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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
4/12/2024

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
8/08/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2027
Actual
Sample size
Target
475
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
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United States of America
State/province [2] 0 0
Alaska
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United States of America
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Arizona
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United States of America
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Arkansas
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California
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State/province [6] 0 0
Colorado
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Connecticut
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Delaware
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District of Columbia
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United States of America
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Florida
Country [11] 0 0
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Iowa
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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.

Results not provided in https://clinicaltrials.gov/study/NCT03007147