Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors
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|ClinicalTrials.gov Identifier: NCT03610971|
Recruitment Status : Recruiting
First Posted : August 1, 2018
Last Update Posted : January 3, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Chronic Phase Chronic Myeloid Leukemia Chronic Myeloid Leukemia, Chronic Phase||Drug: Ruxolitinib Drug: BCR-ABL Tyrosine Kinase Inhibitor (TKI)||Phase 2|
All participants will have a confirmed diagnosis of chronic phase chronic myeloid leukemia (CML) and must have previously attempted to discontinue TKI therapy. All participants must be restarted on a TKI at the time of relapse in order to be eligible for this trial.
After completion of 12 cycles of combination therapy, eligible participants will remain in the TFR phase of the study for up to 36 months, and will have central polymerase chain reaction (PCR) testing during the first 24 months. Therefore, the total duration of the trial will be approximately 48 months (12 months on combination treatment phase + 36 months in the TFR phase).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||51 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors in Chronic Phase Chronic Myeloid Leukemia (CP-CML) Patients Who Relapsed After a Prior Attempt at TKI Discontinuation|
|Actual Study Start Date :||November 19, 2019|
|Estimated Primary Completion Date :||January 2024|
|Estimated Study Completion Date :||January 2024|
Experimental: Combination Therapy + Remission Phase
Combination therapy followed by treatment free remission (TFR) phase.
Combination Therapy: Ruxolitinib plus BCR-ABL Tyrosine Kinase Inhibitors (TKIs).
All eligible patients will begin ruxolitinib in combination with their BCR-ABL TKI on cycle 1 day 1 of the combination phase. For cycle 2 and beyond, if day 1 of a cycle is delayed, day 1 procedures should be repeated if out of the specified window and day 1 of the cycle is considered the day study drug is restarted. They will continue combination therapy for a total of 12 cycles. Each cycle will be approximately 28 days.
At the end of 12 cycles ruxolitinib will be discontinued and any patient who has met the criteria for the treatment free remission (TFR) screening phase will enter into the TFR phase. Once in the TFR phase, participants will discontinue their BCR-ABL TKI and be monitored off treatment.
Ruxolitinib: 15 mg by mouth (PO) twice a day (BID).
Other Name: Jakafi®
Drug: BCR-ABL Tyrosine Kinase Inhibitor (TKI)
The BCR-ABL TKIs that will be used include imatinib, dasatinib, nilotinib or bosutinib.
Other Name: TKI
- 12 Month Treatment Free Remission (TFR) [ Time Frame: 12 months ]TFR rate after completion of 12 cycles of combination therapy.
- Adverse Events Possibly Related to Study Treatment [ Time Frame: Up to 30 days post treatment, approximately 13 months per participant ]Establish the adverse event profile of ruxolitinib in combination with BCR-ABL TKIs: Adverse Events (AEs) and Serious Adverse Events (SAEs) according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0, that are possibly, probably, or definitely related to study treatment.
- Incidence of Improved Scores in Health Related Quality of Life Questionnaire [ Time Frame: Up to 48 months ]Number of participants with an improved score in 2 or more categories of the questionnaire at the end of the TFR phase, when compared to the score for the same questions when completed at the end of 12 cycles of combination therapy.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Willing and able to give informed consent
- Diagnosed with CML in chronic phase and have either the b3a2 (e14a2) or b2a2 (e13a2) variants that give rise to the p210 BCR-ABL protein.
