Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents
NCT ID: NCT03020030
Last Updated: 2026-01-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE3
560 participants
INTERVENTIONAL
2017-03-03
2034-11-30
Brief Summary
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The standard treatment for ALL involves about 2 years of chemotherapy. The drugs that are used, and the doses of the drugs, are similar but not identical for all children and adolescents with ALL. Some children and adolescents receive stronger treatment, especially during the first several months. A number of factors are used to decide how strong the treatment should be to give the best chance for cure. These factors are called "risk factors". This trial is studying the use of a new, updated set of risk factors to decide how strong the treatment will be. The study also will test a new way of dosing a chemotherapy drug called pegaspargase (which is part of the standard treatment for ALL) based on checking levels of the drug in the blood and adjusting the dose based on the levels.
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Detailed Description
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Over the last several years, new factors have been identified which help predict how well a child's leukemia may respond to treatment. These new risk factors include additional abnormalities in the genes of the leukemia cell, as well the amount of leukemia (MRD level) at second time point (about 2-3 months after starting treatment).
In this trial, the investigators will use the new risk factors along with old risk factors to decide how strong the treatment will be. The goal is to better identify those participants who might benefit from stronger treatment in order to improve their chance for cure. The investigators also hope to better identify participants who have a high chance of being cured with standard treatment in order to reduce their chance of side effects while maintaining the chance of cure.
This trial also aims to study the dosing of a drug called pegaspargase. Pegaspargase is a chemotherapy drug that is an important part of ALL treatment but it is also can cause many side effects. With the standard dose of pegaspargase, levels of the drug in the blood are higher than may be necessary to effectively treat leukemia.
On this research study, the investigators will be comparing the standard dose of pegaspargase with a new way of dosing the drug based on levels of the drug that we can measure in the blood. With the new way of doing, treatment will begin with a lower dose. If the levels are high, the dose will be decreased one more time; however, if at any time the levels are too low, dosing will be switched back up to the standard dose. The goal of this research study is to learn whether this new way of dosing (starting at a lower dose and changing the dose based on drug levels in the blood) will decrease side effects but still be as effective as the standard dosing of the drug.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Initial Low Risk (Initial LR)
Meets all the following criteria: B-ALL, Age 1-\<15 years, WBC \< 50,000/microliter, CNS-1 or CNS-2, no BCR-ABL1, no iAMP21, and no VHR characteristics.
Treated with Induction IA (vincristine, dexamethasone, pegaspargase), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.
Pegaspargase
Arm A: Standard/Fixed Dose Pegaspargase (2500 IU/m2 every 2 weeks) Arm B: Reduced Dose (PK-adjusted) Pegaspargase (Starting Dose: 2000 IU/m2) Arm X: Directly Assigned Standard Dose (2500 IU/m2): For all VHR and patients who decline randomization
Erwinia asparaginase
Only for patients with Pegaspargase allergy or silent inactivation.
Cyclophosphamide
Standard of Care
CYTARABINE
Standard of Care
DEXAMETHASONE
Standard of Care
HYDROCORTISONE
Standard of Care
LEUCOVORIN CALCIUM
Standard of Care
MERCAPTOPURINE
Standard of Care
METHOTREXATE
Standard of Care
Vincristine
Standard of Care
Initial High Risk (Initial HR)
Meets at least one of the following criteria: Age \>=15 years, WBC \>=50,000/microliter, CNS-3, T-ALL, iAMP21, BCR-ABL1
And: No VHR characteristics
Treated with Induction IA (vincristine, dexamethasone, pegaspargase, doxorubicin + dexrazoxane), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.
Pegaspargase
Arm A: Standard/Fixed Dose Pegaspargase (2500 IU/m2 every 2 weeks) Arm B: Reduced Dose (PK-adjusted) Pegaspargase (Starting Dose: 2000 IU/m2) Arm X: Directly Assigned Standard Dose (2500 IU/m2): For all VHR and patients who decline randomization
Erwinia asparaginase
Only for patients with Pegaspargase allergy or silent inactivation.
Cyclophosphamide
Standard of Care
CYTARABINE
Standard of Care
DEXAMETHASONE
Standard of Care
Dexrazoxane
Standard of Care
Doxorubicin
Standard of Care
HYDROCORTISONE
Standard of Care
LEUCOVORIN CALCIUM
Standard of Care
MERCAPTOPURINE
Standard of Care
METHOTREXATE
Standard of Care
Vincristine
Standard of Care
Initial Very High Risk (Initial VHR)
Any of the following are present: IKZF1 deletion, MLL (KMT2A) rearrangement, low hypodiploidy, t(17;19)
Treated with Induction IA (vincristine, dexamethasone, pegaspargase, doxorubicin + dexrazoxane), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.
