Ruxolitinib Combined With Ibrutinib in Chronic Lymphocytic Leukemia Patients
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02912754|
Recruitment Status : Not yet recruiting
First Posted : September 23, 2016
Last Update Posted : March 13, 2017
|Condition or disease||Intervention/treatment||Phase|
|Leukemia, Lymphocytic, Chronic, B-Cell||Drug: ruxolitinib Drug: ibrutinib||Phase 1 Phase 2|
Ibrutinib is an effective drug that can extend the lives of CLL patients but it is not curative as a single agent and may eventually select for more aggressive disease. Survival of CLL cells in the presence of Ibrutinib may be enabled by signals from the microenvironment where the leukemia cells originate. These signals are transmitted into the cells by Janus Kinases (JAKs) such as janus kinase 1 (JAK1) and janus kinase 2 (JAK2). According, JAK inhibitors may overcome the cytoprotective properties of the CLL microenvironment and help to improve outcomes with Ibrutinib.
The JAK2 inhibitor Ruxolitinib is licensed for use in myelofibrosis and polycythemia rubra vera and its toxicity and efficacy as a single agent in CLL has been studied in two previous clinical trials. As a single agent, Ruxolitinib was inferior to Ibrutinib. However, Ruxolitinib was shown to cooperate with Ibrutinib and increase killing of CLL cells in vitro. Based on these observations, it is hypothesized that Ruxolitinib will significantly improve the therapeutic efficacy of single-agent Ibrutinib.
This is a single center phase I/II trial to determine the efficacy and safety of ruxolitinib tablets in CLL patients being treated until progression with Ibrutinib and considered at risk to progress on the basis of persistent lymphocytosis and lymphadenopathy after 1 year of Ibrutinib or elevated beta-2-microglobulin (b2M) levels after 6 months of Ibrutinib. Ruxolitinib will be administered for 21 days of a 35-day cycle to be repeated 6 more times.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial of Ruxolitinib in Chronic Lymphocytic Leukemia Patients at Risk for Progression on Ibrutinib|
|Estimated Study Start Date :||March 2017|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||August 2019|
Experimental: Ibrutinib plus Ruxolitinib
Patients taking ibrutinib for relapsed CLL will add ruxolitinib twice per day at the dose identified in a preliminary phase I trial for 7 cycles (3 weeks on/2 weeks off).
ruxolitinib will be added to ibrutinib or 3 out of 5 weeks per cycle
Other Name: jakafi
patients will be taking ibrutinib for at least 6 months and will continue to take it at the same dose and schedule while taking ruxolitinib
Other Name: imbruvica
No Intervention: Ibrutinib alone
Patients will continue to take Ibrutinib for the equivalent period of time.
- maximum tolerated dose (MTD) of ruxolitinib in combination with Ibrutinib. [ Time Frame: 2 years ]identify the MTD of ruxolitinib with ibrutinib
- ability of Ruxolitinib to increase the depth of response to Ibrutinib [ Time Frame: 2 years ]identify the number of complete responses that occur when ruxolitinib is added to ibrutinib
- effect of Ruxolitinib on levels of plasma cytokines and chemokines [ Time Frame: 3 years ]quantification of plasma cytokines and chemokines
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): NCT02912754
|Sunnybrook Odette Cancer Center||Not yet recruiting|
|Toronto, Ontario, Canada, M4N 3M5|
|Contact: Geetha Geetha Yogendran, BSc 416-480-5000 ext 89565 email@example.com|
|Contact: Lindsay McCaw, MSc 416-480-6100 ext 4244 firstname.lastname@example.org|
|Principal Investigator: david e spaner, MD|
|Sunnybrook Odette Cancer Center|
|Toronto, Ontario, Canada, M4N3M5|
|Principal Investigator:||David E Spaner, MD||Sunnybrook Odette Cancer Center|