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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02723994




Registration number
NCT02723994
Ethics application status
Date submitted
9/03/2016
Date registered
31/03/2016
Date last updated
31/10/2019

Titles & IDs
Public title
A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia
Scientific 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
Secondary ID [1] 0 0
AALL1521
Secondary ID [2] 0 0
INCB 18424-269
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Ruxolitinib
Treatment: Drugs - Asparaginase Erwinia Chrysanthemi
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Leucovorin Calcium
Treatment: Drugs - Mercaptopurine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Pegaspargase
Treatment: Drugs - Prednisone
Treatment: Drugs - Thioguanine
Treatment: Drugs - Vincristine Sulfate

Experimental: Ruxolitinib in combination with chemotherapy -


Treatment: Drugs: 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.

Treatment: Drugs: Asparaginase Erwinia Chrysanthemi


Treatment: Drugs: Cyclophosphamide


Treatment: Drugs: Cytarabine


Treatment: Drugs: Dexamethasone


Treatment: Drugs: Doxorubicin


Treatment: Drugs: Leucovorin Calcium


Treatment: Drugs: Mercaptopurine


Treatment: Drugs: Methotrexate


Treatment: Drugs: Pegaspargase


Treatment: Drugs: Prednisone


Treatment: Drugs: Thioguanine


Treatment: Drugs: Vincristine Sulfate


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Safety/tolerability of ruxolitinib in combination with chemotherapy as measured by adverse events (AEs), vital signs, clinical laboratory tests, and echocardiograms
Timepoint [1] 0 0
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 outcome [2] 0 0
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
Timepoint [2] 0 0
Part 2: assessed at 3 years
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
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)

Eligibility
Key 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
Minimum age
1 Year
Maximum age
21 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [2] 0 0
Royal Children's Hospital, Melbourne - Parkville
Recruitment postcode(s) [1] 0 0
- South Brisbane
Recruitment postcode(s) [2] 0 0
- Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
Florida
Country [9] 0 0
United States of America
State/province [9] 0 0
Georgia
Country [10] 0 0
United States of America
State/province [10] 0 0
Hawaii
Country [11] 0 0
United States of America
State/province [11] 0 0
Illinois
Country [12] 0 0
United States of America
State/province [12] 0 0
Indiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Iowa
Country [14] 0 0
United States of America
State/province [14] 0 0
Kentucky
Country [15] 0 0
United States of America
State/province [15] 0 0
Maine
Country [16] 0 0
United States of America
State/province [16] 0 0
Maryland
Country [17] 0 0
United States of America
State/province [17] 0 0
Massachusetts
Country [18] 0 0
United States of America
State/province [18] 0 0
Michigan
Country [19] 0 0
United States of America
State/province [19] 0 0
Minnesota
Country [20] 0 0
United States of America
State/province [20] 0 0
Mississippi
Country [21] 0 0
United States of America
State/province [21] 0 0
Missouri
Country [22] 0 0
United States of America
State/province [22] 0 0
Nebraska
Country [23] 0 0
United States of America
State/province [23] 0 0
Nevada
Country [24] 0 0
United States of America
State/province [24] 0 0
New Jersey
Country [25] 0 0
United States of America
State/province [25] 0 0
New Mexico
Country [26] 0 0
United States of America
State/province [26] 0 0
New York
Country [27] 0 0
United States of America
State/province [27] 0 0
North Carolina
Country [28] 0 0
United States of America
State/province [28] 0 0
Ohio
Country [29] 0 0
United States of America
State/province [29] 0 0
Oklahoma
Country [30] 0 0
United States of America
State/province [30] 0 0
Oregon
Country [31] 0 0
United States of America
State/province [31] 0 0
Pennsylvania
Country [32] 0 0
United States of America
State/province [32] 0 0
Rhode Island
Country [33] 0 0
United States of America
State/province [33] 0 0
South Carolina
Country [34] 0 0
United States of America
State/province [34] 0 0
Tennessee
Country [35] 0 0
United States of America
State/province [35] 0 0
Texas
Country [36] 0 0
United States of America
State/province [36] 0 0
Utah
Country [37] 0 0
United States of America
State/province [37] 0 0
Virginia
Country [38] 0 0
United States of America
State/province [38] 0 0
Washington
Country [39] 0 0
United States of America
State/province [39] 0 0
Wisconsin
Country [40] 0 0
Canada
State/province [40] 0 0
Alberta
Country [41] 0 0
Canada
State/province [41] 0 0
British Columbia
Country [42] 0 0
Canada
State/province [42] 0 0
Ontario
Country [43] 0 0
Canada
State/province [43] 0 0
Quebec
Country [44] 0 0
Puerto Rico
State/province [44] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Incyte Corporation
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Children's Oncology Group
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02723994
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Albert Assad, MD
Address 0 0
Incyte Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Incyte Corporation Call Center
Address 0 0
Country 0 0
Phone 0 0
1.855.463.3463
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02723994