Trial record 67 of 88 for: "Acute Lymphoblastic Leukemia, Childhood" | "Antineoplastic Agents, Hormonal"

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Treatment of Acute Lymphoblastic Leukemia in Children

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ClinicalTrials.gov Identifier: NCT00400946

Recruitment Status : Completed

First Posted : November 17, 2006

Results First Posted : June 14, 2017

Last Update Posted : November 20, 2019

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Lewis B. Silverman, M.D., Dana-Farber Cancer Institute

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Drug/Agent Toxicity by Tissue/Organ Leukemia
Interventions	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: dexamethasone Drug: dexrazoxane hydrochloride Drug: doxorubicin hydrochloride Drug: etoposide Drug: leucovorin calcium Drug: mercaptopurine Drug: methotrexate Drug: methylprednisolone Drug: pegaspargase Drug: prednisolone Drug: therapeutic hydrocortisone Drug: vincristine sulfate Radiation: radiation therapy
Enrollment	800

Participant Flow

Recruitment Details	Patients enrolled from April 22, 2005 to Dec 13, 2011.
Pre-assignment Details


Arm/Group Title	Intramuscular Native E Coli L-asparaginase (IM-EC)	Intravenous PEG-asparaginase (IV-PEG)	IM-EC [Directly Assigned]	Ineligible for Randomization	Expansion Cohort
Arm/Group Description	Patients in this arm were randomize...	Patients in this arm were randomize...	Ph+ ALL patients did not participat...	All patients received a single dose...	Patients were enrolled in an expans...
Arm/Group Description	Patients in this arm were randomized to intramuscular native E coli L-asparaginase 25 000 IU/m2 weekly for 30 doses. Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization. Further details are provided in the study description section.	Patients in this arm were randomized to intravenous PEG-asparaginase 2500 IU/m2 every 2 weeks for 15 doses. Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization. Further details are provided in the study description section.	Ph+ ALL patients did not participate in asparaginase randomization but were directly assigned to receive intramuscular E coli L-asparaginase during post-induction therapy. Patients who were eligible but declined randomization were also directly assigned to receive intramuscular E coli L-asparaginase.	All patients received a single dose of intravenous PEG-asparaginase 2500 IU/m2 during multi-agent induction. Patients who did not achieve complete remission and were not assigned a final risk group by the end of the induction phase of treatment were not eligible for randomization. Patients who developed severe pancreatitis (defined as symptoms persisting for >72 h) during induction were not eligible for randomization and received no further doses of asparaginase. Patients who had hypersensitivity to intravenous PEG-asparaginase during induction were also ineligible for randomization, but received twice-weekly IM-EC (25 000 IU/m2) during the post-induction treatment phases.	Patients were enrolled in an expansion cohort to determine the prognostic significance of response to remission induction chemotherapy as measured by morphologic and minimal residual disease (MRD), and to further evaluate the efficacy of patients by final risk classification.
Period Title: Overall Study
Started	231	232	42	51	244
Evaluable for CNS Directed-Treatment ^[1]	231	232	42	21	227
Evaluable for Day 18 Marrow Morphology ^[2]	158	161	19	13	152
Evaluable for Day 32 MRD ^[3]	166	167	33	12	168
Eligible and Treated ^[4]	231	232	42	46	243
Completed	217	221	40	4	206
Not Completed	14	11	2	47	38
Reason Not Completed
Ineligible	0	0	0	5	1
Induction Failure	0	0	0	11	8
Induction Death	0	0	0	13	3
Lost to Follow-up	1	1	0	0	1
Remission Death	1	1	0	0	1
Relapse	9	2	1	1	5
Transplant in CR1	0	0	0	10	1
Withdrawal by Subject	2	5	1	5	8
Clinical	1	2	0	2	9
Other	0	0	0	0	1
[1] Patients who achieved an induction complete remission with an evaluable sample at diagnosis. [2] Patients who achieved an induction complete remission with an optional evaluable sample at day 18. [3] B cell patients who achieved an induction complete remission with an evaluable sample at day 32. [4] Ineligible: Burkitt's leuk diag (n=2), pr therapy (n=1), hyperbilirubinemia (n=1), w/d consent (n=2)

Baseline Characteristics

Arm/Group Title		Intramuscular Native E Coli L-asparaginase (IM-EC)	Intravenous PEG-asparaginase (IV-PEG)	IM-EC [Directly Assigned]	Ineligible for Randomization	Expansion Cohort	Total
Arm/Group Description		Patients in this arm were randomize...	Patients in this arm were randomize...	Ph+ ALL patients did not participat...	All patients received a single dose...	Patients were enrolled in an expans...	Total of all reporting groups
Arm/Group Description		Patients in this arm were randomized to intramuscular native E coli L-asparaginase 25 000 IU/m2 weekly for 30 doses. Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization. Further details are provided in the study description section.	Patients in this arm were randomized to intravenous PEG-asparaginase 2500 IU/m2 every 2 weeks for 15 doses. Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization. Further details are provided in the study description section.	Ph+ ALL patients did not participate in asparaginase randomization but were directly assigned to receive intramuscular E coli L-asparaginase during post-induction therapy. Patients who were eligible but declined randomization were also directly assigned to receive intramuscular E coli L-asparaginase.	All patients received a single dose of intravenous PEG-asparaginase 2500 IU/m2 during multi-agent induction. Patients who did not achieve complete remission and were not assigned a final risk group by the end of the induction phase of treatment were not eligible for randomization. Patients who developed severe pancreatitis (defined as symptoms persisting for >72 h) during induction were not eligible for randomization and received no further doses of asparaginase. Patients who had hypersensitivity to intravenous PEG-asparaginase during induction were also ineligible for randomization, but received twice-weekly IM-EC (25 000 IU/m2) during the post-induction treatment phases.	Patients were enrolled in an expansion cohort to determine the prognostic significance of response to remission induction chemotherapy as measured by morphologic and minimal residual disease (MRD), and to further evaluate the efficacy of patients by final risk classification.	Total of all reporting groups
Overall Number of Baseline Participants		231	232	42	51	244	800
Baseline Analysis Population Description		...
Baseline Analysis Population Description		The analysis dataset is comprised of all enrolled patients.
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	231 participants	232 participants	42 participants	51 participants	244 participants	800 participants
	<=18 years	231 100.0%	232 100.0%	42 100.0%	51 100.0%	244 100.0%	800 100.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	231 participants	232 participants	42 participants	51 participants	244 participants	800 participants
	Female	111 48.1%	97 41.8%	21 50.0%	21 41.2%	107 43.9%	357 44.6%
	Male	120 51.9%	135 58.2%	21 50.0%	30 58.8%	137 56.1%	443 55.4%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	231 participants	232 participants	42 participants	51 participants	244 participants	800 participants
	Hispanic or Latino	40 17.3%	48 20.7%	3 7.1%	13 25.5%	48 19.7%	152 19.0%
	Not Hispanic or Latino	165 71.4%	170 73.3%	35 83.3%	34 66.7%	180 73.8%	584 73.0%
	Unknown or Not Reported	26 11.3%	14 6.0%	4 9.5%	4 7.8%	16 6.6%	64 8.0%
Age Classification Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	231 participants	232 participants	42 participants	51 participants	244 participants	800 participants
< 10 years old		176 76.2%	165 71.1%	35 83.3%	26 51.0%	196 80.3%	598 74.8%
>/= 10 years old		55 23.8%	67 28.9%	7 16.7%	25 49.0%	48 19.7%	202 25.3%

