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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03007147




Registration number
NCT03007147
Ethics application status
Date submitted
28/12/2016
Date registered
2/01/2017
Date last updated
15/08/2024

Titles & IDs
Public title
Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
Scientific title
International Phase 3 Trial in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL) Testing Imatinib in Combination With Two Different Cytotoxic Chemotherapy Backbones
Secondary ID [1] 0 0
NCI-2016-01588
Secondary ID [2] 0 0
AALL1631
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukemia 0 0
B Acute Lymphoblastic Leukemia 0 0
Mixed Phenotype Acute Leukemia 0 0
T Acute Lymphoblastic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Allogeneic Hematopoietic Stem Cell Transplantation
Treatment: Drugs - Calaspargase Pegol
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Daunorubicin Hydrochloride
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Dexrazoxane Hydrochloride
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Etoposide
Treatment: Other - Filgrastim
Treatment: Drugs - Ifosfamide
Treatment: Drugs - Imatinib Mesylate
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Leucovorin Calcium
Treatment: Drugs - Mercaptopurine
Treatment: Drugs - Mercaptopurine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Methylprednisolone
Treatment: Drugs - Pegaspargase
Treatment: Drugs - Prednisolone
Other interventions - Questionnaire Administration
Treatment: Drugs - Therapeutic Hydrocortisone
Treatment: Drugs - Thioguanine
Treatment: Drugs - Vincristine Sulfate

Experimental: Arm A (imatinib mesylate, EsPhALL chemotherapy) - See Detailed Description

Experimental: Arm B (imatinib mesylate, COG/BFM chemotherapy) - See Detailed Description.

Experimental: Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) - See Detailed Description


Treatment: Surgery: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo HSCT

Treatment: Drugs: Calaspargase Pegol
Given IV

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Cytarabine
Given IV, SC, or IT

Treatment: Drugs: Daunorubicin Hydrochloride
Given IV

Treatment: Drugs: Dexamethasone
Given PO or IV

Treatment: Drugs: Dexrazoxane Hydrochloride
Given IV

Treatment: Drugs: Doxorubicin
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Other: Filgrastim
Given IV

Treatment: Drugs: Ifosfamide
Given IV

Treatment: Drugs: Imatinib Mesylate
Given PO

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Leucovorin Calcium
Given PO or IV

Treatment: Drugs: Mercaptopurine
Given PO

Treatment: Drugs: Mercaptopurine
Given PO

Treatment: Drugs: Methotrexate
Given IT

Treatment: Drugs: Methylprednisolone
Given IV

Treatment: Drugs: Pegaspargase
Given IV

Treatment: Drugs: Prednisolone
Given PO

Other interventions: Questionnaire Administration
Ancillary studies

Treatment: Drugs: Therapeutic Hydrocortisone
Given IT

Treatment: Drugs: Thioguanine
Given PO

Treatment: Drugs: Vincristine Sulfate
Given IV

Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Treatment: Other
Intervention code [4] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease free survival (DFS) of Randomized Arms (standard risk [SR] Philadelphia chromosome [Ph+] acute lymphoblastic leukemia [ALL] patients)
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [1] 0 0
DFS on Randomized Arms (SR Ph+ ALL and ABL-class fusion positive patients)
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Feasibility of post hematopoietic stem cell transplantation (HSCT) imatinib mesylate administration after allogenic HSCT in high risk Ph+ ALL patients
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [3] 0 0
Event free survival (EFS) of high risk pediatric Ph+ ALL patients treated with EsPhALL chemotherapy, HSCT in first complete remission, and post-HSCT imatinib mesylate
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
Incidence of grade 3 or higher infections in standard risk Ph+ ALL patients in the two randomized arms
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [5] 0 0
EFS of all Ph+ patients
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [6] 0 0
Overall survival (OS) of all Ph+ patients
Timepoint [6] 0 0
Up to 3 years
Secondary outcome [7] 0 0
OS of SR Ph+ patients
Timepoint [7] 0 0
Up to 3 years
Secondary outcome [8] 0 0
OS of SR Ph+ patients by randomization group
Timepoint [8] 0 0
Up to 3 years
Secondary outcome [9] 0 0
OS of high risk Ph+ patients
Timepoint [9] 0 0
Up to 3 years
Secondary outcome [10] 0 0
EFS of all eligibility ABL-class fusion positive ALL patients
Timepoint [10] 0 0
Up to 3 years
Secondary outcome [11] 0 0
OS of all eligibility ABL-class fusion positive ALL patients
Timepoint [11] 0 0
Up to 3 years

