloride Doxorubicin hydrochloride Etoposide Etoposide phosphate Pegaspargase Imatinib Imatinib mesylate Daunorubicin citrate

U.S. FDA Resources

Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:

Overall Event-free Survival (EFS) [ Time Frame: Median follow-up time (range) 5.6 (1.3 to 8.9) years ] [ Designated as safety issue: No ]
EFS was measured from the start of on-study to the date of first treatment failure of any kind (relapse, death, lineage switch, or second malignancy) or to the last date of follow-up. Failure to enter remission was considered an event at time zero. Measurement was determined by Kaplan-Meyer estimate.
Continuous Complete Remission Since Week 56 Therapy. [ Time Frame: Median follow up time (range) 4.5 (1 to 7.8) years ] [ Designated as safety issue: No ]
CCR was measured from end of week 56 therapy to the date of first treatment failure of any kind (relapse, death, lineage switch, or second malignancy) or to the last date of follow-up. Measurement was determined by Kaplan-Meyer estimate.

Secondary Outcome Measures:

Minimal Residual Disease (MRD) [ Time Frame: End of Induction (Day 46 MRD measurement) ] [ Designated as safety issue: No ]
Detection of MRD at end of induction where positive MRD was defined as one or more leukemic cell per 10,000 mononuclear bone-marrow cells (>=0.01%).
Mean Difference of Active Methotrexate Polyglutamates (MTXPG) in Leukemia Cells Between Two Arms (4 Hours vs. 24 Hours). [ Time Frame: 42 hours after start of high dose methotrexate infusion (HDMTX) ] [ Designated as safety issue: No ]
Children were randomly assigned to receive initial single-agent treatment with HDMTX (1g/m^2) as either a 24-hour infusion or a 4-hour infusion and the outcome measure was the accumulation of MTXPG in leukemia cells.
Circulating Leukemia Cells in Peripheral Blood Change From Prior to the Methotrexate Infusion to Three Days After Between Two Arms (4 Hours vs. 24 Hours) [ Time Frame: Immediately before the methotrexate infusion and three days after subsequent infusion ] [ Designated as safety issue: No ]
White blood cell (leukocytes) counts in peripheral blood by Complete Blood Count

Measurement: Percentage change of leukemia cells from baseline

Enrollment:	501
Study Start Date:	June 2000
Estimated Study Completion Date:	November 2020
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1	Drug: Prednisone, Dexamethasone, Vincristine, Daunorubicin See Detailed Description sections for details on treatment interventions. Drug: Doxorubicin, L-asparaginase, PEG-L-asparaginase, Erwinia asparaginase See Detailed Description sections for details on treatment interventions. Drug: Methotrexate, Cyclophosphamide, Cytarabine, Etoposide See Detailed Description sections for details on treatment interventions. Drug: Mercaptopurine, Imatinib See Detailed Description sections for details on treatment interventions. Procedure: chemotherapy, intrathecal chemotherapy See Detailed Description sections for details on treatment interventions. Procedure: steroid therapy, hematopoietic stem cell transplantation See Detailed Description sections for details on treatment interventions.
2	Drug: Prednisone, Dexamethasone, Vincristine, Daunorubicin See Detailed Description sections for details on treatment interventions. Drug: Doxorubicin, L-asparaginase, PEG-L-asparaginase, Erwinia asparaginase See Detailed Description sections for details on treatment interventions. Drug: Methotrexate, Cyclophosphamide, Cytarabine, Etoposide See Detailed Description sections for details on treatment interventions. Drug: Mercaptopurine, Imatinib See Detailed Description sections for details on treatment interventions. Procedure: chemotherapy, intrathecal chemotherapy See Detailed Description sections for details on treatment interventions. Procedure: steroid therapy, hematopoietic stem cell transplantation See Detailed Description sections for details on treatment interventions.

Arms

Assigned Interventions

1

Drug: Prednisone, Dexamethasone, Vincristine, Daunorubicin