Outcome Measures

1.Primary Outcome


Title	Asparaginase-Related Toxicity Rate
Description	Asparaginase-related toxicity rate is defined as the percentage of pat...
Description	Asparaginase-related toxicity rate is defined as the percentage of patients who experience allergy (all grades), symptomatic pancreatitis (grade 2 or worse), thrombotic or bleeding complications requiring intervention (grade 2 or worse) with treatment attribution of possibly, probably or definite based on CTCAEv3.
Time Frame	30-week post-induction asparaginase treatment period

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all randomized patients.


Arm/Group Title	Intramuscular Native E Coli L-asparaginase (IM-EC)	Intravenous PEG-asparaginase (IV-PEG)
Arm/Group Description:	Patients in this arm were randomize...	Patients in this arm were randomize...
Arm/Group Description:	Patients in this arm were randomized to intramuscular native E coli L-asparaginase 25 000 IU/m2 weekly for 30 doses. Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization. Further details are provided in the study description section.	Patients in this arm were randomized to intravenous PEG-asparaginase 2500 IU/m2 every 2 weeks for 15 doses. Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization. Further details are provided in the study description section.
Overall Number of Participants Analyzed	231	232
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	26 (20 to 32)	28 (22 to 34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intramuscular Native E Coli L-asparaginase (IM-EC), Intravenous PEG-asparaginase (IV-PEG)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	.60
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

2.Secondary Outcome


Title	5-Year Disease-Free Survival
Description	Disease-free survival (DFS) in a landmark analysis is defined as the d...
Description	Disease-free survival (DFS) in a landmark analysis is defined as the duration of time from asparaginase randomization (which occurred after patients achieved complete remission and were assigned to a final risk group) to documented relapse, death during remission or second malignant neoplasm. DFS is estimated based on the Kaplan-Meier method and 5-year DFS is the probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 5 years from asparaginase randomization. Disease relapse is defined as >25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, FISH, immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the CSF may qualify as CNS leukemia) also qualifies if confirmed by the PI.
Time Frame	Disease evaluations occurred continuously on treatment. Suggested long-term follow-up was monthly for 6m, bi-monthly for 6m, every 4 months for 1y, semi-annually for 1y, then annually. Median follow-up in this study cohort is 6 yrs, up to 10y.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all randomized patients.


Arm/Group Title	Intramuscular Native E Coli L-asparaginase (IM-EC)	Intravenous PEG-asparaginase (IV-PEG)
Arm/Group Description:	Patients in this arm were randomize...	Patients in this arm were randomize...
Arm/Group Description:	Patients in this arm were randomized to intramuscular native E coli L-asparaginase 25 000 IU/m2 weekly for 30 doses. Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization. Further details are provided in the study description section.	Patients in this arm were randomized to intravenous PEG-asparaginase 2500 IU/m2 every 2 weeks for 15 doses. Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization. Further details are provided in the study description section.
Overall Number of Participants Analyzed	231	232
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: probability
	.89 (.85 to .93)	.90 (.86 to .94)

3.Secondary Outcome


Title	Post-Induction Nadir Serum Asparaginase Activity Level
Description	Nadir serum asparaginase activity (NSAA) levels were estimated based o...
Description	Nadir serum asparaginase activity (NSAA) levels were estimated based on established methods.
Time Frame	Samples for nadir serum asparaginase activity analyses were obtained before doses administered at weeks 5, 11, 17, 23 and 29 of post-induction asparaginase treatment.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all randomized patients who consented to research studies with an evaluable sample for analysis of serum asparaginase activity at the respective post-induction assessment timepoints.


Arm/Group Title		Intramuscular Native E Coli L-asparaginase (IM-EC)	Intravenous PEG-asparaginase (IV-PEG)
Arm/Group Description:		Patients in this arm were randomize...	Patients in this arm were randomize...
Arm/Group Description:		Patients in this arm were randomized to intramuscular native E coli L-asparaginase 25 000 IU/m2 weekly for 30 doses. Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization. Further details are provided in the study description section.	Patients in this arm were randomized to intravenous PEG-asparaginase 2500 IU/m2 every 2 weeks for 15 doses. Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization. Further details are provided in the study description section.
Overall Number of Participants Analyzed		231	232
Mean (Standard Deviation) Unit of Measure: IU/mL
Week 5 NSAA Level	Number Analyzed	76 participants	78 participants
Week 5 NSAA Level		0.129 (0.108)	0.726 (0.322)
Week 11 NSAA Level	Number Analyzed	69 participants	76 participants
Week 11 NSAA Level		0.143 (0.131)	0.773 (0.231)
Week 17 NSAA Level	Number Analyzed	85 participants	80 participants
Week 17 NSAA Level		0.159 (0.161)	0.787 (0.303)
Week 23 NSAA Level	Number Analyzed	75 participants	66 participants
Week 23 NSAA Level		0.180 (0.261)	0.757 (0.255)
Week 29 NSAA Level	Number Analyzed	53 participants	69 participants
Week 29 NSAA Level		0.123 (0.102)	0.806 (0.313)

4.Secondary Outcome


Title	Post-Induction Therapeutic Nadir Serum Asparaginase Activity Rate
Description	Nadir serum asparaginase activity (NSAA) levels were estimated based o...
Description	Nadir serum asparaginase activity (NSAA) levels were estimated based on established methods. Post-Induction therapeutic NSAA rate is defined as the percentage of patients achieving a NSAA level above 0.1 IU/mL ever during post-induction therapy.
Time Frame	Samples for nadir serum asparaginase activity analyses were obtained before doses administered at weeks 5, 11, 17, 23 and 29 of post-induction asparaginase treatment.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all randomized patients who consented to research studies with a one post-induction evaluable sample for analysis of serum asparaginase activity.