- Must have a documented history of attempting only one prior TKI discontinuation under the guidance of a treating physician
Must have met ALL the following criteria prior to first attempt to discontinue their TKI:
- Stable molecular response (MR4; <0.01% IS) for > 2 years, as documented on at least 4 tests, performed at least 3 months apart
- Treatment with one of the following FDA approved TKI; imatinib, dasatinib, nilotinib or bosutinib, at any dose for a minimum of 3 years prior to discontinuing TKIs
- Has been on any number of TKIs, but has not been resistant to any TKI (changes made for intolerance are allowed)
- Must have relapsed (defined as loss of major molecular response (MMR), RQ-PCR for BCR-ABL > 0.1% IS after first attempted discontinuation of TKI
- After first failed TFR attempt, must have a minimum duration of 1 year on a TKI, and must plan to remain on this same TKI for a minimum of 12 months during the combination treatment phase
- Current TKI must be the same as the TKI being taken prior to the initial TFR attempt (e.g., if patient is on imatinib prior to first TFR attempt, they should be on imatinib at time of enrollment on this study)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-3
- Must have a RQ-PCR for BCR-ABL less than 0.01% IS reported by the trial designated central lab at time of study enrollment
- Must adhere to all study contraception guidelines
- History of accelerated or blast phase CML
- History of TKI resistance
- A second malignancy requiring active treatment
- Have previously received treatment with a JAK inhibitor.
- Platelet count less than 100 × 10^9/L or an absolute neutrophil count of less than 1 × 10^9/L or Hemoglobin less than 8 g/dL
- AST and ALT ≥ 3 times the institutional upper limit of normal (ULN)
- Creatinine ≥ 2 times ULN
- Total bilirubin ≥ 1.5 times ULN (unless direct bilirubin is within normal limits)
- Pregnant or lactating
- Unable to comply with lab appointments schedule and patient response outcome assessments
- Another investigational drug within 4 weeks of enrollment
- Any serious medical or psychiatric illness that could, in the investigator's opinion, interfere with the completion of treatment according to this protocol
- Have undergone a prior allogeneic transplant
- Screening 12-lead ECG showing a baseline corrected QT interval >500msec (patients with a pacemaker will still be eligible with QTc>500msec)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03610971
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute||Recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Christine Ternival 813-745-2146 Christine.Ternival@moffitt.org|
|Contact: Kendra Sweet, M.D. 813-745-8986 firstname.lastname@example.org|
|Principal Investigator: Kendra Sweet, M.D.|
|United States, Georgia|
|Emory -Winship Cancer Institute||Not yet recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Rebecca Klisovic, MD 404-778-1900 Rebecca.Klisovic@emoryhealthcare.org|
|Principal Investigator: Rebecca Klisovic, MD|
|United States, New Jersey|
|Memorial Sloan Kettering - Bergen||Recruiting|
|Montvale, New Jersey, United States, 07645|
|Contact: Michael Mauro, MD 646-608-3744 MauroM@mskcc.org|
|United States, New York|
|Roswell Park Comprehensive Cancer Center||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: James Thompson, MD 716-845-2300 James.Thompson@roswellpark.org|
|Principal Investigator: James Thompson, MD|
|David H. Koch Center for Cancer Care at Memorial Sloan Kettering||Recruiting|
|New York, New York, United States, 10021|
|Contact: Michael Mauro, MD 646-608-3744 MauroM@mskcc.org|
|United States, Oregon|
|Oregon Health & Science University||Recruiting|
|Portland, Oregon, United States, 97239|
|Contact: Michael Heinrich, MD 503-494-1080 email@example.com|
|United States, Washington|
|Fred Hutchinson Cancer Research Center||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Vivian Oehler, MD 206-667-1340 VOehler@u.washington.edu|
|Principal Investigator: Vivian Oehler, MD|
|United States, Wisconsin|
|Froedtert Hospital & the Medical College of Wisconsin||Recruiting|
|Milwaukee, Wisconsin, United States, 53226|
|Contact: Ehab Atallah, MD 414-805-4600 firstname.lastname@example.org|
|Principal Investigator: Ehab Atallah, MD|
|Principal Investigator:||Kendra Sweet, M.D.||H. Lee Moffitt Cancer Center and Research Institute|
|Responsible Party:||H. Lee Moffitt Cancer Center and Research Institute|
|Other Study ID Numbers:||
HJKC3-0002 ( Other Identifier: H. Jean Khoury Cure CML Consortium )
|First Posted:||August 1, 2018 Key Record Dates|
|Last Update Posted:||January 3, 2023|
|Last Verified:||December 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Chronic Myeloid Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Bone Marrow Diseases