Ruxolitinib for Chronic Myeloid Leukemia (CML) With Minimal Residual Disease (MRD)
This is a 2 part study. The goal of the first part of this clinical research study is to find the highest tolerable dose of ruxolitinib that can be given with a TKI that you are already taking (such as gleevec, sprycel, or nilotinib) as part of your standard of care treatment. The goal of the second part of this study is to learn if this drug combination can help to control CML. Although you have a good response to therapy, the disease is still detectable at low levels (this is called "minimal residual disease"). Researchers believe that eliminating all detectable evidence of disease may decrease the chances that the leukemia will ever come back. The safety of the drug combination will also be studied in both parts.
Ruxolitinib is designed to block a protein called Jak2 that may help keep some leukemia cells alive even with TKI therapy. Blocking this protein may cause the cells to die.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I-II Study of Ruxolitinib (INCB18424) for Patients With Chronic Myeloid Leukemia (CML) With Minimal Residual Disease While on Therapy With Tyrosine Kinase Inhibitors|
- Maximum Tolerated Dose (MTD) for Ruxolitinib and Tyrosine Kinase Inhibitors (TKIs). [ Time Frame: 12 months from start of therapy ] [ Designated as safety issue: Yes ]MTD is highest dose level at which 6 patients were treated and at most 1 patient experienced a dose limiting toxicity (DLT). Non-hematologic DLT defined as grade 3 or 4 elevation of ALT or AST possibly related to tyrosine kinase inhibitor (TKI). Hematologic DLT defined as grade 4 neutropenia, anemia, and/or thrombocytopenia lasting for 4 weeks or more.
- Clinical Activity of Ruxolitinib and Tyrosine Kinase Inhibitor (TKI) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Primary endpoint to determine if residual disease as measured by PCR can decrease by at least 1 log or become undetectable within 12 months from the start of study therapy. Progression defined as confirmed loss of complete cytogenetic response (CCyR) for patients who enter study with this response. "Confirmed" is defined here as assessed in two consecutive cytogenetic analyses separated by at least a month. Before each cycle for the first 3 cycles, then every 3-6 cycles for the first year, then every 6-12 cycles after that, blood (about 1 tablespoon) drawn for molecular testing.
|Study Start Date:||July 2013|
|Estimated Primary Completion Date:||July 2019 (Final data collection date for primary outcome measure)|
Experimental: Ruxolitinib + TKI
Phase I Dose Escalation Group: Ruxolitinib starting dose level 5 mg orally, twice daily. Patients continue receiving commercially available TKIs (IM, NIL or DAS) at dose they had been receiving during the last 6 months.
Phase II Dose Expansion Group: Ruxolitinib starting dose level MTD from Phase I Dose Escalation Group. Patients continue receiving commercially available TKIs (IM, NIL or DAS) at dose they had been receiving during the last 6 months.
Once MTD is defined for imatinib in the phase I portion of the study the phase 2 portion of the study will start with imatinib only. The phase I portion of the study with dasatinib and nilotinib will open once MTD is defined for the imatinib-based combination.
Phase I Dose Escalation Group: Ruxolitinib starting dose level 5 mg orally, twice daily.
Phase II Dose Expansion Group: Ruxolitinib starting dose level MTD from Phase I.
Other Names:Drug: TKI
Phase I Dose Escalation Group and Phase II Dose Expansion Group: Patients continue receiving commercially available TKIs (IM, NIL or DAS) at dose they had been receiving during the last 6 months.
Other Name: Tyrosine kinase inhibitor
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01751425
|Contact: Jorge Cortes, MD||713-794-5783|
|United States, Texas|
|UT MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jorge Cortes, MD||UT MD Anderson Cancer Center|