Arm/Group Title	Intramuscular Native E Coli L-asparaginase (IM-EC)	Intravenous PEG-asparaginase (IV-PEG)
Arm/Group Description:	Patients in this arm were randomize...	Patients in this arm were randomize...
Arm/Group Description:	Patients in this arm were randomized to intramuscular native E coli L-asparaginase 25 000 IU/m2 weekly for 30 doses. Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization. Further details are provided in the study description section.	Patients in this arm were randomized to intravenous PEG-asparaginase 2500 IU/m2 every 2 weeks for 15 doses. Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization. Further details are provided in the study description section.
Overall Number of Participants Analyzed	170	168
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	71 (63 to 77)	99 (96 to 99)

5.Secondary Outcome


Title	Induction Infection Toxicity Rate
Description	Infection toxicity rate is defined as the percentage of patients who e...
Description	Infection toxicity rate is defined as the percentage of patients who experience bacterial or fungal infection of grade 3 or higher with treatment attribution of possibly, probably or definite based on CTCAEv3 during remission induction phase of combination chemotherapy.
Time Frame	Assessed daily during remission induction days 4-32.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of eligible and treated patients. This excludes the 6 enrolled but ineligible patients. Rates in this overall study cohort will be compared against historical controls (in particular patients treated with a more intensive induction regimen).


Arm/Group Title	Overall
Arm/Group Description:	Protocol therapy was comprised of 5...
Arm/Group Description:	Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. All patients received a single dose of intravenous PEG-asparaginase 2500 IU/m2 during multi-agent induction. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization wherein patients received either E. coli L-asparaginase or peg-asparaginase. Standard risk and high-risk patients began post-induction randomized asparaginase therapy at the start of the CNS phase, whereas very high-risk patients began asparaginase therapy on day 8 of consolidation phase IC. Patients who did not achieve complete remission by the end of the induction phase were not eligible for randomization, were removed from protocol treatment, and received alternative therapy according to the discretion of their treating physician. Further details are provided in the study description section.
Overall Number of Participants Analyzed	794
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	26 (23 to 30)

6.Secondary Outcome


Title	Induction Serum Asparaginase Activity Level
Description	Serum asparaginase activity (NSAA) levels were estimated based on esta...
Description	Serum asparaginase activity (NSAA) levels were estimated based on established methods.
Time Frame	Samples for serum asparaginase activity analyses were obtained days 4, 11, 18 and 25 post one-dose of IV-PEG on day 7 of the induction phase.

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Overall
Arm/Group Description:		Protocol therapy was comprised of 5...
Arm/Group Description:		Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. All patients received a single dose of intravenous PEG-asparaginase 2500 IU/m2 during multi-agent induction. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization wherein patients received either E. coli L-asparaginase or peg-asparaginase. Standard risk and high-risk patients began post-induction randomized asparaginase therapy at the start of the CNS phase, whereas very high-risk patients began asparaginase therapy on day 8 of consolidation phase IC. Patients who did not achieve complete remission by the end of the induction phase were not eligible for randomization, were removed from protocol treatment, and received alternative therapy according to the discretion of their treating physician. Further details are provided in the study description section.
Overall Number of Participants Analyzed		794
Median (Inter-Quartile Range) Unit of Measure: IU/mL
Day 4 NSAA Level	Number Analyzed	317 participants
Day 4 NSAA Level		.694 (.556 to .868)
Day 11 NSAA Level	Number Analyzed	348 participants
Day 11 NSAA Level		.505 (.306 to .632)
Day 18 NSAA Level	Number Analyzed	294 participants
Day 18 NSAA Level		.211 (.150 to .259)
Day 25 NSAA Level	Number Analyzed	298 participants
Day 25 NSAA Level		.048 (.025 to .076)

7.Secondary Outcome


Title	Induction Therapeutic Nadir Serum Asparaginase Activity Rate
Description	Nadir serum asparaginase activity (NSAA) levels were estimated based o...
Description	Nadir serum asparaginase activity (NSAA) levels were estimated based on established methods. Induction therapeutic NSAA rate is defined as the percentage of patients achieving a NSAA level above 0.1 IU/mL at a given timepoint.
Time Frame	Samples for serum asparaginase activity analyses were obtained days 4, 11, 18 and 25 post one-dose of IV-PEG on day 7 of the induction phase.

Outcome Measure Data

Analysis Population Description


Arm/Group Title		Overall
Arm/Group Description:		Protocol therapy was comprised of 5...
Arm/Group Description:		Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. All patients received a single dose of intravenous PEG-asparaginase 2500 IU/m2 during multi-agent induction. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization wherein patients received either E. coli L-asparaginase or peg-asparaginase. Standard risk and high-risk patients began post-induction randomized asparaginase therapy at the start of the CNS phase, whereas very high-risk patients began asparaginase therapy on day 8 of consolidation phase IC. Patients who did not achieve complete remission by the end of the induction phase were not eligible for randomization, were removed from protocol treatment, and received alternative therapy according to the discretion of their treating physician. Further details are provided in the study description section.
Overall Number of Participants Analyzed		794
Measure Type: Number Unit of Measure: percentage of participants
Day 4 NSAA Rate	Number Analyzed	317 participants
Day 4 NSAA Rate		97
Day 11 NSAA Rate	Number Analyzed	348 participants
Day 11 NSAA Rate		96
Day 18 NSAA Rate	Number Analyzed	294 participants
Day 18 NSAA Rate		87
Day 25 NSAA Rate	Number Analyzed	298 participants
Day 25 NSAA Rate		12

8.Secondary Outcome


Title	5-Year Disease-Free Survival by MRD Day 32 Status
Description	Disease-free survival (DFS) in a landmark analysis is defined as the d...
Description	Disease-free survival (DFS) in a landmark analysis is defined as the duration of time from asparaginase randomization (which occurred after patients achieved complete remission and were assigned to a final risk group) to documented relapse, death during remission or second malignant neoplasm. DFS is estimated based on the Kaplan-Meier method and 5-year DFS is the probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 5 years from asparaginase randomization. Disease relapse is defined as >25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, FISH, immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the CSF may qualify as CNS leukemia) also qualifies if confirmed by the PI.
Time Frame	Disease evaluations occurred continuously on treatment. Suggested long-term follow-up was monthly for 6m, bi-monthly for 6m, every 4 months for 1y, semi-annually for 1y, then annually. Median follow-up in this study cohort is 6 yrs, up to 10y.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of B cell ALL patients who achieved an induction complete remission with an evaluable sample at day 32 for analysis of MRD.


