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

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ClinicalTrials.gov Identifier: NCT02723994
Recruitment Status : Recruiting
First Posted : March 31, 2016
Last Update Posted : October 31, 2019
Sponsor:
Collaborator:
Children's Oncology Group
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
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

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
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
Study Start Date : August 2016
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : May 2024


Arm Intervention/treatment
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



Primary Outcome Measures :
  1. 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) ]
  2. 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 :
  1. 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) ]


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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 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:

    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

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
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Contact: Incyte Corporation Call Center 1.855.463.3463

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Sponsors and Collaborators
Incyte Corporation
Children's Oncology Group
Investigators
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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

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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 Posted: March 31, 2016    Key Record Dates
Last Update Posted: October 31, 2019
Last Verified: October 2019
Keywords provided by Incyte Corporation:
B-cell acute lymphoblastic leukemia (ALL)
pediatric
multi-agent chemotherapy
JAK inhibitor
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Dexamethasone
Prednisone
Cyclophosphamide
Doxorubicin
Methotrexate
Vincristine
Asparaginase
Mercaptopurine
Pegaspargase
Thioguanine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal