Leukemia
Conditions
Keywords
B-cell acute lymphoblastic leukemia (ALL), pediatric, multi-agent chemotherapy, JAK inhibitor
Brief summary
This is a nonrandomized study of ruxolitinib in combination with a standard multi-agent chemotherapy regimen for the treatment of B-cell acute lymphoblastic leukemia. Part 1 of the study will optimize the dose of study drug (ruxolitinib) in combination with the chemotherapy regimen. Part 2 will evaluate the efficacy of combination chemotherapy and ruxolitinib at the recommended dose determined in Part 1.
Interventions
DRUGRuxolitinib
In Part 1, ruxolitinib will be administered at a protocol-defined starting dose in combination with chemotherapy, with dose escalation and de-escalation following the rolling 6 study design. The established recommended starting dose will be taken forward into Part 2.
DRUGCyclophosphamide
DRUGCytarabine
DRUGDexamethasone
DRUGDoxorubicin
DRUGLeucovorin Calcium
DRUGMercaptopurine
DRUGMethotrexate
DRUGPegaspargase
DRUGPrednisone
DRUGThioguanine
DRUGVincristine Sulfate
Sponsors
Incyte Corporation
Children's Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Eligible for study when participant is 1 year to 21 years at the time of diagnosis * Eligible Ages in Canada; 2 years to 21 years * De novo high-risk (HR) Ph-like B-ALL for which any of following criteria are present at diagnosis: * Age ≥ 10 years * White blood cell (WBC) ≥ 50 × 10\^3/μL * CNS3 leukemia at diagnosis * Systemic steroid pretreatment without presteroid WBC documentation * Diagnostic bone marrow or peripheral blood sample must have gene expression profiling and downstream genetic testing performed by submitting diagnostic specimens under the COG AALL08B1 or APEC14B1 biology studies, or AALL1131 or its successor study. Specimens must demonstrate a Ph-like expression profile (ie, LDA-positive) as tested by low density microarray testing at the COG ALL reference laboratory or TriCore laboratory at the University of New Mexico AND must contain 1 of the following genetic lesions: (determined at COG ALL reference laboratories, or equivalent CAP/CLIA-certified laboratories approved by the medical monitor: 1. CRLF2 rearrangement with confirmed JAK1 or JAK2 mutation (JAK+) 2. CRLF2 rearrangement without JAK mutation 3. Other JAK pathway alterations (eg, JAK2 fusions, EPOR fusions, SH2B3 deletions, IL7RA mutations) with or without CRLF2-R, or CRLF2-R with unknown JAK status as determined by a COG ALL Reference Laboratory * Completed a 4-drug Induction therapy regimen (modified aBFM regimen or equivalent) in Study AALL1131 or its successor study, or as per the institutional standard of care for HR B-ALL and have had end-Induction minimal residual disease (MRD) assessed * Male and female subjects of reproductive non childbearing potential or willing to take appropriate precautions to avoid pregnancy or fathering a child for the duration of study participation
Exclusion criteria
* Receipt of any other cytotoxic chemotherapy before Induction therapy, with exception of hydroxyurea or steroid pretreatment * Trisomy 21 (Down syndrome) * BCR-ABL1-rearranged (Ph+) ALL * Calculated creatinine clearance or radioisotope glomerular filtration rate \< 70 mL/min/1.73 m\^2 * Alanine aminotransferase ≥ 5 × upper limit of normal (ULN) for age * Direct bilirubin ≥ 1.5 × ULN (may be assumed if total bilirubin is below ULN) * History or evidence of cirrhosis * Platelet count \< 75 × 10\^3/μL * Absolute neutrophil count (ANC) \< 750/μL * Positive screen for hepatitis B or C * Known human immunodeficiency virus infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: Safety/tolerability of ruxolitinib in combination with chemotherapy as measured by adverse events (AEs), vital signs, clinical laboratory tests, and echocardiograms | Part 1: AEs assessed from screening through up to 30 days after the last dose of study drug, expected to be 26 months (females) or 38 months (males) |
| Part 2: Efficacy of ruxolitinib in combination with chemotherapy as measured by Event-free survival, defined as the percentage of patients alive without relapse, progression, or death at 3 years from study Day 1 | Part 2: assessed at 3 years |
Secondary
| Measure | Time frame |
|---|---|
| Safety and tolerability of the combination treatment for subjects beginning treatment at the recommended dose for Part 2, as assessed by AEs, vital signs, clinical laboratory tests, and echocardiograms | AEs assessed from screening through up to 30 days after the last dose of study treatment, expected to be 26 months (females) or 38 months (males) |
Countries
Canada, Puerto Rico, United States
Contacts
STUDY_DIRECTORAlbert Assad, MD
Incyte Corporation
STUDY_CHAIRSarah Tasian, MD
Children's Hospital of Philadelphia, Philadelphia, PA
Outcome results
None listed