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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by H. Lee Moffitt Cancer Center and Research Institute
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01702064
First received: October 3, 2012
Last updated: March 20, 2015
Last verified: March 2015
  Purpose

This study is designed to determine the maximal tolerated dose of Ruxolitinib in combination with nilotinib in patients with chronic myeloid leukemia (CML).


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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I 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. If 2 or more participants within a cohort experience a dose limiting toxicity (DLT), then the MTD will have been exceeded and the preceding dose level will be evaluated as the MTD. A minimum of 6 participants must be evaluated at the dose level in order for it to be declared as the MTD.

    Dose limiting toxicity is defined as:

    • Any non-hematological toxicity ≥ grade three, excluding any untreated nausea, vomiting, diarrhea or fatigue that occurs during the first 56 days of therapy.
    • Grade three thrombocytopenia with active bleeding or grade four thrombocytopenia or febrile neutropenia (ANC <500 cells/µL and fever > 101.0 F (38.5C)).
    • Any treatment related grade five toxicity (i.e., death).


Other Outcome Measures:
  • Complete Molecular Response Rate [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    Complete molecular response rate (CMR >4.5 log reduction) after the treatment combination.


Estimated Enrollment: 18
Study Start Date: February 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nilotinib with Ruxolitinib

The starting dose of ruxolitinib will be 5mg by mouth (PO) twice a day (BID) and will increase by 5 mg increments in each cohort, to a maximum dose of 15 mg PO BID. Nilotinib will be given at a dose ranging from 300 mg PO BID to 400 mg PO BID, depending on the participant's dose prior to enrollment on the trial.

Dose Level 1: Ruxolitinib 5 mg twice a day (BID); Nilotinib 300 mg or 400 mg BID.

Dose Level 2: Ruxolitinib 10 mg BID; Nilotinib 300 mg or 400 mg BID.

Dose Level 3: Ruxolitinib 15 mg BID; Nilotinib 300 mg or 400 mg BID.

Drug: Nilotinib

Participants 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.

Other Names:
  • Tasigna
  • BCR-ABL kinase inhibitor
Drug: Ruxolitinib
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

  Eligibility

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

Inclusion Criteria:

  • Must have chronic phase chronic myeloid leukemia (CML). They must also be under treatment with nilotinib as either first, second, or third-line therapy.
  • Must have a complete cytogenetic response (CCyR) OR must have been on nilotinib for a minimum of 6 months.
  • Must not have undergone treatment for any other form of cancer (aside from non-melanoma skin cancer) in the past 5 years.
  • 18 years of age or older and must be able to speak and read English or Spanish.
  • Able to provide informed consent.
  • Prior therapy with a tyrosine kinase inhibitor (TKI) other than nilotinib is allowable, however, nilotinib must be the current therapy. All participants must be under the care of a Moffitt Cancer Center physician, and enrollment is expected to be complete within 6 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%.
  • Must have normal organ and marrow function as defined in study protocol.
  • 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
  • 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.
  • 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.
  • 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 by mouth, twice a day (PO BID) or a lower dose are not eligible.
  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 ClinicalTrials.gov identifier: NCT01702064

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: William Prada    813-745-3323    william.prada@moffitt.org   
Principal Investigator: Kendra Sweet, M.D.         
Sub-Investigator: Javier Pinilla-Ibarz, M.D., Ph.D.         
Sub-Investigator: Rami Komrokji, M.D.         
Sub-Investigator: Timothy Kubal, M.D.         
Sub-Investigator: Jeffrey Lancet, M.D.         
Sub-Investigator: Alan List, M.D.         
Sub-Investigator: Bijal Shah, M.D.         
Sub-Investigator: Eric Padron, M.D.         
Sub-Investigator: Kenneth Zuckerman, M.D.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Incyte Corporation
Investigators
Principal Investigator: Kendra Sweet, M.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
ClinicalTrials.gov Identifier: NCT01702064     History of Changes
Other Study ID Numbers: MCC-17114
Study First Received: October 3, 2012
Last Updated: March 20, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
CML
CP-CML
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
Leukemia
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on March 26, 2015