Clincosm LogoSign in Get a demo

Therapy for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia

Sponsor
St. Jude Children's Research Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT00137111
Collaborator
National Cancer Institute (NCI) (NIH)
501
Enrollment
2
Locations
2
Arms
164.8
Actual Duration (Months)
250.5
Patients Per Site
1.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
  • 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

Detailed Description

These are the following secondary objectives:

  • To determine if CNS irradiation can be safely omitted in the context of the systemic therapy used in the protocol.

  • To identify whether prolonged (24 hour) intravenous infusions of HDMTX produce greater methotrexate polyglutamate (MTXPG) accumulation than short (4 hour) infusions 42 hours after 1 gm/m2 of HDMTX, stratified for lineage (T- vs B-lineage) and ploidy (hyperdiploid vs non-hyperdiploid B-lineage).

  • To determine whether prolonged (24 hour) intravenous infusions of HDMTX produce greater antileukemic effects than short (4 hour) infusions, based on the inhibition of de novo purine synthesis in bone marrow blasts and the decrease in circulating blasts during the 4 day "window" prior to initiation of conventional remission induction therapy.

  • MRD

  • Other exploratory objectives

Details of Treatment Plan

Treatment will consist of three main phases, Remission Induction, Consolidation, and Continuation. Treatment with an Upfront HDMTX Window for research purposes will be optional.

All patients will receive IT therapy on day 1, dose is age dependent.

Upfront High-Dose Methotrexate Window

HDMTX (1 g/m2) as a 4 hour infusion versus as a 24 hour infusion. Leucovorin rescue will be given.

Remission Induction

Prednisone 40 mg/m2/day PO Days 5 - 32 Vincristine 1.5 mg/m2/week IV Days 5, 12, 19, 26 Daunorubicin 25 mg/m2/week IV Days 5, 12 L-asparaginase 10,000 Unit/m2/dose IM Days 6, 8, 10, 12, 14, 16 (19, 21, 23) Cyclophosphamide 1000 mg/m2/dose IV Day 26 Cytarabine 75 mg/m2/dose IV Days 27-30, 34-37 6-Mercaptopurine 60 mg/m2/dose PO Days 26-39 Imatinib 40 mg/m2 bid for Ph positive patients starting Day 22 of induction. Intrathecal therapy will be administered on day 1 and 19, dose age dependent. Patients with high risk of CNS relapse will receive additional IT treatments on days 8 and 26.

Consolidation Treatment

High dose methotrexate targeted dose depending on risk status, days 1, 15, 29, and 43 and mercaptopurine 50 mg/m2/day, days 1-56.

Reintensification treatment for patients with high risk disease:

Patients with high risk disease will be offered the option of hematopoietic stem cell transplant (HSCT) and may receive an additional 1-2 cycles of reintensification treatment prior to maximize the anti-leukemic kill before transplant.

Dexamethasone 20 mg/m2 PO days 1-3 Cytarabine 2 g/m2 IV x 4 doses, days 3-5 Etoposide 100 mg/m2 IV x 5 doses, days 3-5 L-asparaginase 25,000 Units/m2 IM day 6 Intrathecal treatment Day 5

Continuation Treatment (lasts 120 weeks for girls and 146 weeks for boys)

Treatment will depend on risk classification: low versus standard versus high risk

Treatment weeks 1 to 20:

