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.
Brief Title
A Phase 2 Study of Ruxolitinib With Chemotherapy in Children With Acute Lymphoblastic Leukemia
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Leukemia
Eligibility Criteria
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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Keywords
B-cell acute lymphoblastic leukemia (ALL)
pediatric
multi-agent chemotherapy
JAK inhibitor
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
21 Years
Minimum Age
1 Year
NCT Id
NCT02723994
Org Class
Industry
Org Full Name
Incyte Corporation
Org Study Id
INCB 18424-269
Overall Status
Active, not recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Measure
Part 1: Safety/tolerability of ruxolitinib in combination with chemotherapy as measured by adverse events (AEs), vital signs, clinical laboratory tests, and echocardiograms
Outcome 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)
Outcome Measure
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
Outcome Time Frame
Part 2: assessed at 3 years
Secondary Ids
Secondary Id
AALL1521
Secondary Outcomes
Outcome 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)
Outcome Measure
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
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Maximum Age Number (converted to Years and rounded down)
21
Minimum Age Number (converted to Years and rounded down)
1
Investigators
Investigator Type
Principal Investigator
Investigator Name
Lisa Gennarini
Investigator Email
lfigueir@montefiore.org
Investigator Phone
Categories Mesh Debug
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Cancer --- NEOPLASMS
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
Blood & Bone Marrow Cancers --- LEUKEMIA, LYMPHOID
Blood & Bone Marrow Cancers --- LYMPHOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- LYMPHATIC DISEASES
Blood & Bone Marrow Cancers --- IMMUNOPROLIFERATIVE DISORDERS
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
MeSH Terms
LEUKEMIA
PRECURSOR B-CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
LEUKEMIA, LYMPHOID
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
IMMUNE SYSTEM DISEASES
RUXOLITINIB
ASPARAGINASE ERWINIA CHRYSANTHEMI RECOMBINANT
CYCLOPHOSPHAMIDE
CYTARABINE
DEXAMETHASONE
DOXORUBICIN
LEVOLEUCOVORIN
MERCAPTOPURINE
METHOTREXATE
PEGASPARGASE
PREDNISONE
THIOGUANINE
VINCRISTINE
PHOSPHORAMIDE MUSTARDS
NITROGEN MUSTARD COMPOUNDS
MUSTARD COMPOUNDS
HYDROCARBONS, HALOGENATED
HYDROCARBONS
ORGANIC CHEMICALS
PHOSPHORAMIDES
ORGANOPHOSPHORUS COMPOUNDS
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
ARABINONUCLEOSIDES
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES
PREGNADIENETRIOLS
PREGNADIENES
PREGNANES
STEROIDS
FUSED-RING COMPOUNDS
POLYCYCLIC COMPOUNDS
STEROIDS, FLUORINATED
DAUNORUBICIN
ANTHRACYCLINES
NAPHTHACENES
POLYCYCLIC AROMATIC HYDROCARBONS
HYDROCARBONS, AROMATIC
HYDROCARBONS, CYCLIC
AMINOGLYCOSIDES
GLYCOSIDES
CARBOHYDRATES
LEUCOVORIN
FORMYLTETRAHYDROFOLATES
TETRAHYDROFOLATES
FOLIC ACID
PTERINS
PTERIDINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
SULFHYDRYL COMPOUNDS
SULFUR COMPOUNDS
PURINES
AMINOPTERIN
PREGNADIENEDIOLS
VINCA ALKALOIDS
SECOLOGANIN TRYPTAMINE ALKALOIDS
INDOLE ALKALOIDS
ALKALOIDS
INDOLES
INDOLIZIDINES
INDOLIZINES