Chronic myelogenous leukemia is a hot area of medical research, in part because of the development of the first effective treatment (Gleevec) a decade ago and the insights about the biology of the disease that have resulted from that important discovery.
Over one thousand studies are currently ongoing in CML, according to the registry maintained by the U.S. National Institutes of Health (see clinicaltrials.gov). At the time of writing, seven studies on CML treatments are recruiting in Canada. Here’s a summary of what they are investigating.
Treatment-free remission: Studies to date have indicated that many people who achieve a deep molecular response (defined as 4-log reduction in BCR-ABL transcripts [MR4.0] or better [MR4.5 or MR5.0]) and sustain this treatment effect for two or more years may be able to stop treatment altogether. CML isn’t necessarily cured – leukemia cells can persist in the bone marrow – but the disease is well enough suppressed that a person can try going off their medication. It’s important to state that stopping treatment should not be done on your own. The frequent testing and close supervision of a clinical trial are needed to ensure that CML doesn’t make a comeback.
DASFREE is a phase II trial that is now recruiting people who have been taking Sprycel for at least two years and have maintained a deep molecular response (MR4.5) for at least one year. The study is recruiting in Toronto, as well as in the U.S. (7 centres), France (4 centres), Germany (5 centres), Italy (6 centres) and Spain (4 centres).
A second study, called TRAD (for Treatment-free Remission Accomplished With Dasatinib in Patients With CML) is for people who have been taking Gleevec for at least three years and have achieved a deep molecular response (MR4.5 or better). If a person loses their molecular response off treatment, they will be required to start on Sprycel. The study is being run at 10 Canadian centres: four in Ontario, three in Quebec, and one centre each in Nova Scotia, Alberta and Manitoba.
Comparing treatments: A large phase III study is comparing the safety and effectiveness of Tasigna versus Gleevec in people newly-diagnosed with CML. Close to 200 sites are participating in countries such as the U.S., Mexico, U.K., Belgium, Netherlands, France, Germany, Italy, Spain, Austria, Switzerland, Sweden, Denmark, Norway, Czech Republic, Poland, Russian Federation, Turkey, Brazil, Argentina, Columbia, Venezuela, Egypt, Japan, Korea, Malaysia, Singapore, Thailand, and South Africa. There are six participating centres in Quebec, Ontario and B.C.
The DASCERN study will compare Sprycel with Gleevec in people who haven’t responded adequately to front-line Gleevec. The study is running in the U.S., Belgium, France, Italy, Spain, Austria, Czech Republic, Poland, Brazil, Argentina, China, Korea, and Thailand. One centre in New Brunswick is also participating.
Long-term study: Extension studies are add-ons to clinical trials to enable ongoing evaluation of a drug’s safety and effectiveness. People who have participated in clinical trials of Bosulif can continue in an extension study. Over 100 sites are involved in over 20 countries, including the U.S., U.K., Australia, China, Singapore, Japan, Korea, Thailand, Argentina, Brazil, Chile, Peru, Columbia, Belgium, Netherlands, France, Italy, Spain, Hungary, Finland, Latvia, Poland, Ukraine, Russian Federation, Turkey, South Africa, and India. There are 10 Canadian centres in Ontario, Quebec, Alberta and B.C.
Combination therapies: TKIs are highly effective in treating CML, but they have a couple of limitations. A minority of people can develop drug-resistant mutations, so treatment loses its effectiveness. In addition, TKIs don’t kill the source – leukemic cells residing in the bone marrow. So adjunctive therapies are being investigated that may make TKIs more effective.
A phase I/II study is looking at the combination of Tasigna and Jakavi (or Jakafi; ruxolitinib) in people with resistance to treatment. TKIs block the signals that cause white blood cells to proliferate; Jakavi also blocks abnormal signalling but by a different “channel”. Jakavi is already approved for the treatment of other blood cancers. The first part of the study (phase I) will test different doses; the second part (phase II) will determine the safety and effectiveness of the combination. The study is open to people with chronic-phase or progressive CML who are resistant to prior therapies. Subjects are being recruited at one centre in Ontario.
A second study is investigating the combination of Sprycel and Opdivo (nivolumab), a drug that is given by infusion (a slow drip into the vein). Opdivo targets a protein that inhibits the immune system from killing cancer cells, which frees immune cells to do their job. Opdivo is an approved treatment for melanoma and lung cancer. Subjects are being recruited at three centres in Ontario, Quebec and Nova Scotia.
Participating in a clinical trial may be an option for some people, depending on their circumstances. Your hematologist can provide you with information about any trials running in your area.