Week Standard/High Risk Low Risk

  1. DEX + DOX + VCR + 6MP + ASP 6MP + DEX + VCR

  2. 6MP + ASP 6MP + MTX

  3. 6MP + ASP 6MP + MTX

  4. DEX + DOX + VCR + 6MP + ASP 6MP + DEX + VCR

  5. 6MP + ASP 6MP + MTX

  6. 6MP + ASP 6MP + MTX

  7. Reinduction I§ Reinduction I

  8. Reinduction I Reinduction I

  9. Reinduction I Reinduction I

  10. 6MP + ASP 6MP + MTX

  11. DOX + VCR + 6MP + ASP 6MP + MTX

  12. 6MP + ASP 6MP + MTX

  13. 6MP + ASP 6MP + MTX

  14. DEX + DOX + VCR + 6MP + ASP 6MP + DEX + VCR

  15. 6MP + ASP 6MP + MTX

  16. 6MP + ASP 6MP + MTX

  17. Reinduction II Reinduction II

  18. Reinduction II Reinduction II

  19. Reinduction II Reinduction II

  20. No chemotherapy 6MP + MTX

Dexamethasone 12 mg/m2 (std/high risk) or 8 mg/m2 (low risk) PO daily (tid) x 5 days, Days 1-5 Doxorubicin 30 mg/m2 IV, Day 1 Vincristine 2.0 mg/m2 IV push (max. 2 mg), Day 1 Mercaptopurine 50 mg/m2 PO daily x 7 days (std/high risk), Days 1-7 75 mg/m2 PO daily x 7 days (low risk), Days 1-7 L-asparaginase 25,000 Unit/m2 IM, Day 1 Methotrexate 40 mg/m2 IV or IM, Day 1

Reinduction I and II

This phase of treatment will be started at weeks 7 and 17 after bone marrow examination confirms complete remission. Reinduction treatment will be given twice: weeks 7 to 9 and weeks 17 to 19 for all patients.

Reinduction I for Standard/High Risk ALL:

Dexamethasone 8 mg/m2/day PO (t.i.d.) Days 1-8, 15, 21, Vincristine 1.5 mg/m2/week IV (max 2 mg) Days 1, 8, 15, Doxorubicin 30 mg/m2 Days 1, 8, L-asparaginase 25,000 Unit/m2 IM Days 1, 8, 15, Intrathecal chemotherapy, dose age dependent Day 1.

Reinduction II for Standard/High Risk ALL:

Dexamethasone 8 mg/m2/day PO (t.i.d.) Days 1-8, 15-21, Vincristine 1.5 mg/m2/week IV (max 2 mg) Days 1, 8, 15, L-asparaginase 25,000 Unit/m2, weekly IM Days 1, 8, 17, Intrathecal chemotherapy, dose age dependent Day 1 High-dose cytarabine 2 gm/m2 IV q 12 Days 15, 16

Reinduction I and II for Low Risk ALL Dexamethasone 8 mg/m2/day PO (t.i.d.) Days 1-8, 15-21 Vincristine 1.5 mg/m2/week IV (max 2 mg), Days 1, 8, 15 L-asparaginase 10,000 Unit/m2/thrice weekly IM Days 2, 4, 6, 8, 10, 12, 15, 17, 19 Doxorubicin 30 mg/m2/week IV Day 1 Intrathecal chemotherapy, dose age dependent on Day 1

Treatment Weeks 21 to end of therapy Week Standard/High Risk Low Risk

  1. 6MP + MTX 6MP + MTX

  2. 6MP + MTX 6MP + MTX

  3. Cyclo + Ara-C 6MP + MTX

  4. DEX + VCR 6MP + DEX + VCR

  5. 6MP + MTX 6MP + MTX

  6. 6MP + MTX 6MP + MTX

  7. Cyclo + Ara-C 6MP + MTX

  8. DEX + VCR 6MP + DEX + VCR

Mercaptopurine 75 mg/m2 PO, daily x 7 days, Days 1-7 Methotrexate 40 mg/m2 IV or IM, Day 1 Cyclophosphamide 300 mg/m2 IV, Day 1 Cytarabine 300 mg/m2 IV, Day 1 Dexamethasone 12 mg/m2 (std/high risk) or 8 mg/m2 (low risk) PO daily (tid) x 5, Day 1-5 Vincristine 2.0 mg/m2 IV push (max. 2 mg), Day 1

The same treatment (weeks 21-28) will be repeated for a total of 6 times (until week 68). After week 68, all patients will receive daily 6MP and weekly MTX with pulses of dexamethasone and vincristine every 4 weeks until week 100, after which only 6MP and methotrexate will be given. Intrathecal treatment will be given every 8 weeks only to patients at high risk of CNS relapse after week 48 and will be discontinued after week 96. Continuation therapy will be discontinued after 120 weeks in girls and after 146 weeks in boys

