Taking part in a clinical trial may be the best treatment choice for some chronic lymphocytic leukemia (CLL) patients. Clinical trials are under way to improve remission rates for CLL. Today's standard treatments for cancer are based on earlier clinical trials. The Leukemia & Lymphoma Society continues to invest funds in CLL research.
Clinical trials can involve new drugs, new combinations of drugs or approved drugs being studied to treat patients in new ways such as new drug doses or new schedules to administer the drugs. Clinical trials are conducted worldwide under rigorous guidelines to help doctors find out whether new cancer treatments are safe and effective or better than the standard treatment.
Current CLL Research and Clinical Trials
Below are some of the types of research and trials for new or improved drug therapies under way:
Kinase Inhibitor Therapy
Kinases are enzymes that are found in both normal cells and cancer cells. Some cancer cells can be targeted by kinase inhibitor drugs that destroy the cancer cells. Kinase inhibitor drugs may be associated with fewer side effects than some other chemotherapy agents. There are many different kinases in CLL cells, including a phosphatidylinositol 3-kinase (PI3-kinase) and Bruton's tyrosine kinase (BTK).
Examples of kinase inhibitor therapy include
- PCI-32765. PCI-32765 is an orally administered BTK inhibitor that is in phase II clinical trials for CLL where significant durable remissions have been observed with single agent activity and it has shown a very favorable side-effect profile. Efforts to combine PCI-32765 with other agents such as bendamustine (Treanda®) or ofatumumab (Arzerra®) are ongoing. Phase III studies are being planned for this agent. This agent does cause temporary lymphocytosis (high lymphocyte count) when given by itself but this has not been shown to have any significant clinical consequence.
- GS-1101 (CAL-101). GS-1101 is an orally administered PI3-kinase inhibitor that is in phase II clinical trials for CLL where significant durable remissions have been observed with single agent activity. Efforts to combine GS-1101 with other agents such as Treanda, rituximab (Rituxan®), or Arzerra are ongoing. Phase III studies are being planned for this agent. This agent also causes temporary lymphocytosis (high lymphocyte count) when given by itself but this has not been shown to have any significant clinical consequence.
- Flavopiridol. Flavopiridol is a CDK inhibitor being studied in people with high-risk genetic features whose CLL has responded to few, if any, standard treatments. It is being studied to treat CLL or prolymphocytic leukemia arising from CLL that is refractory to fludarabine.
- Dinaciclib. Dinaciclib is a second-generation CDK inhibitor being studied in patients with relapsed CLL who are not responsive to other therapies. It has shown activity in this group including patients with high-risk genetic features.
Xm5574 is an antibody that targets CD19 on the surface of CLL cells. It is being studied in phase I/II clinical trials in CLL.
Lenalidomide (Revlimid®) is an oral drug that is used to treat patients with myeloma. It stimulates a person's own immune system to attack cancer cells. This drug is being evaluated in several CLL trials, including a phase III study, to determine if Revlimid, given as a maintenance therapy, is safe and effective in further improving the quality and duration of the response to treatment. This study will compare the effects of Revlimid with the effects of a placebo. Revlimid is also being studied as a possible treatment for people with CLL following second-line therapy. Other studies include Revlimid with Rituxan or Arzerra; Revlimid, fludarabine and Rituxan combined for minimally treated and untreated CLL patients; and Revlimid, fludarabine and cyclophosphamide combined for patients with advanced-relapsed or refractory CLL. One problem that has emerged in patients with long-term (maintenance) use of Revlimid in multiple myeloma has been the occurrence of secondary cancers. The relevance of this finding to CLL is uncertain although the current trials with Revlimid are being monitored very carefully for this complication.
Allogeneic Stem Cell Transplantation
Experts are also studying allogeneic stem cell transplantation to specifically treat high-risk CLL patients in clinical trials. Doctors are already using them as an investigational treatment option. Meanwhile, experts are hoping to find ways to reduce a transplant's toxicity and make it a possible therapy for more people with CLL. Stem cell transplantations have a high risk of serious complications.
Reduced-Intensity Allogeneic Stem Cell Transplantation
Doctors are studying a reduced-intensity stem cell transplantation, also called a nonmyeloablative transplantation, that may help some CLL patients, such as those who are older and those who have poor overall health, better tolerate stem cell transplantation. Unlike standard transplantation, reduced-intensity transplantation doesn't completely destroy the patient's diseased marrow and relies on donor immune cells to fight the disease.