Trial · NCT00549848

Total Therapy Study XVI for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia

NCT00549848, Phase 3, Completed, St. Jude Children's Research Hospital; results first posted 2022-02-10

3 sourcestrials-2026-11-12-0.5.0

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ConductScience Library. Total Therapy Study XVI for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia. Trials, record NCT00549848. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT00549848

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Total Therapy Study XVI for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
NCT number: NCT00549848
Status: Completed
Phases: Phase 3
Enrollment: 600 participants, actual
Lead sponsor: St. Jude Children's Research Hospital
Conditions: Acute Lymphoblastic Leukemia
Interventions: Prednisone, Vincristine, Daunorubicin, PEG-L-asparaginase, Erwinia L-asparaginase, Doxorubicin, Cyclophosphamide, Cytarabine, Thioguanine, Clofarabine, Methotrexate, Mercaptopurine, Dexamethasone, Etoposide, Dasatinib
First posted: 2007-10-26
Last updated: 2022-08-23
Results first posted: 2022-02-10

Source ClinicalTrials.gov

Registered outcomes6

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Percentage of Participants With Continuous Complete Remission of Patients Receiving High-dose and Conventional Dose PEG-asparaginase.	3.5 years after the last enrollment up to 12.5 years	The primary objective of this study is to compare the distributions of continuous complete remission of patients randomized on the first day of the continuation phase to receive a higher dose of PEG-asparaginase or to receive the conventional dose (2,500 units/m2). The randomization will occur on the starting day of the continuation phase, at which time all information necessary for performing the randomization should be available. In the rare case that immunophenotype and/or Day-15 MRD is not available, we will make the following assumptions: If immunophenotype is unknown at the time the randomization is to be executed, then it will be assumed B-lineage. If Day-15 MRD is unknown at the time of randomization, then it will be assumed negative (\<0.01%). Past experience indicate that few patients will fall into these unknown categories.
Secondary	Probability of Event-free Survival	For Total XVI: 3.5 years after the last enrollment, up to approximately 13.5 years For Total XV: patients are followed continuously, up to 20.5 years	To estimate the event-free survival of children with ALL who are treated with risk-directed therapy and to compare the EFS results of TOTXVI with that of TOTXV (NCT00137111). EFS will be measured from the date of complete response to the date of initial failure for patients who fail. Failure includes the traditional endpoints of failure to achieve a complete remission, relapse in any site, secondary malignancy, and death during induction or remission. EFS time will be measured to the date of last contact for patients who are failure free at the time of analysis. The EFS time is defined to be zero (0) for patients who die during induction therapy or fail to achieve a complete remission.
Secondary	Probability of Overall Survival	For Total XVI: 3.5 years after the last enrollment, up to approximately 13.5 years For Total XV: patients are followed continuously, up to 20.5 years	To estimate the overall survival of children with ALL who are treated with risk-directed therapy and to compare the EFS results of TOTXVI with that of TOTXV.
Secondary	Proportion of Participants With Minimal Residual Disease (MRD) on the 15th Day of Remission Induction ≥ 5%	Middle of remission induction, Day 15 in Total XVI and Day 19 in Total XV	To study whether intensifying induction, including fractionated cyclophosphamide and thioguanine, in patients with day 15 MRD ≥ 5% will result in improved leukemia cytoreduction in this subgroup compared to therapy followed in the TOTXV protocol.
Secondary	Proportion of Participants With Minimal Residual Disease (MRD) at End of Remission Induction ≥ 0.01%	End of remission induction; day 42 in Total XVI and day 46 in Total XV	To study whether intensifying induction, including fractionated cyclophosphamide and thioguanine, in patients with day 15 MRD ≥ 5% will result in improved leukemia cytoreduction in this subgroup compared to therapy followed in the TOTXV protocol.
Secondary	Probability of CNS Relapse	For Total XVI: 3.5 years after the last enrollment, up to approximately 13.5 years For Total XV: patients are followed continuously, up to 20.5 years	To assess whether intensification of CNS-directed intrathecal and systemic chemotherapy will improve outcome in patients at high-risk of CNS relapse.