Patients who meet the criteria of high-risk ALL are candidates for allogeneic hematopoietic stem cell transplantation. However, if the option is declined by the patients or guardians, or the procedure is deemed unsuitable by the attending physician and the principal investigator, the patient will remain on study and continue to receive chemotherapy

Study Design

Study Type:
Interventional
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 :
Jul 8, 2000
Actual Primary Completion Date :
Nov 1, 2010
Actual Study Completion Date :
Apr 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Other: 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.
Other: 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.

Outcome Measures

Primary Outcome Measures

  1. Overall Event-free Survival (EFS) [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.

  2. Continuous Complete Remission Since Week 56 Therapy. [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.

Secondary Outcome Measures

  1. Minimal Residual Disease (MRD) [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%).

  2. Mean Difference of Active Methotrexate Polyglutamates (MTXPG) in Leukemia Cells Between Two Arms (4 Hours vs. 24 Hours). [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.

  3. 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) [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

Other Outcome Measures

  1. Median Difference in CASP1 Gene Expression in Primary Leukemia Cells of Patients in Glucocorticoid-resistant Cells vs Glucocorticoid-sensitive Cells [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.

  2. Median Difference in NLRP3 Gene Expression in Primary Leukemia Cells of Patients in Glucocorticoid-resistant Cells vs. Glucocorticoid-sensitive Cells [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
12 Months to 18 Years
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 St Jude Children's Research Hospital Memphis Tennessee United States 38105
2 Cook Children's Medical Center Fort Worth Texas United States 76104

Sponsors and Collaborators

  • St. Jude Children's Research Hospital
  • National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Ching-Hon Pui, M.D., St. Jude Children's Research Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00137111
Other Study ID Numbers:
  • TOTXV
  • R37CA036401
  • P30CA021765
  • F32CA141762
First Posted:
Aug 29, 2005
Last Update Posted:
Sep 11, 2020
Last Verified:
Sep 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by St. Jude Children's Research Hospital
Leukemia
Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Cytarabine
Dexamethasone
Prednisone
Cyclophosphamide
Doxorubicin
Methotrexate
Etoposide
Vincristine
Daunorubicin
Asparaginase
Mercaptopurine
Pegaspargase

Study Results

Participant Flow

Recruitment Details 501 patients were recruited between June 2000 and October 2007.
Pre-assignment Detail 501 patients were enrolled on the study. 3 patients were determined to be ineligible shortly after enrollment (wrong diagnosis - AML or CML in blast crisis).498 patients started the study.
Arm/Group Title Total Therapy 4 hr 24 hr Non Randomized
Arm/Group Description Total therapy applies to all eligible patients and includes remission induction, consolidation, and continuation therapy. 4 hour High-Dose Methotrexate Infusion in upfront window treatment 24 hour High-Dose Methotrexate Infusion in upfront window treatment Patients not randomized for window study
Period Title: Window Therapy
STARTED 0 176 180 142
COMPLETED 0 176 180 142
NOT COMPLETED 0 0 0 0
Period Title: Window Therapy
STARTED 498 0 0 0
COMPLETED 458 0 0 0
NOT COMPLETED 40 0 0 0

Baseline Characteristics

Arm/Group Title Total Therapy 4 hr 24 hr Non Randomized Total
Arm/Group Description Total therapy applies to all eligible patients and includes remission induction, consolidation, and continuation therapy. 4 hour High-Dose Methotrexate Infusion in upfront window treatment 24 hour High-Dose Methotrexate Infusion in upfront window treatment Patients not randomized for window study Total of all reporting groups
Overall Participants 498 0 0 0 498
Age, Customized (participants) [Number]
1 to 9 years
372
74.7%
372
Infinity
>=10 years
126
25.3%
126
Infinity
Sex: Female, Male (Count of Participants)
Female
219
44%
219
Infinity
Male
279
56%
279
Infinity

