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

Leukemia Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02723994
• Other study ID #: INCB 18424-269
• Secondary ID: AALL1521
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 30, 2016
• Est. completion date: February 1, 2026

Study information

• Verified date: January 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 171
• Est. completion date: February 1, 2026
• Est. primary completion date: February 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.
• Asparaginase Erwinia Chrysanthemi

• Cyclophosphamide

• Cytarabine

• Dexamethasone

• Doxorubicin

• Leucovorin Calcium

• Mercaptopurine

• Methotrexate

• Pegaspargase

• Prednisone

• Thioguanine

• Vincristine Sulfate

Locations

Country	Name	City	State
Canada	Alberta'S Children Hospital	Calgary	Alberta
Canada	McMaster University Medical Centre	Hamilton
Canada	Chu Sainte-Justine	Montreal	Quebec
Canada	McGill University Health Centre/Glen Site/Cedars Cancer Centre	Montreal	Quebec
Canada	The Hospital For Sick Children	Toronto	Ontario
Canada	Bc Children'S Hospital	Vancouver	British Columbia
Puerto Rico	San Jorge Childrens Hospital	San Juan
Puerto Rico	University Pediatric Hospital	San Juan
United States	Akron Children'S Hospital	Akron	Ohio
United States	Albany Medical College	Albany	New York
United States	University of New Mexico Hospital	Albuquerque	New Mexico
United States	Cs Mott Childrens Hospital	Ann Arbor	Michigan
United States	Egleston Children'S Health	Atlanta	Georgia
United States	Children'S Hospital Colorado	Aurora	Colorado
United States	Dell Childrens Medical Center of Central Texas	Austin	Texas
United States	Johns Hopkins University	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	The Childrens Hospital of Alabama	Birmingham	Alabama
United States	Dana Farber Boston Children'S	Boston	Massachusetts
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	University of North Carolina At Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Ann & Robert H. Lurie Children'S Hospital	Chicago	Illinois
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Rainbow Babies & Children Hosp	Cleveland	Ohio
United States	Nationwide Children'S Hospital	Columbus	Ohio
United States	Driscoll Children'S Hospital	Corpus Christi	Texas
United States	Medical City Dallas Hospital	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Dayton Children'S Hospital	Dayton	Ohio
United States	Blank Childrens Hospital	Des Moines	Iowa
United States	El Paso Children'S Hospital Corporation	El Paso	Texas
United States	Kaiser Permanente	Fontana	California
United States	Childrens Hospital of Southwest Florida	Fort Myers	Florida
United States	Helen Devos Childrens Hosp	Grand Rapids	Michigan
United States	St Vincent Hospital	Green Bay	Wisconsin
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children'S Medical Ctr	Hartford	Connecticut
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	Joe Dimaggio Children Hospital	Hollywood	Florida
United States	Kapiolani Medical Center For Women and Children	Honolulu	Hawaii
United States	Texas Childrens Hospital	Houston	Texas
United States	Riley Hospital For Children	Indianapolis	Indiana
United States	St Vincent Hospital	Indianapolis	Indiana
United States	University of Iowa Hospital and Clinics	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Childrens Clinic	Jacksonville	Florida
United States	University of Florida Health Shands Hospital	Jacksonville	Florida
United States	The Children'S Mercy Hospital Outpatient	Kansas City	Missouri
United States	Michigan State University	Lansing	Michigan
United States	Alliance For Childhood Diseases	Las Vegas	Nevada
United States	Children'S Center For Cancer & Blood Dis	Las Vegas	Nevada
United States	University of Kentucky	Lexington	Kentucky
United States	Arkansas Childrens Hospital	Little Rock	Arkansas
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	Kosair Childrens Hospital	Louisville	Kentucky
United States	Valley Childrens Hospital	Madera	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Children'S Hospitals and Clinics of Minnesota	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	Morristown Medical Center	Morristown	New Jersey
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of Nj	New Brunswick	New Jersey
United States	Smilow Cancer Center - Yale	New Haven	Connecticut
United States	Cohen Children'S Medical Center	New Hyde Park	New York
United States	Ochsner Clinic	New Orleans	Louisiana
United States	Nyu Clinical Cancer Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Children'S Hospital of the	Norfolk	Virginia
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Children'S Hospital & Medical Center	Omaha	Nebraska
United States	Choc Children Hospital	Orange	California
United States	Arnold Palmer Hospital For Children	Orlando	Florida
United States	Florida Hospital Orlando	Orlando	Florida
United States	Lucille Packard Childrens Hospital	Palo Alto	California
United States	St Josephs Regional Medical Center	Paterson	New Jersey
United States	Nemours Childrens Clinic	Pensacola	Florida
United States	Children'S Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children'S Hospital	Phoenix	Arizona
United States	Childrens Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Doernbecher Childrens Hospital	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Hasbro Childrens Hospital	Providence	Rhode Island
United States	University of Rochester Medical Center	Rochester	New York
United States	Washington University	Saint Louis	Missouri
United States	All Childrens Hospital	Saint Petersburg	Florida
United States	Primary Children'S Hospital	Salt Lake City	Utah
United States	University of Texas Health Science Cente	San Antonio	Texas
United States	Kaiser Permanente	San Diego	California
United States	Rady Children'S Hospital - San Diego	San Diego	California
United States	Ucsf Pediatric Oncology	San Francisco	California
United States	Kaiser Permanente Downey	Santa Fe Springs	California
United States	Maine Center For Cancer Medicine	Scarborough	Maine
United States	Seattle Children'S Hospital	Seattle	Washington
United States	Providence Sacred Heart Medical Center & Children'S Hospital	Spokane	Washington
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Suny Upstate Medical University	Syracuse	New York
United States	St Josephs Childrens Hospital Tampa	Tampa	Florida
United States	Toledo Hospital	Toledo	Ohio
United States	New York Medical College	Valhalla	New York
United States	Saint Marys Medical Center	West Palm Beach	Florida
United States	Alfred I. Dupont Hospital For Children	Wilmington	Delaware
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Incyte Corporation	Children's Oncology Group

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)