Therapy for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
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ClinicalTrials.gov Identifier: NCT00137111 |
Recruitment Status :
Completed
First Posted : August 29, 2005
Results First Posted : April 26, 2011
Last Update Posted : September 11, 2020
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Condition or disease | Intervention/treatment | 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 (Clinical Trial) |
Actual Enrollment : | 501 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia |
Actual Study Start Date : | July 8, 2000 |
Actual Primary Completion Date : | November 2010 |
Actual Study Completion Date : | April 2014 |

Arm | Intervention/treatment |
---|---|
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. |
- Overall Event-free Survival (EFS) [ Time Frame: Median follow-up time (range) 5.6 (1.3 to 8.9) years ]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 ]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.
- Minimal Residual Disease (MRD) [ Time Frame: End of Induction (Day 46 MRD measurement) ]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) ]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 ]
White blood cell (leukocytes) counts in peripheral blood by Complete Blood Count
Measurement: Percentage change of leukemia cells from baseline
- Median Difference in CASP1 Gene Expression in Primary Leukemia Cells of Patients in Glucocorticoid-resistant Cells vs Glucocorticoid-sensitive Cells [ Time Frame: Pre-treatment ]Prednisolone sensitivity was measured in primary leukemia cells from bone marrow collected at diagnosis. Expression of CASP1 was determined by HG-U133A microarray. Values given are gene expression values, and the unit is arbitrary units (AU) defined as scaled fluorescence measured on microarray.
- Median Difference in NLRP3 Gene Expression in Primary Leukemia Cells of Patients in Glucocorticoid-resistant Cells vs. Glucocorticoid-sensitive Cells [ Time Frame: Pre-treatment ]Prednisolone sensitivity was measured in primary leukemia cells from bone marrow collected at diagnosis. Expression of NLRP3 was determined by HG-U133A microarray. Values given are gene expression values, and the unit is arbitrary units (AU) defined as scaled fluorescence measured on microarray.

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Ages Eligible for Study: | 12 Months to 18 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Diagnosis of non-B-cell ALL by immunophenotyping, as determined by the reactivity pattern to a panel of monoclonal antibodies with flow cytometry as well as morphology and cytochemical staining.
- Age range: 1 to 18 years (inclusive).
Exclusion Criteria:
• Previously treated with chemotherapy for one week or longer.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00137111
United States, Tennessee | |
St Jude Children's Research Hospital | |
Memphis, Tennessee, United States, 38105 | |
United States, Texas | |
Cook Children's Medical Center | |
Fort Worth, Texas, United States, 76104 |
Principal Investigator: | Ching-Hon Pui, M.D. | St. Jude Children's Research Hospital |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | St. Jude Children's Research Hospital |
ClinicalTrials.gov Identifier: | NCT00137111 |
Other Study ID Numbers: |
TOTXV R37CA036401 ( U.S. NIH Grant/Contract ) P30CA021765 ( U.S. NIH Grant/Contract ) F32CA141762 ( U.S. NIH Grant/Contract ) |
First Posted: | August 29, 2005 Key Record Dates |
Results First Posted: | April 26, 2011 |
Last Update Posted: | September 11, 2020 |
Last Verified: | September 2020 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Leukemia |
Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine Dexamethasone Prednisone Cyclophosphamide Doxorubicin Methotrexate |
Etoposide Vincristine Daunorubicin Asparaginase Mercaptopurine Pegaspargase Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists |