CLL - Episode 5

Results From the Phase 2 CAPTIVATE Study

April 23, 2021

FOR YOUR REFERENCE: What Are Clinical Trials?

Clinical trials determine whether a drug works in humans and whether it is safe and effective. To find out whether a drug can be approved for use, the Food and Drug Administration (FDA) requires four phases of a clinical trial. The number of participants increases in each phase, starting from 20 to 80 people for a phase 1 trial to up to 3,000 for a phase 3 trial (Figure 1).1

  • Phase 1: tests an experimental treatment on a small group of often healthy people to judge its safety and side effects and find the correct dosage.
  • Phase 2: focuses on effectiveness and obtains preliminary data on whether the drug works in people who have a certain disease or condition.
  • Phase 3: gathers more information about safety and effectiveness, studies different populations and dosages, and examines use of the drug in combination with other drugs.
  • Phase 4: occurs after FDA approval; monitors safety and effectiveness in large, diverse populations; and collects information on long-term side effects.

FOR YOUR REFERENCE: What Is Chronic Lymphocytic Leukemia?

Chronic lymphocytic leukemia (CLL) is a form of cancer that starts in the blood-forming cells in bone marrow that become certain white blood cells, called lymphocytes. In CLL, cancer occurs in B cells, a type of lymphocyte, which defends your body against infection. These cells change and become cancer cells, or leukemia cells, that can grow out of control and spread by traveling into the blood to other parts of the body.2

Patients with CLL may experience symptoms such as weakness, fatigue, weight loss, chills, fever, night sweats, swollen lymph nodes, pain and a sense of fullness in the belly. Although these signs and symptoms can point to CLL, tests are needed for a diagnosis. Many people with CLL do not have any symptoms at the time of their diagnosis; their leukemia is found during blood tests for unrelated health issues or routine checkups.3 CLL is usually recognized when blood counts performed for unrelated reasons reveal lymphocytosis, or a higher-than-normal amount of lymphocytes in the body.

Treatment options for patients with CLL include the following4:

  1. Watchful waiting.
  2. Radiation therapy.
  3. Chemotherapy.
  4. Immunotherapy.
  5. Targeted therapy.
  6. Clinical trials.

FOR YOUR REFERENCE: What Agents Were Investigated in the CAPTIVATE CLL Study?

Imbruvica (ibrutinib) and Venclexta (venetoclax) are FDA-approved drugs for treating CLL.5,6 In previous trials, these combination of these drugs showed anti-tumor activity and good responses.

Imbruvica (ibrutinib) is an FDA-approved targeted treatment for adult patients with CLL or small lymphocytic lymphoma (SLL) and patients with CLL or SLL with specific mutations. It blocks the activity of Bruton tyrosine kinase (also known as tyrosine-protein kinase or BTK), a protein in B cells that sends “signals” that help B cells stay alive and multiply. Imbruvica blocks BTK signaling to help stop B cells from surviving and multiplying. Imbruvica may slow the spread of CLL or SLL. It is used in initial treatments of CLL and in patients with previous treatment.5 Venclexta is a BCL-2 inhibitor. BCL-2 proteins help CLL cells survive.6,7

Phase 2 CAPTIVATE Study

The CAPTIVATE trial is a phase 2 clinical trial evaluating the effectiveness of the combination of Venclexta and Imbruvica in patients with CLL in the frontline setting, meaning the first treatment in those who have not received prior treatment for their CLL. Patients who were younger than 70 with previously untreated CLL/SLL received an initial three cycles of Imbruvica followed by 12 cycles of Imbruvica in combination with Venclexta.8

Following the initial treatment, 86 patients achieved confirmed undetectable minimal residual disease (MRD), defined as those patients who had a small number of leukemia cells remaining in their body after initial treatment, serially over at least three cycles in both peripheral blood and blood marrow. Of those, 43 patients were randomly assigned to receive placebo and 43 received Imbruvica.8

The 63 patients who did not achieve confirmed undetected MRD continued treatment with either Imbruvica (31 patients) or Imbruvica in combination with Venclexta (32 patients).8

Results

In the confirmed undetectable MRD group, there were similar rates of one-year disease-free survival among patients who received the placebo and those who continued with Imbruvica treatment (95.3% vs. 100%) after the initial 12 cycles of Imbruvica in combination with Venclexta.8

For participants who did not achieve confirmed undetectable MRD, continued treatment with Imbruvica alone or in combination with Venclexta improved their rates of progression-free survival (PFS).8

The PFS study outcomes are represented below as the percentage of patients who did not have cancer spread over the 30-month study period:8

  • Patients with confirmed undetectable MRD who received placebo: 95.3%.
  • Patients with confirmed undetectable MRD who were treated with Imbruvica: 100%.
  • Patients without confirmed undetectable MRD who were treated with Imbruvica: 95.2%.
  • Patients without confirmed undetectable MRD who were treated with Imbruvica in combination with Venclexta: 96.7%.

The safety profile of Imbruvica in combination with Venclexta was consistent with known side effects for each drug. Most side effects were mild in severity and occurred when patients were being treated with early cycles of Imbruvica in combination with Venclexta. Serious side effects occurred in less than 5% of patients: neutropenia (36%), hypertension (10%), thrombocytopenia (5%) and diarrhea (5%).8

First-line treatment with Imbruvica in combination with Venclexta chemotherapy-free treatment option for patients with CLL can show high rates of undetectable MRD.8

Not all patients qualify for certain clinical trials. If you are interested in enrolling in a trial, talk to your doctor about which treatment options would be most appropriate for you.