Arm/Group Title	Low Day 32 MRD Level	High Day 32 MRD Level
Arm/Group Description:	Low end-induction (day 32) minimal ...	High end-induction (day 32) minimal...
Arm/Group Description:	Low end-induction (day 32) minimal residual disease (MRD) evaluated was defined as <0.001. This MRD classification was one component of determining final risk classification. Peripheral blood samples were collected for evaluation of MRD using PCR methods.	High end-induction (day 32) minimal residual disease (MRD) evaluated was defined as >/=0.001. This MRD classification was one component of determining final risk classification. Peripheral blood samples were collected for evaluation of MRD using PCR methods
Overall Number of Participants Analyzed	50	496
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: probability
	.79 (.60 to .86)	.90 (.87 to .93)

9.Secondary Outcome


Title	5-Year Disease-Free Survival by Bone Marrow Day 18 Status
Description	Disease-free survival (DFS) in a landmark analysis is defined as the d...
Description	Disease-free survival (DFS) in a landmark analysis is defined as the duration of time from asparaginase randomization (which occurred after patients achieved complete remission and were assigned to a final risk group) to documented relapse, death during remission or second malignant neoplasm. DFS is estimated based on the Kaplan-Meier method and 5-year DFS is the probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 5 years from asparaginase randomization. Disease relapse is defined as >25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, FISH, immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the CSF may qualify as CNS leukemia) also qualifies if confirmed by the PI.
Time Frame	Disease evaluations occurred continuously on treatment. Suggested long-term follow-up was monthly for 6m, bi-monthly for 6m, every 4 months for 1y, semi-annually for 1y, then annually. Median follow-up in this study cohort is 6 yrs, up to 10y.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of patients who achieved an induction complete remission with an evaluable sample at day 18 (optional submission) for analysis of marrow morphology.


Arm/Group Title	M1 Day 18 Bone Marrow Status	M2/M3 Day 18 Bone Marrow Status	Hypocellular Day 18 Bone Marrow Status
Arm/Group Description:	M1 marrow morphology at day 18 was ...	M2 marrow morphology at day 18 was ...	Hypocellular marrow morphology at d...
Arm/Group Description:	M1 marrow morphology at day 18 was defined as <5% blasts.	M2 marrow morphology at day 18 was defined as 5-24% blasts. M3 marrow morphology at day 18 was defined as >25% blasts.	Hypocellular marrow morphology at day 18 was defined as empty blasts.
Overall Number of Participants Analyzed	284	26	193
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: probability
	.89 (.85 to .92)	.78 (.54 to .90)	.88 (.82 to .92)

10.Secondary Outcome


Title	5-year Disease-Free Survival by CNS Directed Treatment Group
Description	Disease-free survival (DFS) in a landmark analysis is defined as the d...
Description	Disease-free survival (DFS) in a landmark analysis is defined as the duration of time from asparaginase randomization (which occurred after patients achieved complete remission and were assigned to a final risk group) to documented relapse, death during remission or second malignant neoplasm. DFS is estimated based on the Kaplan-Meier method and 5-year DFS is the probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 5 years from asparaginase randomization. Disease relapse is defined as >25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, FISH, immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the CSF may qualify as CNS leukemia) also qualifies if confirmed by the PI.
Time Frame	Disease evaluations occurred continuously on treatment. Suggested long-term follow-up was monthly for 6m, bi-monthly for 6m, every 4 months for 1y, semi-annually for 1y, then annually. Median follow-up in this study cohort is 6 yrs, up to 10y.

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of patients who achieved an induction complete remission with an evaluable sample at diagnosis for analysis of CNS-directed therapy .


Arm/Group Title	CNS-1	CNS-2	CNS-3	Traumatic Tap With Blasts	Traumatic Tap Without Blasts
Arm/Group Description:	CNS-1: no blast cells in cytospin, ...	CNS-2: 5 or fewer WBC on CSF cell c...	CNS-3: more than 5 WBC on CSF cell ...	Traumatic Tap with Blasts: with bla...	Traumatic Tap without Blasts: witho...
Arm/Group Description:	CNS-1: no blast cells in cytospin, regardless of cerebrospinal fluid (CSF) count	CNS-2: 5 or fewer WBC on CSF cell count, with blasts on cytospin	CNS-3: more than 5 WBC on CSF cell count, with blasts on cytospin	Traumatic Tap with Blasts: with blast cells and >100 RBCs on a wet prep	Traumatic Tap without Blasts: without blast cells and >100 RBCs on a wet prep
Overall Number of Participants Analyzed	579	114	9	32	19
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: probability
	.89 (.87 to .92)	.89 (.82 to .94)	1.00 ^[1] (NA to NA)	.84 (.67 to .93)	.87 (.58 to .97)

[1]

NA-not applicable since all patients were disease-free at 5 years.

Adverse Events

Time Frame	Adverse events (AE) were continuously monitored and reported every 3 months during treatment except bony events (avascular necrosis and fracture) which were followed up to 10 years. Treatment duration for this study cohort was a median (range) of 757 days (1-881 days). Data is reported for the entire study cohort (n=794) and comparing randomized arms (n=231/n=232), other non-randomized reporting groups are not reported separately since the intent was not to compare rates between these groups.
Adverse Event Reporting Description	Reporting included (trt-related, all grades [G] unless specified): asparaginase-related allergy, symptomatic pancreatitis (>G1), thrombotic or bleeding complications requiring intervention (>G1), infections (>G2), symptomatic osteonecrosis (>G1), bone fractures and seizures. All other G4-5 AEs were also collected, excl G4 hematological and G4 asymptomatic elevated aminotransferases. Maximum grade toxicity by type was calculated with serious and other AEs defined as G3-5 and G1-2, respectively.

