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Bruton Tyrosine Kinase Inhibitor

Acalabrutinib for Chronic Lymphocytic Leukemia

Phase 1 & 2

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 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for requiring treatment: Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin < 10 g/dL) and/or thrombocytopenia (platelets < 100,000/μL). Massive (i.e., ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly. Massive nodes (i.e., ≥ 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy. Progressive lymphocytosis with an increase of > 50% over a 2-month period or a lymphocyte doubling time (LDT) of < 6 months. The LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts (ALC) obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In participants with initial blood lymphocyte counts of < 30 X 10^9/L (30,000/μL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy. Constitutional symptoms documented in the participant's chart with supportive objective measures, as appropriate, defined as ≥ 1 of the following disease-related symptoms or signs: i. Unintentional weight loss ≥ 10% within the previous 6 months before screening. ii. Fevers higher than 100.5°F or 38.0°C for 2 or more weeks before screening without evidence of infection. iii. Night sweats for > 1 month before screening without evidence of infection. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. Agreement to use highly effective methods of contraception during the study and for 2 days after the last dose of study drug if sexually active and able to bear or beget children (see Section 3.7.9 for list of highly effective methods of contraception). Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local participant privacy regulations).

Ibrutinib Intolerant only: Men and women ≥ 18 years of age with confirmed diagnosis of CLL/SLL who are not tolerating ibrutinib due to ibrutinib-related AEs.

Must not have

Uncontrolled autoimmune hemolytic anemia (AIHA) or immune thrombocytopenic purpura (ITP) defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (> 20 mg daily of prednisone daily or equivalent).

Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or left ventricular ejection fraction (LVEF) ≤ 40%.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on day 1 and day 8

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug to treat leukemia.

Who is the study for?

This trial is for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who need treatment, have specific symptoms like anemia or large spleen, and haven't responded well to other therapies. It's also for those intolerant to a drug called ibrutinib. People can't join if they've had certain recent treatments, uncontrolled heart issues, active infections like HIV/HBV/HCV, severe bleeding disorders, major surgery within the last month, or are pregnant.

What is being tested?

The trial is testing Acalabrutinib's safety and effectiveness in treating CLL/SLL. Participants will take this new BTK inhibitor to see how it helps manage their leukemia compared to current standard treatments.

What are the potential side effects?

Acalabrutinib may cause side effects such as headaches, diarrhea, muscle pain, reduced blood cell counts leading to increased infection risk or bruising/bleeding tendencies. Some people might experience more serious issues affecting the heart rhythm.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 or older with CLL/SLL and cannot tolerate ibrutinib due to its side effects.

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I have a lymph node larger than 2 cm due to my CLL/SLL.

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I am 18 or older with a biopsy showing I have DLBCL from Richter's transformation or prolymphocytic leukemia.

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I am 18 or older with CLL/SLL that didn't respond to at least 2 treatments.

Exclusion Criteria

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

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I do not have uncontrolled AIHA or ITP requiring high doses of steroids.

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I do not have serious heart problems like recent heart attacks or severe heart failure.

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I do not have significant gastrointestinal issues or surgeries affecting digestion.

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I haven't had immunotherapy in the last 4 weeks.

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I am experiencing side effects from cancer treatment, excluding hair loss.

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I need medication for stomach acid, like omeprazole.

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I have a bleeding disorder such as hemophilia or von Willebrand disease.

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I have not had major surgery in the last 4 weeks.

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My kidneys are not functioning well, with a creatinine clearance of less than 30 mL/min.

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My lymphoma has spread to my brain or spinal cord.

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I have never had Richter's transformation.

