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

This study is currently recruiting participants.
Verified December 2017 by Incyte Corporation
Sponsor:
ClinicalTrials.gov Identifier:
NCT02723994
First Posted: March 31, 2016
Last Update Posted: December 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Children's Oncology Group
Information provided by (Responsible Party):
Incyte Corporation
  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.

Condition Intervention Phase
ALL (Acute Lymphoblastic Leukemia) 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 2

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Incyte Corporation:

Primary Outcome Measures:
  • 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) ]
  • 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 [ Time Frame: Part 2: assessed at 3 years ]

Secondary Outcome Measures:
  • 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) ]

Estimated Enrollment: 170
Study Start Date: August 2016
Estimated Study Completion Date: May 2024
Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ruxolitinib in combination with chemotherapy Drug: Ruxolitinib
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.
Other Name: INCB018424
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

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02723994


Contacts
Contact: Incyte Corporation Call Center 1.855.463.3463

  Show 114 Study Locations
Sponsors and Collaborators
Incyte Corporation
Children's Oncology Group
Investigators
Study Director: Albert Assad, MD Incyte Corporation
Study Chair: Sarah Tasian, MD Children's Hospital of Philadelphia, Philadelphia, PA
Study Chair: Mignon Loh, MD UCSF Benioff Children's Hospital, San Francisco, CA
  More Information

Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT02723994     History of Changes
Other Study ID Numbers: INCB 18424-269
AALL1521 ( Other Identifier: Children's Oncology Group )
First Submitted: March 9, 2016
First Posted: March 31, 2016
Last Update Posted: December 11, 2017
Last Verified: December 2017

Keywords provided by Incyte Corporation:
B-cell acute lymphoblastic leukemia (ALL)
pediatric
multi-agent chemotherapy
JAK inhibitor

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Prednisone
Pegaspargase
Cyclophosphamide
Doxorubicin
Methotrexate
Cytarabine
Vincristine
Asparaginase
6-Mercaptopurine
Thioguanine
Levoleucovorin
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists