Taking part in a clinical trial may be the best treatment choice for some chronic myeloid leukemia (CML) patients. Clinical trials are under way for patients at every treatment stage and for patients in remission. Today's standard treatments for cancer are based on earlier clinical trials. The Leukemia & Lymphoma Society continues to invest funds in ALL research.
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Current CML Research and Clinical Trials
There are clinical trials for newly diagnosed patients, patients with advanced phase disease or patients who are either intolerant of, or resistant to, their current treatment. In light of the success of TKI therapy in treating most chronic phase CML patients, ongoing research studies are largely aimed at assessing whether patients with a stable complete molecular response can safely discontinue treatment, or if it is possible to add agents that help eradicate the few residual CML cells that presumably persist in all patients in remission.
The following approaches are under study in clinical trials for the treatment of patients with CML.
Drug Therapy. Bafetinib is a dual BCR-ABL and LYN kinase inhibitor, developed as a third-line treatment for patients with CML and certain forms of acute lymphoblastic leukemia. It is currently being studied in clinical trials where it is showing promising results in patients with Ph+ CML and other Ph+ leukemias that are either intolerant of, or resistant to, Gleevec and second-line therapies.
TKI Discontinuation Studies. Several studies are evaluating the ability of patients with a stable complete molecular response to interrupt TKI therapy and experience a treatment-free remission. These studies may eventually lead to improved confidence in the potential long-term safety of this approach, but at the present time, treatment discontinuation should not be pursued outside the context of a clinical trial.
Disease Eradication Strategies. Many lab studies have found potential treatments that may help eradicate the few remaining CML cells in most patients treated with TKIs, and hopefully cure patients so that they may discontinue medical therapies altogether. One area involves inhibitors of a protein called “smoothened” (SMO) in combination with BCR-ABL TKIs. A number of additional pathways are being studied, and efforts to assess their importance in CML patients are ongoing. Given that chronic phase CML is generally a slowly progressive disease, even in the absence of effective therapy, it will likely be many years before it is known whether strategies aimed at disease eradication truly achieve disease cure.
Vaccine Therapy. Various forms of vaccine therapy are being studied. Proteins on the surface of CML cells may be well-suited targets for such vaccines, which could employ a patient’s immune cells to attack his or her own CML cells. See the free LLS publication Immunotherapy Facts for information about the development of blood cancer vaccines.
Reduced-intensity Stem Cell Transplantation. A modified form of allogeneic transplantation called “reduced-intensity” or “nonmyeloablative” allogeneic stem cell transplantation may be an option for CML patients who do not respond to other treatments. Patients being prepared for a reduced-intensity transplant receive lower dosages of chemotherapy drugs and/or radiation in preparation for the transplant, compared to the dosages given to patients receiving an allogeneic transplant. Immunosuppressive drugs are used to prevent rejection of the donor stem cells. The engraftment of donor immune cells may allow these cells to attack the patient’s CML cells (a result called “graft-versus-tumor effect”). The theory being tested with a reduced-intensity transplant is that by undergoing less-toxic procedures prior to the transplant, the body is better able to withstand the transplant. However, full donor engraftment would still take place, and the desired graft-versus-tumor effect would still occur.
Other drugs are being tested in clinical trials to enhance the graft-versus-tumor effect of stem cell transplantation and to reduce the risks of graft-versus-host disease.
In addition, research is under way evaluating the use of umbilical cord blood as a source of stem cells for transplantation in children and adults. Cord blood provides another potential source of matched, unrelated stem cells for patients who do not have a matched, related stem cell donor. Results from cord-blood stem cell transplants have been promising, and there appears to be a reduced risk of acute graft-versus-host disease in younger cord-blood transplant patients. For more information about all types of stem cell transplantation, see the free LLS publication, Blood and Marrow Stem Cell Transplantation.