Outcome Measures

1. Primary Outcome
Title Overall Event-free Survival (EFS)
Description 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.
Time Frame Median follow-up time (range) 5.6 (1.3 to 8.9) years

Outcome Measure Data

Analysis Population Description
498 enrolled patients were eligible for analysis to estimate the overall event-free survival of children at least one year of age at diagnosis who are treated with risk-directed therapy.
Arm/Group Title Total Therapy
Arm/Group Description Total therapy applies to all eligible patients.
Measure Participants 498
Number [Percentage of Participants]
87.3
17.5%
2. Primary Outcome
Title Continuous Complete Remission Since Week 56 Therapy.
Description 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.
Time Frame Median follow up time (range) 4.5 (1 to 7.8) years

Outcome Measure Data

Analysis Population Description
Patients meeting the following high risk CNS Relapse criteria: white cell blood cell count at diagnosis more than 100,000; Philadelphia Chromosome Positive; CNS 3 at diagnosis; T-Lineage with white blood cell count more than 50,000.
Arm/Group Title Patients With High Risk of CNS Relapse
Arm/Group Description This is a subset of all patients enrolled. It is not a specific treatment arm.
Measure Participants 70
Number [Percentage of participants]
92.2
18.5%
3. Secondary Outcome
Title Minimal Residual Disease (MRD)
Description 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%).
Time Frame End of Induction (Day 46 MRD measurement)

Outcome Measure Data

Analysis Population Description
Patients who completed induction and had successful MRD studies on day 46.
Arm/Group Title Total Therapy
Arm/Group Description Total therapy applies to all eligible patients.
Measure Participants 492
Negative <0.01%
390
78.3%
Positive >= 0.01%
102
20.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Total Therapy
Comments Of the 498 eligible patients, 492 were successfully evaluated with day 46 MRD measurement.
Type of Statistical Test Superiority or Other (legacy)
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Binomial proportion
Estimated Value 79.27
Confidence Interval (2-Sided) 95%
75.69 to 82.85
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Mean Difference of Active Methotrexate Polyglutamates (MTXPG) in Leukemia Cells Between Two Arms (4 Hours vs. 24 Hours).
Description 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.
Time Frame 42 hours after start of high dose methotrexate infusion (HDMTX)

Outcome Measure Data

Analysis Population Description
The 286 patients randomized to treatment with high-dose methotrexate (HDMTX) who had methotrexate polyglutamate (MTXPG) concentration measured in bone marrow ALL cells .
Arm/Group Title 4 hr 24 hr
Arm/Group Description 4 hour High-Dose Methotrexate Infusion in upfront window treatment 24 hour High-Dose Methotrexate Infusion in upfront window treatment
Measure Participants 136 150
Mean (Standard Deviation) [pmol/1,000,000,000 cells]
1688
(2015)
2521
(2950)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Total Therapy, 24 hr
Comments t-test stratified for lineage and ploidy
Type of Statistical Test Superiority or Other (legacy)
Comments
Statistical Test of Hypothesis p-Value .0062
Comments p-value from t-test after stratified for lineage and ploidy
Method t-test, 2 sided
Comments
5. Secondary Outcome
Title 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)
Description White blood cell (leukocytes) counts in peripheral blood by Complete Blood Count Measurement: Percentage change of leukemia cells from baseline
Time Frame Immediately before the methotrexate infusion and three days after subsequent infusion

Outcome Measure Data

Analysis Population Description
Three hundred twenty (320) patients were evaluable to assess the influence of infusion duration on methotrexate's antileukemic effects.
Arm/Group Title 4 hr 24 hr
Arm/Group Description 4 hour High-Dose Methotrexate Infusion in upfront window treatment 24 hour High-Dose Methotrexate Infusion in upfront window treatment
Measure Participants 156 164
Mean (Standard Deviation) [Percent change]
-44
(42.2)
-50
(35.5)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Total Therapy, 24 hr
Comments t-test adjusting for lineage and ploidy
Type of Statistical Test Superiority or Other (legacy)
Comments
Statistical Test of Hypothesis p-Value .15
Comments p-value from t-test after adjusted for lineage and ploidy
Method t-test, 2 sided
Comments
6. Other Pre-specified Outcome
Title Median Difference in CASP1 Gene Expression in Primary Leukemia Cells of Patients in Glucocorticoid-resistant Cells vs Glucocorticoid-sensitive Cells
Description 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.
Time Frame Pre-treatment