Eligibility
Key inclusion criteria
* For patients enrolled on APEC14B1 prior to enrollment on AALL1631, the required diagnostic bone marrow sample has been fulfilled

* For patients who have not previously enrolled on APEC14B1 prior to enrollment on AALL1631, a baseline diagnostic sample (or peripheral blood sample with blasts if marrow sample unavailable) must be available to develop an MRD probe
* In addition, laboratory reports detailing evidence of BCR-ABL1 fusion or ABL-class fusion must be submitted for rapid central review within 72 hours of study enrollment
* >= 1 year (365 days) and =< 21 years at ALL diagnosis
* Ph+ (BCR-ABL1 fusion): newly diagnosed de novo ALL (B-ALL or T-ALL) or mixed phenotypic acute leukemia (MPAL meeting 2016 World Health Organization [WHO] definition) with definitive evidence of BCR-ABL1 fusion by karyotype, fluorescence in situ hybridization (FISH) and/or molecular methodologies
* ABL-class fusion: newly diagnosed B-ALL with definitive evidence of ABL-class fusions. ABL-class fusions are defined as those involving the following genes: ABL1, ABL2, CSF1R, PDGFRB, PDGFRA. Methods of detection include fluorescence in-situ hybridization (FISH, e.g. using break-apart or colocalization signals probes), multiplex or singleplex reverse-transcription polymerase chain reaction (RT-PCR), whole transcriptome or panel-based ribonucleic acid (RNA)-sequencing (e.g. TruSight RNA Pan-Cancer Panel; Illumina, San Diego, CA, USA or similar)
* Ph+ patients must have previously started Induction therapy, which includes vincristine, a corticosteroid, pegaspargase, with or without anthracycline, and/or other standard cytotoxic chemotherapy
* Ph+ patients have not received more than 14 days of multiagent Induction therapy beginning with the first dose of vinCRIStine
* Ph+ patients may have started imatinib prior to study entry but have not received more than 14 days of imatinib
* ABL-class fusion patients must have previously completed the 4 or 5 weeks of multiagent Induction chemotherapy (Induction IA phase)
* ABL-class fusion patients may have started imatinib during Induction IA, at the same time of or after the first vinCRIStine dose
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2
* Direct bilirubin =< 2.0 mg/dL
* Shortening fraction of >= 27% by echocardiogram
* Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram
* Corrected QT interval, QTc < 480 msec

* Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis, before study enrollment
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or serum creatinine within normal limits based on age/gender, as follows:

* 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
* 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
* 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)
* 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
* 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
* >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
Minimum age
1 Year
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Known history of chronic myelogenous leukemia (CML)
* ALL developing after a previous cancer treated with cytotoxic chemotherapy
* Active, uncontrolled infection, or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
* Down syndrome
* Pregnancy and breast feeding

* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of treatment according to protocol
* Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart block
* Prior treatment with dasatinib, or any TKI other than imatinib

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [5] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [6] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
6008 - Perth
Recruitment postcode(s) [6] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
Country [4] 0 0
United States of America
State/province [4] 0 0
Arkansas
Country [5] 0 0
United States of America
State/province [5] 0 0
California
Country [6] 0 0
United States of America
State/province [6] 0 0
Colorado
Country [7] 0 0
United States of America
State/province [7] 0 0
Connecticut
Country [8] 0 0
United States of America
State/province [8] 0 0
Delaware
Country [9] 0 0
United States of America
State/province [9] 0 0
District of Columbia
Country [10] 0 0
United States of America
State/province [10] 0 0
Florida
Country [11] 0 0
United States of America
State/province [11] 0 0
Georgia
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United States of America
State/province [12] 0 0
Hawaii
Country [13] 0 0
United States of America
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Idaho
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United States of America
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Illinois
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Indiana
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United States of America
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Iowa
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United States of America
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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Nebraska
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Nevada
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New Hampshire
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New Jersey
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New Mexico
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New York
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North Carolina
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South Dakota
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Tennessee
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Austria
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Vienna
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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Canada
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Saskatchewan
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Chile
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Santiago
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Czechia
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Praha
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Finland
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Tampere
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France
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Rennes
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Germany
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Schleswig-Holstein
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Germany
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Hamburg
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Hong Kong
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Kowloon
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Israel
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Central District
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Italy
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Monza
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Netherlands
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Utrecht
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New Zealand
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Auckland
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New Zealand
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Christchurch
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Puerto Rico
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Caguas
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Puerto Rico
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San Juan
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Saudi Arabia
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Riyadh
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Sweden
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Scania
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Switzerland
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Zurich

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
EsPhALL
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
National Cancer Institute (NCI)
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Lewis B Silverman
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.