Clinical Trials /

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

NCT02723994

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia
  • Official Title: A Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib With Chemotherapy in Children With De Novo High-Risk CRLF2-Rearranged and/or JAK Pathway-Mutant Acute Lymphoblastic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: INCB 18424-269
  • SECONDARY ID: AALL1521
  • NCT ID: NCT02723994

Conditions

  • Leukemia

Interventions

DrugSynonymsArms
RuxolitinibINCB018424Ruxolitinib in combination with chemotherapy
Asparaginase Erwinia ChrysanthemiRuxolitinib in combination with chemotherapy
CyclophosphamideRuxolitinib in combination with chemotherapy
CytarabineRuxolitinib in combination with chemotherapy
DexamethasoneRuxolitinib in combination with chemotherapy
DoxorubicinRuxolitinib in combination with chemotherapy
Leucovorin CalciumRuxolitinib in combination with chemotherapy
MercaptopurineRuxolitinib in combination with chemotherapy
MethotrexateRuxolitinib in combination with chemotherapy
PegaspargaseRuxolitinib in combination with chemotherapy
PrednisoneRuxolitinib in combination with chemotherapy
ThioguanineRuxolitinib in combination with chemotherapy
Vincristine SulfateRuxolitinib in combination with chemotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Ruxolitinib in combination with chemotherapyExperimental
  • Ruxolitinib
  • Asparaginase Erwinia Chrysanthemi
  • Cyclophosphamide
  • Cytarabine
  • Dexamethasone
  • Doxorubicin
  • Leucovorin Calcium
  • Mercaptopurine
  • Methotrexate
  • Pegaspargase
  • Prednisone
  • Thioguanine
  • Vincristine Sulfate

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

               -  Systemic steroid pretreatment without presteroid WBC documentation

          -  One of the following Ph-like ALL genetic lesions must be present in the diagnostic
             bone marrow or peripheral blood sample:

               -  CRLF2 rearrangement with JAK1 or JAK2 mutation (JAK+)

               -  CRLF2 rearrangement without JAK mutation

               -  Other JAK pathway alterations (eg, JAK2 fusions, erythropoietin receptor (EPO-R)
                  fusions, SH2B3 deletions, interleukin-7 receptor-alpha (IL7RA) mutations) with or
                  without CRLF2 rearrangement

          -  Completed a 4-drug Induction therapy regimen (modified aBFM regimen or equivalent) in
             Study AALL1131 or as 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
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Safety/tolerability of ruxolitinib in combination with chemotherapy as measured by adverse events (AEs), vital signs, clinical laboratory tests, and echocardiograms
Time Frame: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)
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Time Frame: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)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • B-cell acute lymphoblastic leukemia (ALL)
  • pediatric
  • multi-agent chemotherapy
  • JAK inhibitor

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