Outcome Measure Data

Analysis Population Description
One hundred forty-four (144) patients were evaluable to assess prednisolone sensitivity measured in bone marrow ALL cells and CASP1 expression in RNA by MTT assay.
Arm/Group Title Total Therapy
Arm/Group Description Total therapy applies to all eligible patients.
Measure Participants 144
Prednisolone-sensitive cells
341.3
Prednisolone-resistant cells
447.9
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Total Therapy
Comments
Type of Statistical Test Superiority or Other (legacy)
Comments
Statistical Test of Hypothesis p-Value 0.00000095
Comments
Method Wilcoxon (Mann-Whitney)
Comments
7. Other Pre-specified Outcome
Title Median Difference in NLRP3 Gene Expression in Primary Leukemia Cells of Patients in Glucocorticoid-resistant Cells vs. Glucocorticoid-sensitive Cells
Description 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.
Time Frame Pre-treatment

Outcome Measure Data

Analysis Population Description
One hundred forty-four (144) patients were evaluable to assess prednisolone sensitivity measured in bone marrow ALL cells and NLRP3 expression in RNA by MTT assay
Arm/Group Title Total Therapy
Arm/Group Description Total therapy applies to all eligible patients.
Measure Participants 144
Prednisolone-sensitive cells
41.2
Prednisolone-resistant cells
110.7
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Total Therapy
Comments
Type of Statistical Test Superiority or Other (legacy)
Comments
Statistical Test of Hypothesis p-Value 0.0000007
Comments
Method Wilcoxon (Mann-Whitney)
Comments

