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Ruxolitinib for Chronic Myeloid Leukemia (CML) With Minimal Residual Disease (MRD)

Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Leukemia

Intervention: Ruxolitinib (Drug); TKI (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Jorge Cortes, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

Overall contact:
Jorge Cortes, MD, Phone: 713-794-5783

Summary

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.

Clinical Details

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

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Maximum Tolerated Dose (MTD) for Ruxolitinib and Tyrosine Kinase Inhibitors (TKIs).

Secondary outcome: Clinical Activity of Ruxolitinib and Tyrosine Kinase Inhibitor (TKI)

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. Study Visits: 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 at Month 3 (+/- 3 weeks) and every 3 months after that, blood (about 2 teaspoons) will be drawn for routine tests and to test your kidney and liver function. Every month for the first 3 months, then every 3-6 months for the first year, then every 6-12 months 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. If the study doctor decides that this is in your best interest, you may be able to stop taking the study drug and/or your TKI. If you stop the study drug and/or TKI, every 4 weeks for the first 6 months after you stop treatment, then every 3 months for the next 12 months, and then every 6 months after that , blood (about 1 tablespoon) will be drawn for molecular testing. Your doctor will discuss this with you. 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. End-of-Treatment 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. Other Information: If necessary, some of these tests may be done by your home physician and the results faxed to MD Anderson for review. If you have severe side effects from the study drug, the study doctor may decide to reduce and/or stop drug dosing until your side effects improve. If the doctor thinks it is in you best interest, your dose may be increased. If all tests to find the disease are completely negative, you may have the option to stop both the TKI and ruxolitinib. If this happens, your doctor will monitor you closely to check for any evidence the disease has returned. If this is the case, treatment with one or both drugs may be re-started at the same doses you were taking before you stopped. 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 MD Anderson.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Patients 18 years or older with Philadelphia chromosome (Ph)-positive or BCR/ABL-positive CML (as determined by cytogenetics, FISH, or PCR). 2. Patients must be on continuous TKI therapy for management of their CML. Any commercially available and FDA- approved TKI can be used, i. e., imatinib mesylate (IM), nilotinib (NIL) or dasatinib (DAS). Patients may be receiving TKI at entry in the frontline or salvage setting, including patients currently on imatinib after alpha-interferon failure or on dasatinib or nilotinib after failure to prior therapy including imatinib. 3. Patients must have received the current TKI for at least 18 months and not have increased their dose in the last 6 months. 4. For the phase I portion of the study, patients may be included without a CCyR provided they remain in chronic or accelerated phase CML and have at least a CHR. For the Phase II portion of the study patients must be in complete cytogenetic remission (CCyR), regardless of the stage of disease they had at the time they started therapy with TKI. 5. Patients must have detectable BCR-ABL transcript levels meeting at least 1 of the following criteria: Patient has never achieved a major molecular response (MMR, as defined by a BCR-ABL/ABL /=1 x10(9)/L and platelets >/=100 x10(9)/L. 11. Serum creatinine < 1. 5 mg/dL or creatinine clearance greater or equal than 60 cc/min as defined by the Cockcroft-Gault Equation: Males(mL/min):(140-age)*IBW(kg) / 72*(serum creatinine (mg/dl)); Females (mL/min):0. 85*(140-age)*IBW(kg) / 72*(serum creatinine (mg/dl)). 12. Women of childbearing potential should be advised to avoid becoming pregnant while on therapy with Ruxolitinib and for 30 days after the last dose and practice effective methods of contraception. Men should be advised not to father a child while receiving treatment with Ruxolitinib and for 30 days after the last dose. Effective methods of contraception for this study include barrier methods (e. g., condoms, diaphragm); spermicidal jelly or foam; oral, depo provera, or injectable hormonal contraceptives; intrauterine devices; tubal ligation; and abstinence. Exclusion Criteria: 1. For the phase I portion of the study, patients in blast phase. For the phase II portion of the study, patients in accelerated or blast phase. 2. Patients receiving any other investigational agents. 3. Patients who are pregnant or breast-feeding. 4. Patients with clinically significant heart disease (NYHA Class III or IV). 5. Patients with QTc > 480 msec. 6. Patients taking a potent CYP3A4 inhibitor that cannot be changed to an alternate drug. 7. Known or suspected hypersensitivity to ruxolitinib. 8. Patients with advanced malignant hepatic tumors. 9. Patients with known active hepatitis B or C, or HIV infection. 10. Patients with other medical conditions or concomitant medications that in the opinion of the principal investigator may interfere with the therapeutic treatment.

Locations and Contacts

Jorge Cortes, MD, Phone: 713-794-5783

University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Additional Information

University of Texas MD Anderson Cancer Center Website

Starting date: July 2013
Last updated: July 17, 2015

Page last updated: August 23, 2015

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