Arm/Group Title	Intramuscular Native E Coli L-asparaginase (IM-EC)	Intravenous PEG-asparaginase (IV-PEG)	Overall
Arm/Group Description	Patients in this arm were randomize...	Patients in this arm were randomize...	Protocol therapy was comprised of 5...
Arm/Group Description	Patients in this arm were randomized to intramuscular native E coli L-asparaginase 25 000 IU/m2 weekly for 30 doses. Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization. Further details are provided in the study description section.	Patients in this arm were randomized to intravenous PEG-asparaginase 2500 IU/m2 every 2 weeks for 15 doses. Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization. Further details are provided in the study description section.	Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, Continuation and varied dependent on risk classification. All patients received a single dose of intravenous PEG-asparaginase 2500 IU/m2 during multi-agent induction. Patients who achieved complete remission after induction were eligible for post-induction asparaginase randomization wherein patients received either E. coli L-asparaginase or peg-asparaginase. Standard risk and high-risk patients began post-induction randomized asparaginase therapy at the start of the CNS phase, whereas very high-risk patients began asparaginase therapy on day 8 of consolidation phase IC. Patients who did not achieve complete remission by the end of the induction phase were not eligible for randomization, were removed from protocol treatment, and received alternative therapy according to the discretion of their treating physician. Further details are provided in the study description section.
All-Cause Mortality
	Intramuscular Native E Coli L-asparaginase (IM-EC)	Intravenous PEG-asparaginase (IV-PEG)	Overall
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/231 (0.43%)	1/232 (0.43%)	2/794 (0.25%)
Serious Adverse Events Serious Adverse Events
	Intramuscular Native E Coli L-asparaginase (IM-EC)	Intravenous PEG-asparaginase (IV-PEG)	Overall
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	132/231 (57.14%)	142/232 (61.21%)	574/794 (72.29%)
Blood and lymphatic system disorders
Hematologic-other ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Hemolysis ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Hemoglobin ^† 1	4/231 (1.73%)	0/232 (0.00%)	12/794 (1.51%)
Febrile neutropenia ^† 1	6/231 (2.60%)	7/232 (3.02%)	18/794 (2.27%)
Cardiac disorders
Atrial flutter ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Cardiac-other ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Left ventricular systolic dysfunction ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Sinus tachycardia ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Ventricular tachycardia ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Gastrointestinal disorders
Cecum/appendix- hemorrhage ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Enteritis ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Nausea ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Necrosis- pancreas ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Oral cavity- pain ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Perforation- stomach ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Ulcer- anus ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Ulcer- duodenum ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Ulcer- esophagus ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Ulcer- gastric ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Varices (esophageal)- hemorrhage ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Colitis ^† 1	1/231 (0.43%)	0/232 (0.00%)	2/794 (0.25%)
Duodenum- hemorrhage ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Esophagitis ^† 1	1/231 (0.43%)	0/232 (0.00%)	2/794 (0.25%)
Lower GI- hemorrhage NOS ^† 1	0/231 (0.00%)	1/232 (0.43%)	2/794 (0.25%)
Oral gums- pain ^† 1	1/231 (0.43%)	1/232 (0.43%)	2/794 (0.25%)
Perforation- small bowel NOS ^† 1	0/231 (0.00%)	1/232 (0.43%)	2/794 (0.25%)
Vomiting ^† 1	1/231 (0.43%)	0/232 (0.00%)	2/794 (0.25%)
Constipation ^† 1	1/231 (0.43%)	0/232 (0.00%)	3/794 (0.38%)
Diarrhea w/o prior colostomy ^† 1	1/231 (0.43%)	0/232 (0.00%)	3/794 (0.38%)
Upper GI- hemorrhage NOS ^† 1	0/231 (0.00%)	0/232 (0.00%)	3/794 (0.38%)
Abdomen- pain ^† 1	0/231 (0.00%)	2/232 (0.86%)	4/794 (0.50%)
Ileus ^† 1	0/231 (0.00%)	0/232 (0.00%)	4/794 (0.50%)
Muco/stomatitis (symptom) oral cavity ^† 1	2/231 (0.87%)	2/232 (0.86%)	7/794 (0.88%)
Typhlitis ^† 1	0/231 (0.00%)	2/232 (0.86%)	16/794 (2.02%)
Pancreatitis ^† 1	3/231 (1.30%)	9/232 (3.88%)	26/794 (3.27%)
Muco/stomatitis by exam- oral cavity ^† 1	15/231 (6.49%)	21/232 (9.05%)	100/794 (12.59%)
General disorders
Death - multiorgan failure ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Death - sudden death ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Edema limb ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Pain NOS ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Fatigue ^† 1	1/231 (0.43%)	1/232 (0.43%)	2/794 (0.25%)
Fever w/o neutropenia ^† 1	0/231 (0.00%)	1/232 (0.43%)	2/794 (0.25%)
Pain-other ^† 1	1/231 (0.43%)	0/232 (0.00%)	2/794 (0.25%)
Extremity-lower (gait/walking) ^† 1	1/231 (0.43%)	1/232 (0.43%)	6/794 (0.76%)
Hepatobiliary disorders
Liver dysfunction/failure ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Immune system disorders
Allergic reaction ^† 1	6/231 (2.60%)	14/232 (6.03%)	33/794 (4.16%)
Infections and infestations
Infection Gr0-2 neut- bladder ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Infection Gr0-2 neut- bronchus ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection Gr0-2 neut- cervix ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Infection Gr0-2 neut- dental-tooth ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection Gr0-2 neut- middle ear ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Infection Gr0-2 neut- muscle ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Infection Gr0-2 neut- soft tissue ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Infection Gr0-2 neut- spleen ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- brain ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Infection w/ gr3-4 neut- brain + spinal ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- dental-tooth ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- eye NOS ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- lens ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- lip/perioral ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Infection w/ gr3-4 neut- liver ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Infection w/ gr3-4 neut- paranasal ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Infection w/ gr3-4 neut- pleura ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- sinus ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- spinal cord ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- spleen ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Infection w/ gr3-4 neut- trachea ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- vein ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ unk ANC abdomen NOS ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ unk ANC colon ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ unk ANC lymphatic ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ unk ANC meninges ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ unk ANC skin (cellulitis) ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ unk ANC ungual (nails) ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ unk ANC upper airway NOS ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ unk ANC urinary tract NOS ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection Gr0-2 neut- abdomen ^† 1	0/231 (0.00%)	1/232 (0.43%)	2/794 (0.25%)
Infection Gr0-2 neut- catheter ^† 1	0/231 (0.00%)	1/232 (0.43%)	2/794 (0.25%)
Infection Gr0-2 neut- eye NOS ^† 1	0/231 (0.00%)	1/232 (0.43%)	2/794 (0.25%)
Infection Gr0-2 neut- liver ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Infection Gr0-2 neut- peritoneal ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Infection Gr0-2 neut- wound ^† 1	2/231 (0.87%)	0/232 (0.00%)	2/794 (0.25%)