Source ClinicalTrials.gov

Outcomes6

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Percentage of Participants With Continuous Complete Remission of Patients Receiving High-dose and Conventional Dose PEG-asparaginase.	3.5 years after the last enrollment up to 12.5 years	Per protocol, the comparison was between the two randomization arms.	Percentage of participants	NUMBER
SECONDARY	Probability of Event-free Survival	For Total XVI: 3.5 years after the last enrollment, up to approximately 13.5 years For Total XV: patients are followed continuously, up to 20.5 years	Per protocol this objective is to study whether intensifying induction will result in improved outcome compared to TOTXV. All eligible patients entered on TOTXVI will be included in these analyses, as appropriate. Infants will be excluded from the Total XVI for comparisons with TOTXV as only children at least one year of age at diagnosis were treated on Total XV.	Percentage of participants	NUMBER
SECONDARY	Probability of Overall Survival	For Total XVI: 3.5 years after the last enrollment, up to approximately 13.5 years For Total XV: patients are followed continuously, up to 20.5 years	All eligible patients entered on TOTXVI will be included in these analyses, as appropriate. Infants will be excluded from the Total XVI for comparisons with TOTXV as only children at least one year of age at diagnosis were treated on Total XV.	Percentage of participants	NUMBER
SECONDARY	Proportion of Participants With Minimal Residual Disease (MRD) on the 15th Day of Remission Induction ≥ 5%	Middle of remission induction, Day 15 in Total XVI and Day 19 in Total XV	The analysis will compare the proportion of TOTXV patients who had Day-19 MRD≥5% with the proportion of patients on TOTXVI with Day-15 MRD≥5%.	Participants	COUNT_OF_PARTICIPANTS
SECONDARY	Proportion of Participants With Minimal Residual Disease (MRD) at End of Remission Induction ≥ 0.01%	End of remission induction; day 42 in Total XVI and day 46 in Total XV	We will compare the proportion of patients with Day-15 MRD≥5% on TOTXVI who are Day-42 MRD positive with the proportion of Day-46 MRD positives in the corresponding subgroup in TOTXV by Fisher's exact test.	Participants	COUNT_OF_PARTICIPANTS
SECONDARY	Probability of CNS Relapse	For Total XVI: 3.5 years after the last enrollment, up to approximately 13.5 years For Total XV: patients are followed continuously, up to 20.5 years	Patients with features associated with increased risk for CNS relapse in Total XVI and Total XV.	Percentage of participants	NUMBER

Source ClinicalTrials.gov

Results by group22

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Value	Spread	Units
Percentage of Participants With Continuous Complete Remission of Patients Receiving High-dose and Conventional Dose PEG-asparaginase.	PEG 3500 Units/m^2	91.6	95% Confidence Interval 87.7 to 95.5	Percentage of participants
Percentage of Participants With Continuous Complete Remission of Patients Receiving High-dose and Conventional Dose PEG-asparaginase.	PEG 2500 Units/m^2	90.7	95% Confidence Interval 86.6 to 94.8	Percentage of participants
Probability of Event-free Survival	TOTXVI PEG 3500	92.4	95% Confidence Interval 88.7 to 96.1	Percentage of participants
Probability of Event-free Survival	TOTXVI PEG 2500	91.1	95% Confidence Interval 87.0 to 95.2	Percentage of participants
Probability of Event-free Survival	TOTXVI Not Randomized	86.3	95% Confidence Interval 78.9 to 93.7	Percentage of participants
Probability of Event-free Survival	All Eligible Patients in TOTXV	87.1	95% Confidence Interval 84.2 to 90.0	Percentage of participants
Probability of Overall Survival	TOTXVI PEG 3500	97.5	95% Confidence Interval 95.3 to 99.7	Percentage of participants
Probability of Overall Survival	TOTXVI PEG 2500	95.6	95% Confidence Interval 92.7 to 98.5	Percentage of participants
Probability of Overall Survival	TOTVI Not Randomized	90.8	95% Confidence Interval 84.7 to 96.9	Percentage of participants
Probability of Overall Survival	All Eligible Patients in TOTXV	93.5	95% Confidence Interval 91.3 to 95.7	Percentage of participants

