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.
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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 tyrosine kinase (BTK). Examples of kinase inhibitor therapy include
- ACP-196. ACP-196 is an orally administered BTK inhibitor. This drug is in clinical trials for CLL patients. These patients have reached remission taking ACP-196 alone. The side-effect profile has been good. This drug, like ibrutinib, does cause temporary lymphocytosis (high lymphocyte count) when given by itself but this has not been shown to have any significant clinical consequence. There are other BTK inhibitors also in clinical trials at this time.
- Duvelisib (IPI-145). Duvelisib is an orally administered PI3-kinase inhibitor. It is currently in phase 3 clinical trials for CLL where significant durable remissions have been observed. Clinical trials are now combining this with other therapeutics in CLL. 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. It has many of the same side effects as idelalisib.
- ABT-199. ABT is a B cell CLL/lymphoma 2 (BCL-2) 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 that is refractory to fludarabine. It is very active in CLL and currently is being tested in phase 3 clinical trials.
- Dinaciclib. Dinaciclib is a second-generation cyclin-dependent kinase (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..
MOR208 is an antibody that targets CD19 on the surface of CLL cells. It is being studied in phase 1/2 clinical trials in CLL and in combination with other therapies such as lenalidomide. Antibodies and antibody-like molecules (otlertuzumab) are also being developed clinically at this time.
Lenalidomide (Revlimid®) is a targeted 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 3 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. Other studies include Revlimid with Rituxan® or Arzerra®; Revlimid, fludarabine and Rituxan combined for minimally treated and untreated CLL patients; and Revlimid and ibrutinib 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. Other targeted molecules (CC-122) similar to lenalidomide are beginning clinical development in CLL.
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.