What is the mechanism of action of this treatment?

The most common treatments for Chronic Lymphocytic Leukemia (CLL) include BTK inhibitors like acalabrutinib and ibrutinib, which block the BTK enzyme crucial for B-cell receptor signaling, thereby inhibiting the growth and survival of CLL cells. Venetoclax targets BCL2, a protein that prevents cancer cell death, promoting apoptosis in CLL cells. Chemoimmunotherapy, such as bendamustine plus rituximab, combines chemotherapy with monoclonal antibodies to target and kill CLL cells. These treatments are vital as they offer different mechanisms to control disease progression, improve survival rates, and manage symptoms, providing tailored options based on patient-specific factors and disease characteristics.

What side effects are associated with this type of intervention?

Common treatments for Chronic Lymphocytic Leukemia (CLL) include BTK inhibitors like Acalabrutinib and Ibrutinib, as well as other agents like Idelalisib and Bendamustine. BTK inhibitors are associated with side effects such as bleeding, atrial fibrillation, hypertension, and infections. Idelalisib can cause hepatotoxicity, severe diarrhea, colitis, and pneumonitis. Bendamustine, often combined with Rituximab, may lead to hematologic toxicities like neutropenia, thrombocytopenia, and anemia, as well as non-hematologic effects such as nausea, vomiting, and fatigue. These side effects vary in severity and frequency, and patients should discuss them with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several BTK inhibitors for the treatment of Chronic Lymphocytic Leukemia (CLL). Ibrutinib was the first BTK inhibitor approved for CLL and has shown significant efficacy in improving progression-free survival. Following ibrutinib, acalabrutinib was approved as a second-generation BTK inhibitor, offering a similar mechanism of action with potentially fewer side effects. Additionally, venetoclax, a BCL-2 inhibitor, has been approved for CLL and is often used in combination with monoclonal antibodies like obinutuzumab. These approvals have provided multiple targeted therapy options for patients with CLL, particularly those who have relapsed or are refractory to initial treatments.

What other types of research exist?

Promising alternatives to Acalabrutinib for CLL treatment include Ibrutinib, Venetoclax plus Obinutuzumab, and Zanubrutinib. Ibrutinib has demonstrated high overall response rates and is particularly effective in patients with unmutated IGHV. Venetoclax plus Obinutuzumab has shown superior progression-free survival and is suitable for patients with comorbidities. Zanubrutinib is another BTK inhibitor with favorable efficacy and safety profiles in relapsed or refractory CLL.

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Bruton's Tyrosine Kinase (BTK) Inhibitor

Acalabrutinib vs Standard Therapy for Chronic Lymphocytic Leukemia

Phase 3

Waitlist Available

Research Sponsored by Acerta Pharma BV

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment

Must have received ≥ 1 prior systemic therapies for CLL

Must not have

Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome

Prior radio- or toxin-conjugated antibody therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up irc assessments from randomization date until disease progression or death or irc discontinuation on 15jan2019 (as ia per this data cutoff showed crossing superiority boundary) whichever came first, up to 22 months of follow-up

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial compares acalabrutinib with rituximab combined with either idelalisib or bendamustine in patients with chronic lymphocytic leukemia who have already been treated before. Acalabrutinib stops cancer cells from growing, while rituximab helps the immune system kill them. Idelalisib blocks growth signals, and bendamustine damages cancer cell DNA. Acalabrutinib has been approved for the treatment of mantle cell lymphoma and chronic lymphocytic leukemia in the US.

Who is the study for?

This trial is for adults with chronic lymphocytic leukemia (CLL) who have had at least one prior treatment. Participants must have a certain level of physical fitness (ECOG 0-2), not be pregnant or breastfeeding, agree to use effective contraception, and meet specific blood disease criteria without severe other health issues like heart disease or uncontrolled infections.

What is being tested?

The study compares the effectiveness of acalabrutinib against two combinations: rituximab with idelalisib or bendamustine in people with previously treated CLL. It aims to determine which treatment works better for managing this type of leukemia.

What are the potential side effects?

Potential side effects include nausea, diarrhea, fatigue, muscle and bone pain from acalabrutinib; infusion reactions from rituximab; liver problems from idelalisib; and low blood counts leading to infection risk from bendamustine.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My condition requires treatment according to specific leukemia criteria.

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I have had at least one treatment for chronic lymphocytic leukemia.

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I agree not to donate sperm during the trial.

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I have been diagnosed with CLL according to specific criteria.

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I can take care of myself and am up and about more than half of the day.

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I am a man who can father children and agree to use effective birth control.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have or am suspected to have Richter's syndrome or prolymphocytic leukemia.

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I have not had previous treatments with radio- or toxin-conjugated antibodies.

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I am on blood thinners like warfarin.

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I have HIV or another serious infection that is not under control.

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I have liver damage due to medication, alcohol, or fatty liver disease.

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I have been diagnosed with progressive multifocal leukoencephalopathy.

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I have been treated with a BCL-2 or BCR inhibitor before.

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I have had or currently have lung inflammation caused by a drug.

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I need medication that strongly affects liver enzymes.

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I have not had major surgery within the last 30 days.

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I have a condition that affects how my body absorbs nutrients.

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I have a history of unusual bleeding.

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I have been diagnosed with CNS lymphoma or leukemia.

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I have a serious heart condition.

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I had a stem cell transplant less than 6 months ago.

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I need medication for stomach acid.

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I do not have uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ irc assessments from randomization date until disease progression or death or irc discontinuation on 15jan2019 (as ia per this data cutoff showed crossing superiority boundary) whichever came first, up to 22 months of follow-up

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~irc assessments from randomization date until disease progression or death or irc discontinuation on 15jan2019 (as ia per this data cutoff showed crossing superiority boundary) whichever came first, up to 22 months of follow-up

This trial's timeline: 3 weeks for screening, Varies for treatment, and irc assessments from randomization date until disease progression or death or irc discontinuation on 15jan2019 (as ia per this data cutoff showed crossing superiority boundary) whichever came first, up to 22 months of follow-up for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression-free Survival (PFS) Per Independent Review Committee (IRC) Assessment

Secondary study objectives

Duration of Response (DOR) Per Independent Review Committee (IRC) Assessment Based on 15 January 2019 Data Cutoff From Interim Analysis.

Duration of Response (DOR) Per Investigator Assessment Based on 03 September 2021 Data Cutoff

IRC-assessed Overall Response Rate (ORR) Per IWCLL 2008 Criteria Based on Data Cutoff 15 January 2019 From Interim Analysis

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Acalabrutinib (ACP-196)Experimental Treatment1 Intervention

Acalabrutinib (ACP-196) Monotherapy

Group II: Rituximab Plus Idelalisib or BendamustineActive Control3 Interventions

Investigator's Choice of Rituximab Plus Idelalisib or Bendamustine

0 / 23Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Chronic Lymphocytic Leukemia (CLL) include BTK inhibitors like acalabrutinib and ibrutinib, which block the BTK enzyme crucial for B-cell receptor signaling, thereby inhibiting the growth and survival of CLL cells. Venetoclax targets BCL2, a protein that prevents cancer cell death, promoting apoptosis in CLL cells. Chemoimmunotherapy, such as bendamustine plus rituximab, combines chemotherapy with monoclonal antibodies to target and kill CLL cells. These treatments are vital as they offer different mechanisms to control disease progression, improve survival rates, and manage symptoms, providing tailored options based on patient-specific factors and disease characteristics.