Infection w/ gr3-4 neut- anal/perianal ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Infection w/ gr3-4 neut- kidney ^† 1	0/231 (0.00%)	1/232 (0.43%)	2/794 (0.25%)
Infection w/ gr3-4 neut- meninges ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Infection w/ gr3-4 neut- middle ear ^† 1	1/231 (0.43%)	0/232 (0.00%)	2/794 (0.25%)
Infection w/ gr3-4 neut- peritoneal ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Infection w/ gr3-4 neut- urinary tract ^† 1	1/231 (0.43%)	0/232 (0.00%)	2/794 (0.25%)
Infection w/ unk ANC bladder ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Infection w/ unk ANC lung ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Infection w/ unk ANC wound ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Infection Gr0-2 neut- urinary tract ^† 1	2/231 (0.87%)	0/232 (0.00%)	4/794 (0.50%)
Infection w/ gr3-4 neut- catheter relate ^† 1	0/231 (0.00%)	0/232 (0.00%)	4/794 (0.50%)
Infection w/ gr3-4 neut- upper airway ^† 1	2/231 (0.87%)	1/232 (0.43%)	4/794 (0.50%)
Infection w/ gr3-4 neut- wound ^† 1	0/231 (0.00%)	1/232 (0.43%)	4/794 (0.50%)
Infection w/ gr3-4 neut- lung ^† 1	0/231 (0.00%)	1/232 (0.43%)	7/794 (0.88%)
Infection Gr0-2 neut- skin ^† 1	3/231 (1.30%)	2/232 (0.86%)	8/794 (1.01%)
Infection-other ^† 1	1/231 (0.43%)	3/232 (1.29%)	9/794 (1.13%)
Infection Gr0-2 neut- lung ^† 1	5/231 (2.16%)	2/232 (0.86%)	10/794 (1.26%)
Infection w/ gr3-4 neut- skin ^† 1	6/231 (2.60%)	1/232 (0.43%)	12/794 (1.51%)
Colitis- infectious (e.g. C.diff) ^† 1	1/231 (0.43%)	2/232 (0.86%)	13/794 (1.64%)
Opportunistic infection lymphopenia>=gr1 ^† 1	5/231 (2.16%)	6/232 (2.59%)	15/794 (1.89%)
Infection Gr 0-2 neut- blood ^† 1	33/231 (14.29%)	30/232 (12.93%)	103/794 (12.97%)
Infection w/ gr 3-4 neut- blood ^† 1	25/231 (10.82%)	29/232 (12.50%)	234/794 (29.47%)
Injury, poisoning and procedural complications
Intra-op injury Other (Specify) ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Intra-op injury Pleura ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Surgical hemorrhage ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Wound - non-infectious ^† 1	0/231 (0.00%)	1/232 (0.43%)	2/794 (0.25%)
Fracture ^† 1	5/231 (2.16%)	1/232 (0.43%)	11/794 (1.39%)
Investigations
ADH secretion abnormality (eg SIADH) ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Alkaline phosphatase ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Coagulation-other ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Creatinine ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
INR ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
PTT ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Hypercholesterolemia ^† 1	0/231 (0.00%)	1/232 (0.43%)	2/794 (0.25%)
Fibrinogen ^† 1	0/231 (0.00%)	0/232 (0.00%)	3/794 (0.38%)
Leukocytes ^† 1	0/231 (0.00%)	0/232 (0.00%)	3/794 (0.38%)
Metabolic/Laboratory-other ^† 1	0/231 (0.00%)	1/232 (0.43%)	4/794 (0.50%)
Neutrophils ^† 1	1/231 (0.43%)	2/232 (0.86%)	6/794 (0.76%)
Platelets ^† 1	1/231 (0.43%)	0/232 (0.00%)	6/794 (0.76%)
GGT ^† 1	1/231 (0.43%)	1/232 (0.43%)	7/794 (0.88%)
Bilirubin ^† 1	1/231 (0.43%)	4/232 (1.72%)	16/794 (2.02%)
AST- SGOT ^† 1	4/231 (1.73%)	8/232 (3.45%)	28/794 (3.53%)
Amylase ^† 1	5/231 (2.16%)	6/232 (2.59%)	37/794 (4.66%)
ALT- SGPT ^† 1	9/231 (3.90%)	10/232 (4.31%)	48/794 (6.05%)
Lipase ^† 1	12/231 (5.19%)	10/232 (4.31%)	49/794 (6.17%)
Metabolism and nutrition disorders
Hypoalbuminemia ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Iron overload ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Urinary electrolyte wasting ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Hyperkalemia ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Hyperuricemia ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Anorexia ^† 1	2/231 (0.87%)	0/232 (0.00%)	4/794 (0.50%)
Dehydration ^† 1	1/231 (0.43%)	0/232 (0.00%)	4/794 (0.50%)
Hypophosphatemia ^† 1	1/231 (0.43%)	1/232 (0.43%)	4/794 (0.50%)
Tumor lysis syndrome ^† 1	0/231 (0.00%)	0/232 (0.00%)	4/794 (0.50%)
Hypocalcemia ^† 1	0/231 (0.00%)	0/232 (0.00%)	7/794 (0.88%)
Hypoglycemia ^† 1	4/231 (1.73%)	1/232 (0.43%)	7/794 (0.88%)
Hyponatremia ^† 1	1/231 (0.43%)	2/232 (0.86%)	11/794 (1.39%)
Hypokalemia ^† 1	8/231 (3.46%)	5/232 (2.16%)	22/794 (2.77%)
Hyperglycemia ^† 1	6/231 (2.60%)	1/232 (0.43%)	25/794 (3.15%)
Hypertriglyceridemia ^† 1	12/231 (5.19%)	20/232 (8.62%)	69/794 (8.69%)
Musculoskeletal and connective tissue disorders
Back- pain ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Joint- pain ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Muscular/skeletal hypoplasia ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Nonneuropathic lower extr muscle weak ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Osteoporosis ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Soft tissue necrosis- extremity lower ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Bone- pain ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Extremity-limb- pain ^† 1	1/231 (0.43%)	1/232 (0.43%)	5/794 (0.63%)
Osteonecrosis (avascular necrosis) ^† 1	6/231 (2.60%)	6/232 (2.59%)	15/794 (1.89%)
Nervous system disorders
CNS cerebrovascular ischemia ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Head/headache ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Speech impairment ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Syncope ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Myelitis ^† 1	0/231 (0.00%)	1/232 (0.43%)	3/794 (0.38%)
Neurologic-other ^† 1	1/231 (0.43%)	1/232 (0.43%)	3/794 (0.38%)
Neuropathy-sensory ^† 1	2/231 (0.87%)	0/232 (0.00%)	4/794 (0.50%)
CNS- hemorrhage ^† 1	2/231 (0.87%)	1/232 (0.43%)	6/794 (0.76%)
Encephalopathy ^† 1	2/231 (0.87%)	0/232 (0.00%)	6/794 (0.76%)
Neuropathy-motor ^† 1	2/231 (0.87%)	3/232 (1.29%)	14/794 (1.76%)
Seizure ^† 1	6/231 (2.60%)	6/232 (2.59%)	22/794 (2.77%)
Psychiatric disorders
Anxiety ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Insomnia ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Personality ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Agitation ^† 1	0/231 (0.00%)	2/232 (0.86%)	2/794 (0.25%)
Confusion ^† 1	1/231 (0.43%)	0/232 (0.00%)	2/794 (0.25%)
Depression ^† 1	1/231 (0.43%)	1/232 (0.43%)	3/794 (0.38%)
Psychosis ^† 1	0/231 (0.00%)	1/232 (0.43%)	3/794 (0.38%)
Renal and urinary disorders
Kidney- pain ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Obstruction-ureteral ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Perforation- appendix ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Renal failure ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Reproductive system and breast disorders
Pelvic- pain ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary- hemorrhage ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Cough ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Lung- hemorrhage ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
(ARDS) ^† 1	1/231 (0.43%)	0/232 (0.00%)	2/794 (0.25%)
Dyspnea ^† 1	1/231 (0.43%)	0/232 (0.00%)	2/794 (0.25%)
Pleural effusion (non-malignant) ^† 1	0/231 (0.00%)	1/232 (0.43%)	2/794 (0.25%)
Pulmonary/Upper Respiratory-other ^† 1	0/231 (0.00%)	1/232 (0.43%)	3/794 (0.38%)
Hypoxia ^† 1	0/231 (0.00%)	0/232 (0.00%)	6/794 (0.76%)
Pneumonitis/pulmonary infiltrates ^† 1	3/231 (1.30%)	1/232 (0.43%)	9/794 (1.13%)
Skin and subcutaneous tissue disorders
Pruritus/itching ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Skin breakdown/decubitus ulcer ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Skin-other ^† 1	1/231 (0.43%)	0/232 (0.00%)	3/794 (0.38%)
Vascular disorders
Acute vascular leak syndrome ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Chyle or lymph leakage ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Peripheral arterial ischemia ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Hypotension ^† 1	2/231 (0.87%)	3/232 (1.29%)	10/794 (1.26%)
Vascular access-Thrombosis/embolism ^† 1	8/231 (3.46%)	2/232 (0.86%)	15/794 (1.89%)
Hypertension ^† 1	2/231 (0.87%)	3/232 (1.29%)	39/794 (4.91%)
Thrombosis/thrombus/embolism ^† 1	10/231 (4.33%)	12/232 (5.17%)	55/794 (6.93%)
1 Term from vocabulary, CTCAE (3.0) † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Intramuscular Native E Coli L-asparaginase (IM-EC)	Intravenous PEG-asparaginase (IV-PEG)	Overall
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	40/231 (17.32%)	38/232 (16.38%)	118/794 (14.86%)
Blood and lymphatic system disorders
