Ruxolitinib in Combination With Nilotinib in Chronic Myeloid Leukemia (CML) Patients
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.
Chronic Phase Chronic Myeloid Leukemia
|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|
- 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).
- 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.
|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)|
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.
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: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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01702064
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Javier Pinilla-Ibarz, M.D., Ph.D.||H. Lee Moffitt Cancer Center and Research Institute|