A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia

Incyte

Status and phase: Active, not recruiting; Phase 2

Conditions: Leukemia

Treatments: Drug: Methotrexate; Drug: Thioguanine; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Ruxolitinib; Drug: Cytarabine; Drug: Leucovorin Calcium; Drug: Mercaptopurine; Drug: Prednisone; Drug: Asparaginase Erwinia Chrysanthemi; Drug: Dexamethasone; Drug: Vincristine Sulfate; Drug: Pegaspargase

Study type: Interventional

Funder types: NETWORK; Industry

Identifiers

NCT02723994

AALL1521 (Other Identifier)

INCB 18424-269

Details and patient eligibility

About

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.

Enrollment: 171 patients

Sex: All

Ages: 1 to 21 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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171 participants in 1 patient group

Ruxolitinib in combination with chemotherapy

Experimental group

Treatment:

Drug: Pegaspargase

Drug: Vincristine Sulfate

Drug: Dexamethasone

Drug: Asparaginase Erwinia Chrysanthemi

Drug: Prednisone

Drug: Mercaptopurine

Drug: Leucovorin Calcium

Drug: Cytarabine

Drug: Cyclophosphamide

Drug: Ruxolitinib

Drug: Thioguanine

Drug: Doxorubicin

Drug: Methotrexate