Hemoglobin ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Febrile neutropenia ^† 1	3/231 (1.30%)	2/232 (0.86%)	7/794 (0.88%)
Cardiac disorders
Sinus tachycardia ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Left ventricular systolic dysfunction ^† 1	0/231 (0.00%)	0/232 (0.00%)	3/794 (0.38%)
Ear and labyrinth disorders
Otitis- middle ear (non-infectious) ^† 1	0/231 (0.00%)	3/232 (1.29%)	3/794 (0.38%)
Gastrointestinal disorders
Enteritis ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Muco/stomatitis (symptom) anus ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Oral cavity- pain ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Perforation- stomach ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Diarrhea w/o prior colostomy ^† 1	0/231 (0.00%)	1/232 (0.43%)	2/794 (0.25%)
Ulcer- anus ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Colitis ^† 1	0/231 (0.00%)	1/232 (0.43%)	4/794 (0.50%)
Constipation ^† 1	0/231 (0.00%)	0/232 (0.00%)	4/794 (0.50%)
Typhlitis ^† 1	0/231 (0.00%)	0/232 (0.00%)	4/794 (0.50%)
Muco/stomatitis (symptom) oral cavity ^† 1	0/231 (0.00%)	1/232 (0.43%)	5/794 (0.63%)
Muco/stomatitis by exam- oral cavity ^† 1	7/231 (3.03%)	7/232 (3.02%)	31/794 (3.90%)
Pancreatitis ^† 1	15/231 (6.49%)	17/232 (7.33%)	61/794 (7.68%)
General disorders
Chest/thoracic pain NOS ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Extremity-lower (gait/walking) ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Fatigue ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Hypothermia ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Fever w/o neutropenia ^† 1	1/231 (0.43%)	4/232 (1.72%)	5/794 (0.63%)
Pain-other ^† 1	1/231 (0.43%)	1/232 (0.43%)	5/794 (0.63%)
Immune system disorders
Allergy-other ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Allergic reaction ^† 1	8/231 (3.46%)	13/232 (5.60%)	33/794 (4.16%)
Infections and infestations
Infection Gr0-2 neut- bladder ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Infection Gr0-2 neut- bronchus ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Infection Gr0-2 neut- external ear ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection Gr0-2 neut- eye NOS ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection Gr0-2 neut- kidney ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Infection Gr0-2 neut- lung ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Infection Gr0-2 neut- lymphatic ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Infection Gr0-2 neut- meninges ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- bronchus ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Infection w/ gr3-4 neut- catheter relate ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- eye NOS ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Infection w/ gr3-4 neut- larynx ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- middle ear ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- peritoneal ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- pharynx ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- urinary tract ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ gr3-4 neut- wound ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Infection w/ unk ANC catheter related ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ unk ANC skin (cellulitis) ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ unk ANC ungual (nails) ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ unk ANC upper airway NOS ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection w/ unk ANC wound ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Infection Gr0-2 neut- conjunctiva ^† 1	1/231 (0.43%)	1/232 (0.43%)	2/794 (0.25%)
Infection Gr0-2 neut- middle ear ^† 1	1/231 (0.43%)	1/232 (0.43%)	2/794 (0.25%)
Infection Gr0-2 neut- mucosa ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Infection Gr0-2 neut- ungual ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Infection Gr0-2 neut- upper airway ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Infection Gr0-2 neut- wound ^† 1	1/231 (0.43%)	0/232 (0.00%)	2/794 (0.25%)
Infection w/ unk ANC lung ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Infection w/ unk ANC urinary tract NOS ^† 1	0/231 (0.00%)	1/232 (0.43%)	2/794 (0.25%)
Infection Gr0-2 neut- nose ^† 1	2/231 (0.87%)	0/232 (0.00%)	3/794 (0.38%)
Infection Gr0-2 neut- sinus ^† 1	0/231 (0.00%)	1/232 (0.43%)	3/794 (0.38%)
Infection Gr0-2 neut- skin ^† 1	1/231 (0.43%)	1/232 (0.43%)	3/794 (0.38%)
Infection Gr0-2 neut- urinary tract ^† 1	0/231 (0.00%)	1/232 (0.43%)	3/794 (0.38%)
Infection w/ gr 3-4 neut- blood ^† 1	0/231 (0.00%)	1/232 (0.43%)	3/794 (0.38%)
Infection Gr0-2 neut- oral cavity ^† 1	0/231 (0.00%)	2/232 (0.86%)	4/794 (0.50%)
Infection-other ^† 1	2/231 (0.87%)	0/232 (0.00%)	4/794 (0.50%)
Colitis- infectious (e.g. C.diff) ^† 1	1/231 (0.43%)	1/232 (0.43%)	6/794 (0.76%)
Opportunistic infection lymphopenia>=gr1 ^† 1	5/231 (2.16%)	1/232 (0.43%)	10/794 (1.26%)
Infection Gr 0-2 neut- blood ^† 1	12/231 (5.19%)	9/232 (3.88%)	32/794 (4.03%)
Injury, poisoning and procedural complications
Chemoradiation dermatitis ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Fracture ^† 1	37/231 (16.02%)	38/232 (16.38%)	118/794 (14.86%)
Investigations
Creatinine ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Lipase ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Neutrophils ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Weight loss ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
ALT- SGPT ^† 1	1/231 (0.43%)	0/232 (0.00%)	4/794 (0.50%)
Amylase ^† 1	1/231 (0.43%)	2/232 (0.86%)	4/794 (0.50%)
AST- SGOT ^† 1	2/231 (0.87%)	0/232 (0.00%)	6/794 (0.76%)
Metabolism and nutrition disorders
Dehydration ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Hypoglycemia ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Hyperglycemia ^† 1	0/231 (0.00%)	0/232 (0.00%)	2/794 (0.25%)
Hypertriglyceridemia ^† 1	3/231 (1.30%)	7/232 (3.02%)	14/794 (1.76%)
Musculoskeletal and connective tissue disorders
Muscle- pain ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Musculoskeletal/soft tissue-other ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Nonneuropathic lower extr muscle weak ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Back- pain ^† 1	0/231 (0.00%)	1/232 (0.43%)	2/794 (0.25%)
Joint- pain ^† 1	1/231 (0.43%)	0/232 (0.00%)	2/794 (0.25%)
Bone- pain ^† 1	1/231 (0.43%)	0/232 (0.00%)	3/794 (0.38%)
Extremity-limb- pain ^† 1	2/231 (0.87%)	1/232 (0.43%)	4/794 (0.50%)
Osteonecrosis (avascular necrosis) ^† 1	15/231 (6.49%)	15/232 (6.47%)	45/794 (5.67%)
Nervous system disorders
Neurologic-other ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Speech impairment ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Syncope ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
CNS- hemorrhage ^† 1	4/231 (1.73%)	0/232 (0.00%)	4/794 (0.50%)
Neuropathy-sensory ^† 1	1/231 (0.43%)	0/232 (0.00%)	4/794 (0.50%)
Neuropathy-motor ^† 1	0/231 (0.00%)	0/232 (0.00%)	5/794 (0.63%)
Seizure ^† 1	5/231 (2.16%)	5/232 (2.16%)	17/794 (2.14%)
Psychiatric disorders
Agitation ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Psychosis ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Personality ^† 1	1/231 (0.43%)	0/232 (0.00%)	2/794 (0.25%)
Respiratory, thoracic and mediastinal disorders
Atelectasis ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Cough ^† 1	1/231 (0.43%)	0/232 (0.00%)	1/794 (0.13%)
Hypoxia ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Pulmonary/Upper Respiratory-other ^† 1	0/231 (0.00%)	1/232 (0.43%)	1/794 (0.13%)
Pneumonitis/pulmonary infiltrates ^† 1	0/231 (0.00%)	2/232 (0.86%)	2/794 (0.25%)
Skin and subcutaneous tissue disorders
Erythema multiforme ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Ulceration ^† 1	0/231 (0.00%)	0/232 (0.00%)	1/794 (0.13%)
Skin-other ^† 1	2/231 (0.87%)	3/232 (1.29%)	5/794 (0.63%)
Vascular disorders
Hypotension ^† 1	1/231 (0.43%)	1/232 (0.43%)	2/794 (0.25%)
Vascular access-Thrombosis/embolism ^† 1	1/231 (0.43%)	3/232 (1.29%)	6/794 (0.76%)
Thrombosis/thrombus/embolism ^† 1	9/231 (3.90%)	4/232 (1.72%)	22/794 (2.77%)
Hypertension ^† 1	8/231 (3.46%)	4/232 (1.72%)	58/794 (7.30%)
1 Term from vocabulary, CTCAE (3.0) † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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