FOR YOUR REFERENCE: Glossary of Terms

B cells: one type of white blood cell that is an important part of your immune system (the body’s defense against infection)

BCL-2: proteins that help CLL cells survive

Bone marrow: spongy tissue inside of bones; cells that make blood cells are found in the bone marrow

Bruton tyrosine kinase (BTK): a protein in B cells that sends signals that help B cells survive and multiply

Chemotherapy: treatment that uses drugs to stop the growth of cancer cells either by killing the cells or by stopping them from dividing. These drugs are taken by mouth or injected and enter the bloodstream so they can help cancers that spread throughout the body (like CLL). This can affect cancer cells and normal cells

Chronic lymphocytic leukemia: a type of cancer that starts from white blood cells (called lymphocytes) in the bone marrow

Clinical trials: research investigations in which people volunteer to test experimental treatments; these trials evaluate the safety and efficacy of experimental treatments

Efficacy: the ability to produce a desired outcome; in the case of cancer treatments, the desired outcome is a decrease in the number of cancer cells or the disappearance of cancer cells

Hypertension: a blood pressure reading of 140/90 mm Hg or higher; also called high blood pressure

Imbruvica (ibrutinib): an FDA-approved drug indicated for the treatment of adult patients with CLL or SLL with or without 17p deletion. Imbruvica may slow the spread of CLL or SLL

Immunotherapy: type of therapy that uses substances to stimulate or suppress the immune system to help the body fight cancer, infection and other diseases. Some types of immunotherapy only target certain cells of the immune system. Others affect the immune system in a general way

Leukemia: cancer that starts in blood-forming tissue, such as bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the bloodstream

Lymphocytes: a type of white blood cell that is made in the bone marrow and is found in the blood and lymph tissue

Minimal residual disease (MRD): A small number of cancer cells that remain in a patient's body during or after treatment

Neutropenia: a condition in which there is a lower-than-normal number of neutrophils (a type of white blood cell) in the blood

Phase 1: tests an experimental treatment on a small group of often healthy people

Phase 2: uses more people and emphasizes effectiveness

Phase 3: gathers more information about safety and effectiveness, studying different populations and different dosages, using the drug in combination with other drugs

Phase 4: usually occurs after FDA approval of the treatment; monitors safety and effectiveness in large, diverse populations; and collects information on long-term side effects

Primary end point: the main result that is measured at the end of a study to see if a given treatment worked

Progression-free survival (PFS): the length of time during and after the treatment of a disease that a patient lives with the disease, but it does not get worse

Radiation therapy: type of cancer treatment that uses beams of intense energy to kill cancer cells

Side effects: any undesirable experience associated with the use of a medical product in a patient

Small lymphocytic lymphoma (SLL): a cancer that affects a type of white blood cell

Targeted therapy: a cancer treatment that uses drugs to target specific aspects of the cancer cells

Thrombocytopenia: a condition marked by a low number of platelet cell levels in the blood. Platelets help the blood to clot and stop bleeding

Venclexta (venetoclax): A BCL-2 inhibitor indicated for the treatment of adult patients with CCL or SLL

Watchful waiting: a strategy in which treatment is not started right away; instead, symptoms are observed and time is allowed to pass before medical intervention or therapy is used

White blood cells: a type of cell that is found in the blood and lymph tissue that helps fight infections and other diseases. Lymphocytes (T and B cells) are a type of white blood cell.

References

1. What are clinical trials and studies? National Institute on Aging. Accessed March 15, 2021. https://www.nia.nih.gov/health/what-are-clinical-trials-and-studies

2. What is chronic lymphocytic leukemia? American Cancer Society. Updated May 10, 2018. Accessed March 15, 2021. https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/about/what-is-cll.html

3. Signs and symptoms of chronic lymphocytic leukemia. American Cancer Society. Updated May 10, 2018. Accessed March 15, 2021. https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/detection-diagnosis-staging/signs-symptoms.html

4. Chronic lymphocytic leukemia treatment (PDQ)-patient version. National Cancer Institute. Updated November 25, 2020. Accessed March 15, 2021. https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq

5. Imbruvica. Prescribing information. Janssen Biotech, Inc; 2020. Accessed March 22, 2021. https://imbruvica.com/files/prescribing-information.pdf

6. Venclexta. Prescribing information. AbbVie Inc; 2020. Accessed March 17, 2021. https://www.rxabbvie.com/pdf/venclexta.pdf

7. Targeted therapy drugs for chronic lymphocytic leukemia. American Cancer Society. Accessed March 18, 2021. https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/treating/targeted-therapy.html

8. Wierda WG, Tam CS, Allan JN, et al. Imbruvica (Ibr) plus Venclexta (Ven) for first-line treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): 1-year disease-free survival (DFS) results from the MRD cohort of the phase 2 CAPTIVATE study. Abstract presented at 62nd ASH Annual Meeting and Exposition; December 5-8, 2020. Accessed https://ash.confex.com/ash/2020/webprogram/Paper134446.html