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Ruxolitinib in Combination With Nilotinib in Chronic Myeloid Leukemia (CML) Patients

This study is ongoing, but not recruiting participants.
Incyte Corporation
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute Identifier:
First received: October 3, 2012
Last updated: December 9, 2014
Last verified: December 2014

The purpose of this study is to find out if treating Chronic Myeloid Leukemia (CML) with a combination of medications (one being therapy participants are already taking [nilotinib], along with a study drug [ruxolitinib]) can improve treatment of CML. The first step of the study is to learn the dose of ruxolitinib that is tolerable (bearable). It has already been studied in a number of patients with different bone marrow diseases and is approved for treatment of a disease called Myelofibrosis; however, it is not approved for treatment of CML or in combination with nilotinib. It is given orally (by mouth). Most people tolerate it well. Investigators hope to find out how well patients tolerate it when it is given along with nilotinib (Tasigna) for CML. Nilotinib is approved by the U.S. Food and Drug Association for the treatment of CML. Investigators will be testing different doses to determine how much of the medication people can tolerate (bear) before they develop side effects.

Condition Intervention Phase
Chronic Phase Chronic Myeloid Leukemia
Drug: Nilotinib
Drug: Ruxolitinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Ruxolitinib in Combination With Nilotinib in CML Patients With Evidence of Molecular Disease

Resource links provided by NLM:

Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Phase I: Maximum Tolerated Dose (MTD) [ Time Frame: Average of 6 months ] [ Designated as safety issue: Yes ]
    Maximum Tolerated Dose (MTD) of Ruxolitinib with Nilotinib. Dose escalation will follow a 3+3 study design.

  • Phase II: Complete Molecular Response (CMR) Rate [ Time Frame: Average of 6 months ] [ Designated as safety issue: No ]
    Complete Molecular Response (CMR): >4.5 log reduction in breakpoint cluster region-abelson (BCR-ABL) from diagnosis on the International Scale as measured by quantitative real-time polymerase chain reaction (RT-PCR). BCR-ABL is an abnormal gene found in most people with chronic myelogenous leukemia (CML) and in some people with acute lymphoblastic leukemia (ALL).

Secondary Outcome Measures:
  • Phase II: Duration of Treatment Response [ Time Frame: Average of 6 months ] [ Designated as safety issue: No ]
    To be assigned a status of CMR, changes in BCR-ABL levels must be confirmed by repeat assessments that should be performed 4 weeks after the criteria for response are first met. The duration of overall CMR is measured from the time measurement criteria are first met for CMR until the first date that recurrent disease is objectively documented.

Enrollment: 5
Study Start Date: February 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nilotinib with Ruxolitinib
Participants will continue to take nilotinib (Tasigna) the same way they have been taking it. They will also be given the study drug, ruxolitinib which will be taken by mouth every day as well. The dose of ruxolitinib participants get will depend on when they were enrolled in the study.
Drug: Nilotinib

In the phase I component of this study, patients will remain on the same dose of nilotinib they have been receiving prior to enrollment on the trial. This will range from 300 mg PO BID to 400 mg PO BID.

Dose modifications will not occur, as the purpose of this study is to determine the maximum tolerated dose of ruxolitinib, based on the number of dose limiting toxicities seen at a specific dose in combination with standard dose nilotinib.

Other Names:
  • Tasigna
  • BCR-ABL kinase inhibitor
Drug: Ruxolitinib
In the phase I component of this study, dose escalation will follow a 3+3 study design. Dose modifications will not occur, as the purpose of this study is to determine the maximum tolerated dose, based on the number of dose limiting toxicities seen at a specific dose.
Other Name: INCB018424


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • PHASE I: Patients must have chronic phase chronic myeloid leukemia (CML). They must also be under treatment with nilotinib as either first or second-line therapy.
  • PHASE II EXPANSION: Patients must have chronic phase CML and be undergoing treatment with first-line nilotinib for 6-18 months.
  • Must have a complete cytogenetic response (CCyR) OR must have been on nilotinib for a minimum of six months in order to be eligible for Phase I of this study. Must have at least a complete cytogenetic response (CCyR) AND have been on nilotinib for at least six months to be eligible for Phase II.
  • 18 years of age or older and must be able to speak and read English or Spanish
  • Must not have undergone treatment for any other form of cancer (aside from non-melanoma skin cancer) in the past 5 years
  • Must be able to provide informed consent
  • For the phase I component, prior therapy with a Tyrosine Kinase Inhibitor (TKI) other than nilotinib is allowable, however, nilotinib must be the current therapy. There are no restrictions as to how long patients received the alternate therapy, the dose of alternate therapy, or how long they have been receiving nilotinib, assuming they have achieved a CCyR. If patients have not achieved a CCyR, they must have been on nilotinib for a minimum of 6 months. All patients enrolled in this phase must be under the care of a Moffitt Cancer Center physician, and enrollment for this phase is expected to be complete within 6 months. The dose of nilotinib for patients receiving the drug in the second line setting due to failure of a first line TKI is generally 400 mg PO BID. In addition, if a patient is unable to tolerate second line nilotinib at 400 mg PO BID their dose may be decreased to 300 mg PO BID. In both instances they will be eligible for phase I.
  • For the phase II expansion, patients must not have received any TKI prior to nilotinib, and must have been under treatment with nilotinib for 6-18 months. Patients must have a complete cytogenetic response at the time of enrollment.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%
  • Patients must have normal organ and marrow function as defined below:

    • leukocytes ≥3,000/mL
    • absolute neutrophil count ≥1,500/mL
    • platelets ≥100,000/mL
    • total bilirubin within normal institutional limits
    • aspartic transaminase/alanine transaminase (AST/ALT) ≤2.5 X institutional upper limit of normal (ULN)
    • creatinine within normal institutional limits - OR -
    • creatinine clearance ≥60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of Ruxolitinib and nilotinib administration. Women of child-bearing age will be required to have a negative pregnancy test within 14 days of enrolling in this study.
  • Ability to understand and the willingness to sign a written informed consent document
  • Beta human chorionic gonadotrophin (B-HCG) will be performed on all women of child-bearing potential as screening prior to enrollment on this trial. STAT3 levels in the bone marrow will also be measured prior to enrollment.

Exclusion Criteria:

  • Patients who are in accelerated phase or blast phase CML
  • May not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib or other agents used in the study
  • Patients with a known history of a prolonged QT interval (QTc >480)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study. Women who are breast feeding their infants should discontinue this practice if the mother is treated with ruxolitinib.
  • Patient currently receiving any drugs considered to be strong CYP3A4 inducers or inhibitors which cannot be discontinued or changed to an alternative drug prior to enrolling on the trial
  • HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study.
  • Patients receiving nilotinib 200 mg PO BID are not eligible for phase I however they will be eligible for phase II.
  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 identifier: NCT01702064

United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Incyte Corporation
Principal Investigator: Javier Pinilla-Ibarz, M.D., Ph.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute Identifier: NCT01702064     History of Changes
Other Study ID Numbers: MCC-17114
Study First Received: October 3, 2012
Last Updated: December 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Chronic Phase-CML (CP-CML)
chronic myeloid leukemia

Additional relevant MeSH terms:
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Chronic-Phase
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms by Histologic Type processed this record on March 03, 2015