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

ID#: NCT03007147

Age: 2 - 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 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.

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)

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