Pegaspargase
Arm A: Standard/Fixed Dose Pegaspargase (2500 IU/m2 every 2 weeks) Arm B: Reduced Dose (PK-adjusted) Pegaspargase (Starting Dose: 2000 IU/m2) Arm X: Directly Assigned Standard Dose (2500 IU/m2): For all VHR and patients who decline randomization
Erwinia asparaginase
Only for patients with Pegaspargase allergy or silent inactivation.
Cyclophosphamide
Standard of Care
CYTARABINE
Standard of Care
DASATINIB
Standard of Care
DEXAMETHASONE
Standard of Care
Dexrazoxane
Standard of Care
Doxorubicin
Standard of Care
ETOPOSIDE
Standard of Care
HYDROCORTISONE
Standard of Care
LEUCOVORIN CALCIUM
Standard of Care
MERCAPTOPURINE
Standard of Care
METHOTREXATE
Standard of Care
NELARABINE
Standard of Care
Vincristine
Standard of Care
Final Low Risk (Final LR)
Initial Low Risk and Low MRD (\<0.0001) at first time point (Day 32)
Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:
CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase \[by randomization or direct assignment\], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, methotrexate, pegaspargase \[by randomization or direct assignment\], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).
All treatment completed 24 months from date of complete remission.
Pegaspargase
Arm A: Standard/Fixed Dose Pegaspargase (2500 IU/m2 every 2 weeks) Arm B: Reduced Dose (PK-adjusted) Pegaspargase (Starting Dose: 2000 IU/m2) Arm X: Directly Assigned Standard Dose (2500 IU/m2): For all VHR and patients who decline randomization
Erwinia asparaginase
Only for patients with Pegaspargase allergy or silent inactivation.
CYTARABINE
Standard of Care
DEXAMETHASONE
Standard of Care
HYDROCORTISONE
Standard of Care
MERCAPTOPURINE
Standard of Care
METHOTREXATE
Standard of Care
Vincristine
Standard of Care
Final Intermediate Risk (Final IR)
Initial High Risk and Low MRD (\<0.0001) at first time point (Day 32)
Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:
CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase \[by randomization or direct assignment\], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase \[by randomization or direct assignment\], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).
All treatment completed 24 months from date of complete remission.
Pegaspargase
Arm A: Standard/Fixed Dose Pegaspargase (2500 IU/m2 every 2 weeks) Arm B: Reduced Dose (PK-adjusted) Pegaspargase (Starting Dose: 2000 IU/m2) Arm X: Directly Assigned Standard Dose (2500 IU/m2): For all VHR and patients who decline randomization
Erwinia asparaginase
Only for patients with Pegaspargase allergy or silent inactivation.
CYTARABINE
Standard of Care
DEXAMETHASONE
Standard of Care
Dexrazoxane
Standard of Care
Doxorubicin
Standard of Care
HYDROCORTISONE
Standard of Care
MERCAPTOPURINE
Standard of Care
METHOTREXATE
Standard of Care
Vincristine
Standard of Care
Final High Risk (Final HR)
Initial Low Risk or Initial High Risk with High MRD (\>=0.0001) at first time point (Day 32) but low MRD (\<0.001) at second time point (week 10-12)
Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:
CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase \[by randomization or direct assignment\], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase \[by randomization or direct assignment\], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).
All treatment completed 24 months from date of complete remission.
Pegaspargase
Arm A: Standard/Fixed Dose Pegaspargase (2500 IU/m2 every 2 weeks) Arm B: Reduced Dose (PK-adjusted) Pegaspargase (Starting Dose: 2000 IU/m2) Arm X: Directly Assigned Standard Dose (2500 IU/m2): For all VHR and patients who decline randomization
Erwinia asparaginase
Only for patients with Pegaspargase allergy or silent inactivation.
CYTARABINE
Standard of Care
DEXAMETHASONE
Standard of Care
Dexrazoxane
Standard of Care
Doxorubicin
Standard of Care
HYDROCORTISONE
Standard of Care
MERCAPTOPURINE
Standard of Care
METHOTREXATE
Standard of Care
Vincristine
Standard of Care
Final Very High Risk (Final VHR)
Initial VHR or any patient with high MRD (\>=0.001) at second time point (week 10-12)
Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:
Consolidation IB/B-ALL (High-dose methotrexate + leucovorin, cyclophosphamide, etoposide, IT chemotherapy); Consolidation IB/T-ALL (nelararbine, cyclophosphamide, etoposide); Consolidation IC (High-dose cytarabine, etoposide, dexamethasone, pegaspargase \[by direct assignment\], IT chemotherapy); CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase \[by direct assignment\], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase \[by direct assignment\], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).