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Name/Title:	Lewis B. Silverman, MD
Organization:	Dana-Farber Cancer Institute
Phone:	617.632.6191
EMail:	Lewis_Silverman@dfci.harvard.edu

Publications of Results:

Silverman LB, Supko JG, Stevenson KE, Woodward C, Vrooman LM, Neuberg DS, Asselin BL, Athale UH, Clavell L, Cole PD, Kelly KM, Laverdière C, Michon B, Schorin M, Schwartz CL, O'Brien JE, Cohen HJ, Sallan SE. Intravenous PEG-asparaginase during remission induction in children and adolescents with newly diagnosed acute lymphoblastic leukemia. Blood. 2010 Feb 18;115(7):1351-3. doi: 10.1182/blood-2009-09-245951. Epub 2009 Dec 10.

Place AE, Stevenson KE, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Supko JG, Asselin BL, Athale UH, Clavell LA, Cole PD, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Welch JJ, Lipshultz SE, Kutok JL, Blonquist TM, Neuberg DS, Sallan SE, Silverman LB. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1677-90. doi: 10.1016/S1470-2045(15)00363-0. Epub 2015 Nov 6.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vrooman LM, Blonquist TM, Harris MH, Stevenson KE, Place AE, Hunt SK, O'Brien JE, Asselin BL, Athale UH, Clavell LA, Cole PD, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Sulis ML, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Refining risk classification in childhood B acute lymphoblastic leukemia: results of DFCI ALL Consortium Protocol 05-001. Blood Adv. 2018 Jun 26;2(12):1449-1458. doi: 10.1182/bloodadvances.2018016584.

Kahn JM, Cole PD, Blonquist TM, Stevenson K, Jin Z, Barrera S, Davila R, Roberts E, Neuberg DS, Athale UH, Clavell LA, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Welch JJG, Sallan SE, Silverman LB, Kelly KM. An investigation of toxicities and survival in Hispanic children and adolescents with ALL: Results from the Dana-Farber Cancer Institute ALL Consortium protocol 05-001. Pediatr Blood Cancer. 2018 Mar;65(3). doi: 10.1002/pbc.26871. Epub 2017 Nov 1.

Layout table for additonal information

Responsible Party:	Lewis B. Silverman, M.D., Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00400946 History of Changes
Obsolete Identifiers:	NCT00165165
Other Study ID Numbers:	05-001 / CDR0000513019 P01CA068484 ( U.S. NIH Grant/Contract ) P30CA006516 ( U.S. NIH Grant/Contract ) DFCI-05001 ( Other Identifier: DFCI IRB Protocol Number )
First Submitted:	November 16, 2006
First Posted:	November 17, 2006
Results First Submitted:	January 17, 2017
Results First Posted:	June 14, 2017
Last Update Posted:	November 20, 2019

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