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

Phase 2

Active, not recruiting

• Conditions: Leukemia
• Interventions: 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

• Registration Number: NCT02723994
• Lead Sponsor: Incyte Corporation

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-03-09
• Study First Submitted QC: 2016-03-24
• Study First Posted: 2016-03-31
• Study Start: 2016-09-30
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-30
• Last Update Posted: 2025-05-02
• Primary Completion: 2026-02-01
• Study Completion: 2026-02-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 171

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ruxolitinib in combination with chemotherapy	Dexamethasone	-
Ruxolitinib in combination with chemotherapy	Leucovorin Calcium	-
Ruxolitinib in combination with chemotherapy	Asparaginase Erwinia Chrysanthemi	-
Ruxolitinib in combination with chemotherapy	Doxorubicin	-
Ruxolitinib in combination with chemotherapy	Pegaspargase	-
Ruxolitinib in combination with chemotherapy	Cytarabine	-
Ruxolitinib in combination with chemotherapy	Ruxolitinib	-
Ruxolitinib in combination with chemotherapy	Methotrexate	-
Ruxolitinib in combination with chemotherapy	Thioguanine	-
Ruxolitinib in combination with chemotherapy	Vincristine Sulfate	-
Ruxolitinib in combination with chemotherapy	Mercaptopurine	-
Ruxolitinib in combination with chemotherapy	Prednisone	-
Ruxolitinib in combination with chemotherapy	Cyclophosphamide	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (108)

The Childrens Hospital of Alabama; 🇺🇸 Birmingham, Alabama, United States

Phoenix Children'S Hospital; 🇺🇸 Phoenix, Arizona, United States

Arkansas Childrens Hospital; 🇺🇸 Little Rock, Arkansas, United States

Kaiser Permanente; 🇺🇸 San Diego, California, United States

Loma Linda University Cancer Center; 🇺🇸 Loma Linda, California, United States

Miller Childrens Hospital Pharmacy; 🇺🇸 Long Beach, California, United States

Children'S Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Kaiser Foundation Health Plan; 🇺🇸 Los Angeles, California, United States

Southern California Permanente Medical Group; 🇺🇸 Los Angeles, California, United States

Valley Childrens Hospital; 🇺🇸 Madera, California, United States

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