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. Some types of cancer can be treated by kinase inhibitor drugs that target specific enzymes in the cancer cells, which are involved in cell growth and death. These drugs may be associated with fewer side effects than traditional chemotherapy agents. An example of a kinase inhibitor therapy drug under study in clinical trials includes acalabrutinib (ACP-196). Acalabrutinib is a second-generation Bruton tyrosine kinase (BTK) inhibitor that is administered orally. This drug is being studied in clinical trials for relapsed/refractory CLL patients, including those with del(17p).​
• Monoclonal Antibodies.
  • ​Veltuzumab (IMMU-106). This anti-CD20 monoclonal antibody has shown promising results in CLL treatment for previously untreated patients and patients whose disease has relapsed.
  • Lucatumumab. This is an anti-CD40 antibody currently being studied in patients with CLL that has relapsed or is refractory to therapy with fludarabine.
  • Cirmtuzumab. This is a humanized monoclonal antibody that binds to ROR1, a protein found on the surface of CLL cells.
• Combinations of Antibodies With Other Targeted Drugs (Being Investigated in Clinical Trials)
  • ​Combinations with BTK and phosphatidylinositol kinase (PIK) inhibitors. The combination of ibrutinib and rituximab is being studied in the treatment of patients who have high-risk CLL with del(17p).
  • Combinations with immunomodulatory drugs. A study of lenalidomide, rituximab and ibrutinib is researching the effectiveness of this combination for patients with relapsed and refractory CLL.
  • Combinations with BCL2 inhibitors. Venetoclax (Venclexta™) is a BCL2 inhibitor approved for treatment of CLL patients with 17p deletion. It is being studied, in combination with rituximab, for treating patients with relapsed or refractory CLL and for older, untreated patients with CLL and SLL.
• Immunotoxin. An immunotoxin known as “BL22” has shown promising results in treating hairy cell leukemia. A newer version of this drug HA22 (CAT-8015) is now being studied as therapy for relapsed or refractory CLL.
• Immunomodulatory Drug. 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 to determine if it can be used as a maintenance therapy and whether it is safe and effective in further improving the quality and duration of the response to treatment. Clinical trials are also researching the use of lenalidomide in various combinations with other agents, such as rituximab, for first-line CLL treatment and in combination with the BTK inhibitor ibrutinib for patients with advanced relapsed or refractory CLL.
• CAR T-Cell Therapy. This is a type of immunotherapy that consists of engineering patients’ own immune cells first to recognize and then to attack cancerous tumors. This approach has shown very promising results in patients with blood cancers. The T cells are genetically engineered to produce receptors on their surface called “chimeric antigen receptors (CARs).” These receptors recognize and bind to a specific target found on the cancerous cells. Current clinical trials are studying the use of CAR T-cell therapy, directed to CD19, in the treatment of chemotherapy-resistant or relapsed CLL. The results of recent trials have demonstrated that this new approach can induce long-term, diseasefree remissions in CLL patients. 
  For more information on this type of therapy, please see the free LLS booklet Chimeric Antigen Receptor (CAR) T-Cell Therapy Facts.
• PD-1 Checkpoint Inhibitors. A vital part of the immune system is its ability to distinguish healthy cells in the body from those that it recognizes as foreign or harmful. The immune system depends on multiple checkpoints—molecules on certain immune cells that need to be activated (or turned off) in order to start an immune response. Cancer cells sometimes take advantage of these checkpoints to escape the detection of active immune cells. Programmed cell death 1 (PD-1) is a checkpoint protein that is found on the surface of T cells. It normally acts as a type of “off switch” that helps keep immune cells from attacking healthy cells in the body. It accomplishes this when it attaches to a PD-L1—a protein found on some normal cells and also in some cancer cells. When PD-1 binds to PD-L1, a message is sent to the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1 receptors, which help them avoid an immune attack. Checkpoint inhibitors are drugs created to target the PD-1 or PD-L1, blocking their actions, and allowing the immune system to recognize and eliminate cancer cells. Nivolumab (Opdivo®) is one example of this type of drug. This medication has shown great results in other cancers, such as melanoma. Now it is being studied, in combination with the drug ibrutinib, for the treatment of patients who have relapsed or refractory CLL and for patients who have high-risk CLL but have not received any prior treatment. 

Related Links

• Clinical Trial Service: LLS provides personalized clinical trial navigation when appropriate. For more information or to contact us, click here.