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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03007147
Ethics application status
Date submitted
28/12/2016
Date registered
2/01/2017
Date last updated
27/08/2020

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 - Cyclophosphamide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Daunorubicin Hydrochloride
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Dexrazoxane Hydrochloride
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Etoposide
Other interventions - 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: 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

Other interventions: 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
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease free survival (DFS) - Will compare the DFS of standard risk Philadelphia chromosome (Ph+) acute lymphoblastic leukemia (ALL) patients treated continuous imatinib mesylate with high risk Children's Oncology Group (COG)-ALL chemotherapy backbone or more intensive European (Es)PhALL chemotherapy backbone.
Timepoint [1] 0 0
From randomization to first event (relapse, second malignancy, or death in complete remission) or time to last follow-up for patients without events, assessed up to 3 years
Secondary outcome [1] 0 0
Imatinib mesylate administration after allogeneic hematopoietic stem cell transplantation (HSCT) in high risk Ph+ ALL patients - Feasibility of post-HSCT imatinib mesylate is determined based on the proportion of patients who receive at least 75% of intended doses.
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [2] 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 - Will be estimated using the Kaplan-Meier method and standard errors estimated by Greenwood.
Timepoint [2] 0 0
From the date of bone marrow for minimal residual disease (MRD) assessment at end-IB to first event or time to last follow-up for patients without events, assessed up to 3 years
Secondary outcome [3] 0 0
Incidence of grade 3 or higher infections in standard risk Ph+ ALL patients in the two randomized arms - Evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The rate of infections during the post IB/pre-maintenance phases of treatment will be compared accounting for follow-up time.
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
EFS of all enrolled patients - Will be estimated using the Kaplan-Meier method and standard errors estimated by Greenwood.
Timepoint [4] 0 0
From enrollment until the first occurrence of: M3 marrow at the end of Induction IA, relapse, second malignancy, or death as a first event, assessed up to 3 years
Secondary outcome [5] 0 0
Overall survival (OS) of all enrolled patients - Will be estimated using the Kaplan-Meier method and standard errors estimated by Greenwood. Will be estimated with a maximum standard error of 1.9%.
Timepoint [5] 0 0
From study enrollment to death from any cause, assessed up to 3 years
Secondary outcome [6] 0 0
OS of standard risk patients - Will be estimated using the Kaplan-Meier method and standard errors estimated by Greenwood. Estimates will also be calculated for each of the randomization groups.
Timepoint [6] 0 0
From randomization to death from any cause, assessed up to 3 years
Secondary outcome [7] 0 0
OS of high risk patients - Will be estimated using the Kaplan-Meier method and standard errors estimated by Greenwood. Estimates will also be calculated for each of the randomization groups.
Timepoint [7] 0 0
From the date of MRD assessment at end-IB to death from any cause, assessed 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 must be
submitted for rapid central review within 72 hours of study enrollment

- 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 reverse
transcriptase (RT)-PCR

- Patient must have previously started induction therapy, which includes vincristine, a
corticosteroid, pegaspargase, with or without anthracycline, and/or other standard
cytotoxic chemotherapy

- Patient has not received more than 14 days of multiagent induction therapy beginning
with the first dose of vinCRIStine

- Patient may have started imatinib prior to study entry but has not received more than
14 days of imatinib

- 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 is not required if echocardiogram was obtained within
21 days of study enrollment

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2

- 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
2 Years
Maximum age
21 Years
Gender
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 their study participation

- Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart
block

- Prior treatment with dasatinib, or any BCR-ABL1 inhibitor other than imatinib

- All patients and/or their parents or legal guardians must sign a written informed
consent

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met

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
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
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United States of America
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Alabama
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United States of America
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Alaska
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Arkansas
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Connecticut
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Delaware
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Zurich,

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

Ethics approval
Ethics application status

Summary
Brief summary
This randomized phase III trial studies how well imatinib mesylate and combination
chemotherapy work in treating patients with newly diagnosed Philadelphia chromosome positive
acute lymphoblastic leukemia. Imatinib mesylate may stop the growth of cancer cells by
blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, work in
different ways to stop the growth of cancer cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Giving imatinib mesylate and
combination chemotherapy may work better in treating patients with Philadelphia chromosome
positive acute lymphoblastic leukemia.
Trial website
https://clinicaltrials.gov/show/NCT03007147
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Lewis B Silverman, MD
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

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03007147