Dasatinib administered daily during all phases to pts with ABL1-class fusions. All treatment completed 24 months from date of complete remission.
Pegaspargase
Arm A: Standard/Fixed Dose Pegaspargase (2500 IU/m2 every 2 weeks) Arm B: Reduced Dose (PK-adjusted) Pegaspargase (Starting Dose: 2000 IU/m2) Arm X: Directly Assigned Standard Dose (2500 IU/m2): For all VHR and patients who decline randomization
Erwinia asparaginase
Only for patients with Pegaspargase allergy or silent inactivation.
Cyclophosphamide
Standard of Care
CYTARABINE
Standard of Care
DASATINIB
Standard of Care
DEXAMETHASONE
Standard of Care
Dexrazoxane
Standard of Care
Doxorubicin
Standard of Care
ETOPOSIDE
Standard of Care
HYDROCORTISONE
Standard of Care
LEUCOVORIN CALCIUM
Standard of Care
MERCAPTOPURINE
Standard of Care
METHOTREXATE
Standard of Care
NELARABINE
Standard of Care
Vincristine
Standard of Care
Fixed Dose Pegaspargase
Final LR, IR, HR patients who consent to randomization and are assigned to receive 15 doses of pegaspargase every 2-weeks at standard fixed-dose (2500 IU/m2/dose).
Pegaspargase
Arm A: Standard/Fixed Dose Pegaspargase (2500 IU/m2 every 2 weeks) Arm B: Reduced Dose (PK-adjusted) Pegaspargase (Starting Dose: 2000 IU/m2) Arm X: Directly Assigned Standard Dose (2500 IU/m2): For all VHR and patients who decline randomization
Erwinia asparaginase
Only for patients with Pegaspargase allergy or silent inactivation.
Reduced Dose (PK-Adjusted) Pegaspargase
Final LR, IR, HR patients who consent to randomization and are assigned to receive 15 doses of pegaspargase every 2-weeks beginning at a reduced dose (2000 IU/m2/dose); subsequent doses adjusted based on nadir serum asparaginase activity (NSAA) levels, with goal of maintaining NSAA between 0.4 and 1.0 IU/mL. Closed to Enrollment.
Pegaspargase
Arm A: Standard/Fixed Dose Pegaspargase (2500 IU/m2 every 2 weeks) Arm B: Reduced Dose (PK-adjusted) Pegaspargase (Starting Dose: 2000 IU/m2) Arm X: Directly Assigned Standard Dose (2500 IU/m2): For all VHR and patients who decline randomization
Erwinia asparaginase
Only for patients with Pegaspargase allergy or silent inactivation.
Direct Assignment
All VHR patients, and any Final LR, IR, HR patients who decline randomization: Assigned to receive standard dosing of pegaspargase (15 doses of pegaspargase every 2-weeks at standard fixed-dose; 2500 IU/m2/dose).
Pegaspargase
Arm A: Standard/Fixed Dose Pegaspargase (2500 IU/m2 every 2 weeks) Arm B: Reduced Dose (PK-adjusted) Pegaspargase (Starting Dose: 2000 IU/m2) Arm X: Directly Assigned Standard Dose (2500 IU/m2): For all VHR and patients who decline randomization
Erwinia asparaginase
Only for patients with Pegaspargase allergy or silent inactivation.
Interventions
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Pegaspargase
Arm A: Standard/Fixed Dose Pegaspargase (2500 IU/m2 every 2 weeks) Arm B: Reduced Dose (PK-adjusted) Pegaspargase (Starting Dose: 2000 IU/m2) Arm X: Directly Assigned Standard Dose (2500 IU/m2): For all VHR and patients who decline randomization
Erwinia asparaginase
Only for patients with Pegaspargase allergy or silent inactivation.
Cyclophosphamide
Standard of Care
CYTARABINE
Standard of Care
DASATINIB
Standard of Care
DEXAMETHASONE
Standard of Care
Dexrazoxane
Standard of Care
Doxorubicin
Standard of Care
ETOPOSIDE
Standard of Care
HYDROCORTISONE
Standard of Care
LEUCOVORIN CALCIUM
Standard of Care
MERCAPTOPURINE
Standard of Care
METHOTREXATE
Standard of Care
NELARABINE
Standard of Care
Vincristine
Standard of Care
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
\-- For patients with circulating blasts in the peripheral blood, flow cytometry confirmation of B-ALL or T-ALL phenotype is sufficient for registration onto the study. Bone marrow aspirate and/or biopsy should be performed as soon as feasible, preferably prior to the initiation of any therapy.
