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Trial record 18 of 120 for:    INCB018424

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Incyte Corporation
Sponsor:
Collaborator:
Children's Oncology Group
Information provided by (Responsible Party):
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT02723994
First received: March 9, 2016
Last updated: September 1, 2016
Last verified: September 2016
  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
B-cell 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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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) ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

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) ] [ Designated as safety issue: Yes ]

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

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

Inclusion Criteria:

  • 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
  • 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 ≥ 3 × 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02723994

Contacts
Contact: Incyte Corporation Call Center 1.855.463.3463

  Show 89 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 
Study First Received: March 9, 2016
Last Updated: September 1, 2016
Health Authority: United States: Food and Drug Administration

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
Burkitt Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoma
Dexamethasone
Prednisone
Pegaspargase
Methotrexate
Cyclophosphamide
Doxorubicin
Cytarabine
Vincristine
6-Mercaptopurine
Thioguanine
Asparaginase
Levoleucovorin

ClinicalTrials.gov processed this record on December 06, 2016