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My heart's electrical activity is normal, without specific severe issues.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on day 1 and day 8

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on day 1 and day 8

This trial's timeline: 3 weeks for screening, Varies for treatment, and predose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, and 24 hours postdose on day 1 and day 8 for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Apparent Oral Clearance (CL/F) of Acalabrutinib

Apparent Volume of Distribution (Vz/F) of Acalabrutinib

Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours (AUC0-6) of Acalabrutinib

+11 more

Secondary study objectives

Duration of Response (DOR) as Assessed by the Investigator

Percentage of Participants With Objective Response (OR) as Assessed by the Investigator

Progression Free Survival (PFS) as Assessed by the Investigator

Side effects data

From 2020 Phase 2 trial • 177 Patients • NCT04346199

Headache

Septic shock

Ischaemic stroke

Chronic obstructive pulmonary disease

100%

80%

60%

40%

20%

Study treatment Arm

BSC Alone

Acalabrutinib + BSC

Awards & Highlights

No Placebo-Only Group

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

Trial Design

5Treatment groups

Experimental Treatment

Group I: Treatment-naive CohortExperimental Treatment1 Intervention

Treatment-naïve participants with confirmed CLL or SLL, will receive oral acalabrutinib Dose 5 QD (Cohort 7, later will be switched to Dose 1 BID per protocol amendment 6) or Dose 1 BID (Cohort 11) until disease progression or until the investigator will consider the study treatment to be intolerable or no longer in the participant's best interest.

Group II: Richters Syndrome/Prolymphocytic Leukemia Transformation CohortExperimental Treatment1 Intervention

Participants with diffuse large B-cell lymphoma (DLBCL) Richter's transformation (RS) or prolymphocytic leukemia (PLL) transformation, will receive oral acalabrutinib Dose 5 BID (Cohort 9) until disease progression or until the investigator will consider the study treatment to be intolerable or no longer in the participant's best interest.

Group III: Relapsed/Refractory CohortExperimental Treatment1 Intervention

Phase 1 (dose-escalation) and Phase 2 (dose-expansion) will be conducted for participants with relapsed/refractory CLL or SLL. In Phase 1, participants will receive oral once daily (QD) acalabrutinib at Dose 1 (Cohort 1), Dose 2 (Cohort 2a), Dose 3 (Cohort 3), and Dose 4 (Cohort 4a), and twice daily (BID) acalabrutinib at Dose 1 (Cohort 2b) and Dose 5 (Cohort 4b) for 28 days (1 cycle). In Phase 2, participants will receive oral acalabrutinib at Dose 1 BID (Cohort 2b) or Dose 5 QD (Cohort 2c, later will be switched to Dose 1 BID per protocol amendment 6) until disease progression or until the investigator will consider the study treatment to be intolerable or no longer in the participant's best interest. Participants from Phase 1 will be continued to receive Dose 1 BID until disease progression or until the investigator will consider the study treatment to be intolerable or no longer in the participant's best interest.

Group IV: Ibrutinib-intolerant CohortExperimental Treatment1 Intervention

Participants with confirmed CLL or SLL and were not tolerating ibrutinib treatment, will receive oral acalabrutinib Dose 5 QD (Cohort 8a, later switched to Dose 1 BID per protocol amendment 4) or Dose 1 BID (Cohort 8b) until disease progression or until the investigator will consider the study treatment to be intolerable or no longer in the participant's best interest.

Group V: Ibrutinib Relapsed/Refractory CohortExperimental Treatment1 Intervention

Participants with confirmed CLL/SLL and had relapsed/refractory to ibrutinib treatment, will receive oral acalabrutinib Dose 5 QD (Cohort 10) until disease progression or until the investigator will consider the study treatment to be intolerable or no longer in the participant's best interest.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Acalabrutinib

2020

Completed Phase 2

~2080

0 / 17Eligibility criteria met

Find a Location

Who is running the clinical trial?

Acerta Pharma BVLead Sponsor

45 Previous Clinical Trials

5,619 Total Patients Enrolled

Acerta Clinical TrialsStudy Director1-888-292-9613 acertamc@dlss.com

17 Previous Clinical Trials

2,120 Total Patients Enrolled

Media Library

Acalabrutinib (Bruton Tyrosine Kinase Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT02029443 — Phase 1 & 2

$Chronic Lymphocytic Leukemia Research Study Groups: Richters Syndrome/Prolymphocytic Leukemia Transformation Cohort, Ibrutinib-intolerant Cohort, Ibrutinib Relapsed/Refractory Cohort, Relapsed/Refractory Cohort, Treatment-naive Cohort$