2. Prior Therapy: No prior therapy is allowed except for the following:
* Corticosteroids: Short courses of corticosteroid (defined as ≤ 7 days of corticosteroids within the 4-weeks preceding registration) are allowed prior to registration.
\--- Participants who have been on corticosteroids chronically (defined as more than 7 days of corticosteroids within the 4-weeks preceding registration or more than 28 days of corticosteroids over the preceding 6 months) are not eligible.
* IT cytarabine: A single dose of intrathecal cytarabine (at the time of the diagnostic lumbar puncture) is allowed prior to registration. If patient has received IT cytarabine prior to registration, Day 1 IT cytarabine should not be administered.
* Emergent Radiation Therapy: Emergent radiation to the mediastinum or other life-threatening masses is allowed prior to registration.
3. Age: 365 days to \< 22 years
4. Direct bilirubin \< 1.4 mg/dL (23.9 micromoles/L).
5. Ability of parent or guardian to understand and the willingness to sign a written informed consent document.
Exclusion Criteria
2. World Health Organization diagnostic criteria of mixed phenotype acute leukemia (MPAL) or leukemia of ambiguous lineage
3. Any chemotherapy or radiotherapy for previous malignancy are not eligible.
4. Treatment in past with any anti-neoplastic agent, including methotrexate, 6-mercaptopurine, 6-thioguanine, vincristine cyclophosphamide, cytarabine (except for IT cytarabine), or any anthracycline, for any reason (eg, rheumatologic or autoimmune condition).
5. Currently receiving any investigational agents.
6. Known HIV-positivity
7. Uncontrolled intercurrent illness including, but not limited to ongoing infection with vital sign instability (hypotension, respiratory insufficiency), life-threatening acute tumor lysis syndrome (eg, with renal failure), symptomatic congestive heart failure, cardiac arrhythmia, intracranial or other uncontrolled bleeding, or psychiatric illness/social situations that would limit compliance with study requirements.
8. Pregnant women are excluded from this study because many of the agents used on this protocol have potential for teratogenic and/or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with these chemotherapy agents, breastfeeding should be discontinued if the mother is enrolled.
9. History of a previous malignancy. Exception: Individuals with a previous malignancy treated with surgery only (no chemotherapy or radiotherapy) more than 5 years prior to registration may be enrolled.
1 Year
21 Years
ALL
No
Sponsors
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Servier
INDUSTRY
Dana-Farber Cancer Institute
OTHER
Responsible Party
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Melissa Burns
Principal Investigator
Principal Investigators
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Melissa Burns, MD
Role: PRINCIPAL_INVESTIGATOR
Dana-Farber Cancer Institute
Locations
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Boston Children's Hospital
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Columbia University Medical Center, Morgan Stanley Children's Hospital of New York-Presbyterian
New York, New York, United States
Montefiore Medical Center
The Bronx, New York, United States
Hasbro Children's Hospital / Rhode Island Hospital
Providence, Rhode Island, United States
Hospital Sainte Justine, University of Montreal
Montreal, Quebec, Canada
Centre Hospitalier U. de Quebec
Québec, Quebec, Canada
Countries
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References
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Park Y, K C N, Willekens J, Patel C, Savage BA, Lin H, Paneque A, Daly R, Thrope A, Burns MA, Welch JJG, Kahn JM, Kelly KM, Tran TH, Michon B, Gennarini L, Silverman LB, Sands SA, Cole PD. Treatment-Related Changes in Cerebrospinal Fluid Markers of Oxidative Stress and Neurodegeneration during Therapy for Childhood Acute Lymphoblastic Leukemia. Cancer Epidemiol Biomarkers Prev. 2025 Nov 3;34(11):2015-2024. doi: 10.1158/1055-9965.EPI-25-1058.
Tran TH, Langlois S, Meloche C, Caron M, Saint-Onge P, Rouette A, Bataille AR, Jimenez-Cortes C, Sontag T, Bittencourt H, Laverdiere C, Lavallee VP, Leclerc JM, Cole PD, Gennarini LM, Kahn JM, Kelly KM, Michon B, Santiago R, Stevenson KE, Welch JJG, Schroeder KM, Koch V, Cellot S, Silverman LB, Sinnett D. Whole-transcriptome analysis in acute lymphoblastic leukemia: a report from the DFCI ALL Consortium Protocol 16-001. Blood Adv. 2022 Feb 22;6(4):1329-1341. doi: 10.1182/bloodadvances.2021005634.
Other Identifiers
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16-001
Identifier Type: -
Identifier Source: org_study_id
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