Adverse Events

Time Frame Participants were monitored from the start of therapy through 30 days after this protocol's treatment plan was completed.
Adverse Event Reporting Description
Arm/Group Title Total Therapy
Arm/Group Description Total therapy applies to all eligible patients.
All Cause Mortality
Total Therapy
Affected / at Risk (%) # Events
Total / (NaN)
Serious Adverse Events
Total Therapy
Affected / at Risk (%) # Events
Total 74/498 (14.9%)
Blood and lymphatic system disorders
CNS hemorrhage/bleeding 2/498 (0.4%) 2
DIC (disseminated intravascular coagulation) 2/498 (0.4%) 2
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia 1/498 (0.2%) 1
Cardiac disorders
Hypertension 2/498 (0.4%) 2
Hypotension 9/498 (1.8%) 9
Sinus tachycardia 1/498 (0.2%) 1
Supraventricular arrhythmias (SVT/atrial fibrillation/flutter) 1/498 (0.2%) 1
Thrombosis/embolism 5/498 (1%) 5
Eye disorders
Vision-blurred vision 1/498 (0.2%) 1
Gastrointestinal disorders
Colitis 4/498 (0.8%) 4
Pancreatitis 2/498 (0.4%) 2
Renal failure 4/498 (0.8%) 4
Typhlitis (inflammation of cecum) 2/498 (0.4%) 2
Vomiting 1/498 (0.2%) 1
General disorders
Edema 2/498 (0.4%) 2
Fever (in the absence of neutropenia, where neutropenia is defined as AGC<1.0 x 10e9/L) 3/498 (0.6%) 3
Hepatobiliary disorders
Bilirubin 1/498 (0.2%) 1
Hepatic-Other 1/498 (0.2%) 1
Liver dysfunction/failure (clinical), 2/498 (0.4%) 2
Immune system disorders
Allergic Reaction to Asparaginase 6/498 (1.2%) 6
Allergic reaction/hypersensitivity (including drug fever) 2/498 (0.4%) 2
Infections and infestations
Catheter-related infection 3/498 (0.6%) 3
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe 3/498 (0.6%) 4
Infection (documented clinically or microbiologically) with grade 3 or 4 neutropenia (ANC <1.0 x 10e 32/498 (6.4%) 32
Infection without neutropenia 5/498 (1%) 5
Metabolism and nutrition disorders
Acidosis (metabolic or respiratory) 2/498 (0.4%) 2
Amylase 1/498 (0.2%) 1
Hyperglycemia 1/498 (0.2%) 1
Hyperkalemia 1/498 (0.2%) 1
Lipase 1/498 (0.2%) 1
Nervous system disorders
Leukoencephalopathy associated with radiological findings 2/498 (0.4%) 2
Neuropathy-sensory 1/498 (0.2%) 1
Seizure(s) 6/498 (1.2%) 6
Psychiatric disorders
Personality/behavioral 1/498 (0.2%) 1
Renal and urinary disorders
Creatinine 1/498 (0.2%) 1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome (ARDS) 11/498 (2.2%) 11
Apnea 2/498 (0.4%) 2
Dyspnea (shortness of breath) 2/498 (0.4%) 2
Hypoxia 10/498 (2%) 10
Pleural effusion (non-malignant) 4/498 (0.8%) 4
Pneumonitis/pulmonary infiltrates 3/498 (0.6%) 3
Pulmonary-Other 1/498 (0.2%) 1
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other 1/498 (0.2%) 1
Other (Not Including Serious) Adverse Events
Total Therapy
Affected / at Risk (%) # Events
Total 468/498 (94%)
Cardiac disorders
Hypertension 42/498 (8.4%) 42
Hypotension 52/498 (10.4%) 53
Thrombosis/embolism 31/498 (6.2%) 34
Gastrointestinal disorders
Anorexia 26/498 (5.2%) 31
Dehydration 29/498 (5.8%) 36
Diarrhea patients without colostomy 53/498 (10.6%) 62
Stomatitis/pharyngitis (oral/pharyngeal mucositis), 65/498 (13.1%) 75
Typhlitis 27/498 (5.4%) 37
Vomiting 59/498 (11.8%) 67
General disorders
Abdominal pain or cramping 47/498 (9.4%) 69
Fever (in the absence of neutropenia, where neutropenia is defined as AGC<1.0 x 10e9/L) 208/498 (41.8%) 403
Headache 26/498 (5.2%) 38
Hepatobiliary disorders
SGPT (ALT) 76/498 (15.3%) 100
Immune system disorders
Allergic Reaction to Asparaginase 41/498 (8.2%) 45
Infections and infestations
Catheter-related infection 86/498 (17.3%) 131
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe 436/498 (87.6%) 1407
Infection (documented clinically or microbiologically) with grade 3 or 4 neutropenia 379/498 (76.1%) 893
Infection without neutropenia 290/498 (58.2%) 594
Metabolism and nutrition disorders
Hyperglycemia 43/498 (8.6%) 62
Hypokalemia 32/498 (6.4%) 36
Musculoskeletal and connective tissue disorders
Osteonecrosis 35/498 (7%) 60
Nervous system disorders
Neuropathic pain 46/498 (9.2%) 46
Respiratory, thoracic and mediastinal disorders
Hypoxia 51/498 (10.2%) 62
Pleural effusion 25/498 (5%) 25
Pneumonitis/pulmonary infiltrates 29/498 (5.8%) 33
Skin and subcutaneous tissue disorders
Wound-infectious 43/498 (8.6%) 48

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Ching-Hon Pui
Organization St. Jude Children's Research Hospital
Phone 1-866-278-5833
Email info@stjude.org
Responsible Party:
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00137111
Other Study ID Numbers:
  • TOTXV
  • R37CA036401
  • P30CA021765
  • F32CA141762
First Posted:
Aug 29, 2005
Last Update Posted:
Sep 11, 2020
Last Verified:
Sep 1, 2020