Current Environment:

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.

Conditions

Leukemia

Recruitment Status

Recruiting

Eligibility Criteria

Inclusion Criteria:

Eligible for study when participant is 1 year to 21 years at the time of diagnosis
Eligible Ages in Australia and 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:

CRLF2 rearrangement* with confirmed JAK1 or JAK2 mutation (JAK+)
CRLF2 rearrangement* without JAK mutation
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

Intervention

Intervention Type

Intervention Name

Drug

Ruxolitinib

Drug

Asparaginase Erwinia Chrysanthemi

Drug

Cyclophosphamide

Drug

Cytarabine

Drug

Dexamethasone

Drug

Doxorubicin

Drug

Leucovorin Calcium

Drug

Mercaptopurine

Drug

Methotrexate

Drug

Pegaspargase

Drug

Prednisone

Drug

Thioguanine

Drug

Vincristine Sulfate

Phase

Phase 2

Gender

All

Minimum Age

1 Year

Maximum Age

21 Years

Download Date

February 24, 2022

Principal Investigator

N/A

Primary Contact Information

Incyte Corporation Call Center

1.855.463.3463

For more information on this trial, visit clinicaltrials.gov.

Contact

For more information and to contact the study team: