| Eligibility |
Inclusion Criteria:
1. Patients must have Chronic Myeloid Leukemia in any phase (CP, AP, or BP of any
phenotype) or Ph+ Acute Lymphoblasic Leukemia. The confirmation of Ph+ chromosome can
be substituted by the presence of BCR/ABL transcript by PCR test at diagnosis.
2. Patients must be previously treated with and resistant, or intolerant, to 2 or more
lines of treatment including imatinib, dasatinib, or other investigational agent.
Patient who have CML-CP who were previously treated with and resistant to only
dasatinib are also included. At least 2 weeks must have elapsed from the last date of
treatment to the first dose of study treatment. Patients who have received Nilotinib
for more than 4 consecutive weeks will be excluded.
3. Must be =18 years old.
4. Provide written informed consent.
5. Eastern Cooperative Oncology Group (ECOG) performance status = 2.
6. Minimum life expectancy of 3 months or more.
7. Adequate organ liver and renal functions:
- Total bilirubin = 1.5 x ULN. Does not apply to patients with isolated
hyperbilirubinemia (e.g., Gilbert's Disease) of grade < 3;
- Alanine aminotransferase (ALT) = 2.5x ULN or or = 5.0 x ULN if considered due to
leukemia.
- Creatinine = 2.5 mg/dL.
- Alkaline phosphatase = 2.5 x ULN unless considered due to leukemia;
- Serum lipase and amylase = 1.5 x ULN
8. Normal serum levels = LLN (lower limit of normal) or corrected to within normal limits
with supplements, prior to the first dose of study medication, of potassium, magnesium
and calcium;
9. Female patients of childbearing potential must agree to use dual methods of
contraception and have a negative serum pregnancy test within 2 weeks prior to
enrollment. Male patients must use an effective barrier method of contraception if
sexually active with a female of child-bearing potential. Acceptable methods of
contraception are condoms, contraceptive patch, intrauterine device, diaphragm with
spermicidal gel, or a sexual partner who is surgically sterilized or post menopausal.
Post menopausal is defined as at least 12 consecutive months without menses.
10. Ability and willingness to comply with study procedures and schedule, in the
Investigator's opinion.
Exclusion Criteria:
1. Received Tyrosine Kinase Inhibitor therapy within 7 days prior to receiving the first
dose of Ruxolitinib+Nilotinib, with the exception of patients who have previously
received Nilotinib who must have stopped Nilotinib 4 weeks prior to receiving the
first dose of Ruxolitinib+Nilotinib.
Patients who have not recovered (> grade 1 by NCI CTCAE, v. 4.03) from AEs (except
alopecia) due to agents previously administered.
2. Patients who received other therapies as follows:
- For CP and AP patients:
Received any of the following within 2 weeks prior to receiving first dose of
Ruxolitinib + Nilotinib:
- Hydroxyurea (within 7 days of first dose)
- anagrelide
- interferon
- cytarabine
- immunotherapy
- any other cytotoxic chemotherapy, radiotherapy, or investigational therapy
- For BP patients:
Received any of the following within 2 weeks prior to receiving first dose of
Ruxolitinib + Nilotinib:
- chemotherapy other than hydroxyurea
- anagrelide
- interferon
- cytarabine
- immunotherapy
- any other cytotoxic chemotherapy, radiotherapy, or investigational therapy
- For Ph+ ALL patients:
Received any of the following within 2 weeks prior to the first dose of
Ruxolitinib+Nilotinib:
- corticosteroids
- vincristine
- Hydroxyurea (within 7 days of first dose)
- anagrelide
- interferon
- cytarabine
- immunotherapy
- any other cytotoxic chemotherapy, radiotherapy, or investigational therapy
3. Underwent autologous or allogeneic stem cell transplant within 60 days prior to
receiving the first dose of Ruxolitinib+Nilotinib; any evidence of on-going graft
versus-host disease (GVHD), or GVHD requiring immunosuppressive therapy.
4. Patients with any of the following:
Have prolonged QT (QTc >450 ms) or take medications that are known to be associated
with Torsades de Pointes, or potentially prolonging QT.
Long QT syndrome or familiar history of long QT syndrome Persistent significant
bradicardia (<50bpm) Experienced a myocardial infarction within 12 months of
registration
5. Require concurrent treatment with immunosuppressive agents, other than corticosteroids
prescribed for a short course of therapy.
6. Have previously been treated with Ruxolitinib.
7. Patients with CML CP are excluded if they are in MCyR.
8. Patients with CML AP, CML BP, or Ph+ ALL are excluded if they are in MCyR.
9. Have active central nervous system (CNS) disease as evidenced by cytology or
pathology. History itself of CNS involvement is not exclusionary if CNS has been
cleared with a documented negative lumbar puncture. In the absence of clinical CNS
disease, lumbar puncture is not required.
10. Have significant or active cardiovascular disease or significant bleeding disorder
unrelated to CML or Ph+ ALL.
11. Have a history of pancreatitis or alcohol abuse.
12. Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL).
13. Have malabsorption syndrome or other gastrointestinal illness that could affect the
absorption of the study drug.
14. Patients with inadequate bone marrow reserve within 2 weeks prior to start study drug
as demonstrated by:
- Absolute neutrophil count (ANC) that is = 1000/µL.
- Platelet count that is < 125,000/µL without the assistance of growth factors,
thrombopoietic factors or platelet transfusions.
15. Patients with any history of platelet counts < 50,000/µL or ANC < 500/µL except during
treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for
any other reason.
16. Patients with coagulation parameters (PT, PTT, INR) = 1.5 ULN within 2 weeks prior to
starting study drug.
17. Developed the T315I, T315A Y253H, E255K/V or F359C/V mutation after any TKI therapy.
18. Patients with HLA matched donor and eligible for allogeneic transplantation for CML
treatment.
19. Patient being treated concurrently with any of the following prohibited medications:
- JAK inhibitor
- Any investigational medication other than the study drugs. Use of such
medications within 14 days or 6 half-lives, whichever is longer, prior to the
first dose of study drug is prohibited
- Potent inducers and inhibitors of CYP3A4• Use of HU, interferon, thalidomide,
busulfan, lenalidomide, anagrelide, is not permitted at any time beginning 28
days prior to the first Baseline assessment.
- Hematopoietic growth factor receptor agonists (eg, erythropoietin (Epo),
granulocyte colony stimulating factor (GCSF), romiplostim, eltrombopag) must not
be used as they may be associated with spleen size increases. Growth factors must
not have been used for at least one month prior to receiving the first dose of
study drug.
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