Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

ID#: NCT03007147

Age: 1 year - 21 years

Gender: All

Healthy Subjects: No

Study Phase: Phase 3

Recruitment Status: Recruiting

Start Date: July 28, 2017

End Date: June 30, 2028

Summary: This randomized phase III trial studies how well imatinib mesylate works in combination with two different chemotherapy regimens in treating patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (ALL). Imatinib mesylate has been shown to improve outcomes in children and adolescents with Philadelphia chromosome positive (Ph+) ALL when given with strong chemotherapy, but the combination has many side effects. This trial is testing whether a different chemotherapy regimen may work as well as the stronger one but have fewer side effects when given with imatinib. The trial is also testing how well the combination of chemotherapy and imatinib works in another group of patients with a type of ALL that is similar to Ph+ ALL. This type of ALL is called "ABL-class fusion positive ALL", and because it is similar to Ph+ ALL, is thought it will respond well to the combination of agents used to treat Ph+ ALL.
Eligibility:

Inclusion Criteria:

- Diagnostic samples will be collected and analyzed according to the procedures of the National front-line protocol

- Patients should be enrolled on National ALL protocol prior to enrollment on EsPhALL2017/COGAALL1631. Regardless of initial front-line protocol baseline diagnostic samples must be available to develop an MRD probe

- BCR-ABL1 fusion (Ph+): newly diagnosed 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

- ABL-class fusion: newly diagnosed B-ALL with definitive evidence of ABL-class fusions identified according to National/Center procedures of each participating country. ABL-class fusions are defined as those involving the following genes: ABL1, ABL2, CSF1R, PDGFRB, PDGFRA, LYN. 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

- Regardless of initial front-line protocol, laboratory reports detailing evidence of BCR-ABL1 or ABL-class fusion must be available for the National Trial Unit

- Ph+ ALL patients must have previously started induction therapy, which includes vincristine, a corticosteroid, usually PEG-L-asparaginase, with or without anthracycline, and/or other standard cytotoxic chemotherapy

- Ph+ ALL patients have not received more than 14 days of multiagent induction therapy beginning with the first dose of vincristine

- Ph+ ALL 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

- 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)

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 inhibitor other than imatinib

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