1 to 10 of 22Source ClinicalTrials.gov

See all 22 results by group

Participant flow9

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	PEG 3500 Units/m^2	206
Overall Study	STARTED	PEG 2500 Units/m^2	208
Overall Study	STARTED	Not Randomized	184
Overall Study	COMPLETED	PEG 3500 Units/m^2	194
Overall Study	COMPLETED	PEG 2500 Units/m^2	188
Overall Study	COMPLETED	Not Randomized	133
Overall Study	NOT COMPLETED	PEG 3500 Units/m^2	12
Overall Study	NOT COMPLETED	PEG 2500 Units/m^2	20
Overall Study	NOT COMPLETED	Not Randomized	51

Source ClinicalTrials.gov

Adverse events174

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	Allergic reaction to Asparaginase	Injury, poisoning and procedural complications	PEG 3500 Units/m^2	28	206	36
other	Allergic reaction to Asparaginase	Injury, poisoning and procedural complications	PEG 2500 Units/m^2	30	208	35
other	Allergic reaction to Asparaginase	Injury, poisoning and procedural complications	Not Randomized	18	184	20
other	Hypertension	Vascular disorders	PEG 3500 Units/m^2	50	206	58
other	Hypertension	Vascular disorders	PEG 2500 Units/m^2	47	208	56
other	Hypertension	Vascular disorders	Not Randomized	58	184	66
other	Hypotension	Vascular disorders	PEG 3500 Units/m^2	16	206	17
other	Hypotension	Vascular disorders	PEG 2500 Units/m^2	19	208	23
other	Hypotension	Vascular disorders	Not Randomized	10	184	13
other	Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	General disorders	PEG 3500 Units/m^2	156	206	395

1 to 10 of 174Source ClinicalTrials.gov

See all 174 adverse events

Adverse event totals9

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	PEG 3500 Units/m^2	9	206
Total, all-cause mortality	PEG 2500 Units/m^2	15	208
Total, all-cause mortality	Not Randomized	22	184
Total, other adverse events	PEG 3500 Units/m^2	206	206
Total, other adverse events	PEG 2500 Units/m^2	208	208
Total, other adverse events	Not Randomized	184	184
Total, serious adverse events	PEG 3500 Units/m^2	0	206
Total, serious adverse events	PEG 2500 Units/m^2	0	208
Total, serious adverse events	Not Randomized	2	184

Source ClinicalTrials.gov

Papers10

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
24970932	DERIVED	PubMed
25087182	DERIVED	PubMed
29020310	DERIVED	PubMed
29518185	DERIVED	PubMed
31188727	DERIVED	PubMed
31612640	DERIVED	PubMed
34170389	DERIVED	PubMed
39121442	DERIVED	PubMed
39316653	DERIVED	PubMed
40908865	DERIVED	PubMed

Grants5

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

Project	Title	Principal investigators	Organization	Funder	Fiscal years	Source
R01CA140729	Drug resistant pathways in relapsed acute lymphoblastic leukemia (ALL)	CARROLL, WILLIAM L.	NEW YORK UNIVERSITY SCHOOL OF MEDICINE	NATIONAL CANCER INSTITUTE	2010 to 2020	NIH RePORTER
P50GM115279	Center for Precision Medicine in Leukemia (CPML)	RELLING, MARY V; LOH, MIGNON LEE-CHEUN	ST. JUDE CHILDREN'S RESEARCH HOSPITAL	NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES	2015 to 2019	NIH RePORTER
R01CA090246	ALL therapy and developing brains: MRI measures, genetic factors and cognition	REDDICK, WILBURN E.	ST. JUDE CHILDREN'S RESEARCH HOSPITAL	NATIONAL CANCER INSTITUTE	2002 to 2015	NIH RePORTER
R37CA036401	PHARMACOGENOMICS OF CHILDHOOD LEUKEMIA (ALL)	EVANS, WILLIAM E	ST. JUDE CHILDREN'S RESEARCH HOSPITAL	NATIONAL CANCER INSTITUTE	1987 to 2014	NIH RePORTER
F32CA141762	MicroRNA pharmacogenomics: implications for childhood leukemia (ALL)	PAUGH, STEVEN WILLIAM	ST. JUDE CHILDREN'S RESEARCH HOSPITAL	NATIONAL CANCER INSTITUTE	2009 to 2011	NIH RePORTER

Trial comparisons0

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

None in this release.

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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