Ruxolitinib in Combination With Nilotinib in Chronic Myeloid Leukemia (CML) Patients
Chronic Phase Chronic Myeloid Leukemia
|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|
- 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).
- 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.
|Study Start Date:||February 2013|
|Estimated Study Completion Date:||April 2017|
|Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
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.
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: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
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:||Kendra Sweet, M.D.||H. Lee Moffitt Cancer Center and Research Institute|