Ruxolitinib for Chronic Myeloid Leukemia (CML) With Minimal Residual Disease (MRD)
This is a two (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 Tyrosine Kinase Inhibitors (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
Hide Detailed Description
Study Drug Administration:
If you are found to be eligible to take part in this study, you will continue receiving the same TKI at the dose you had been receiving for the last 6 months.
You will also receive ruxolitinib by mouth 1 or 2 times daily. The dose level and how often you take the drug will depend on when you enter the study. The study staff will give you more detailed instructions about how often you will take the drug and what you should do if you vomit or miss a dose of study drug.
In the first part of the study, you will be assigned to a dose level of ruxolitinib based on when you join this study. Up to 3 dose levels of ruxolitinib will be tested. At least 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of ruxolitinib is found. This is called the Dose Escalation Group.
After the highest tolerated dose has been found, an extra 30 participants will receive ruxolitinib at that dose level. This is called the Dose Expansion Group.
Each study cycle is 4 weeks.
At every visit, you will be asked about any side effects you may have had and to list any drugs you may be taking.
Every 1-2 weeks for 8 weeks, then every 3 months, blood (about 2 teaspoons) will be drawn for routine tests and to test your kidney and liver function.
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.
Every 3-6 months for the first year, then every 6-12 months after that you will have a bone marrow aspirate to check the status of the disease.
At Weeks 1 (+/- 3 days) and 4 (+/- 1 week), Months 3 and 6 (+/- 1 month), then every 6-12 months after that, you will have a complete physical exam.
Length of Study:
You may continue taking the study drug for up to 2 years as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after you have completed both the end-of-treatment and follow-up visits.
After your last dose of study drug, you will be called or you will come in to the clinic within 30 days and you will be asked about any side effects and/or symptoms you may be having. If you are contacted by phone, the call should last about 2-3 minutes.
If you end your participation on this study because the disease has gotten worse, blood (about 1 tablespoon) will be drawn for molecular testing every 4 weeks for the first 6 months after you stop study treatment, then every 6 months for the next year, then every 6 weeks after that.
This is an investigational study. TKIs are approved for the treatment of CML and are given as part of your standard of care, even if you do not participate in this study. Ruxolitinib is FDA approved and commercially available for the treatment of patients with myelofibrosis. The combination of these drugs to treat CML is investigational.
Up to 48 patients will take part in this study. All will be enrolled at The University of Texas (UT) MD Anderson Cancer Center (MDACC).
|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|