306 Participants Needed

Acalabrutinib for Chronic Lymphocytic Leukemia

Recruiting at 12 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Acerta Pharma BV
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This study is evaluating the safety and efficacy of a new BTK inhibitor, acalabrutinib, for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take proton-pump inhibitors or certain blood thinners like warfarin within 7 days of starting the study drug. If you're on these medications, you may need to discuss alternatives with your doctor.

What data supports the effectiveness of the drug Acalabrutinib for treating Chronic Lymphocytic Leukemia?

Research shows that Acalabrutinib, a drug that targets a specific protein involved in cancer cell growth, significantly extends the time patients live without their disease getting worse compared to standard treatments. It has been approved in the EU and the US for both newly diagnosed and previously treated patients, demonstrating improved safety and effectiveness.12345

Is acalabrutinib safe for humans?

Acalabrutinib, also known as Calquence, has been shown to have a generally favorable safety profile in patients with chronic lymphocytic leukemia, though it may increase the risk of certain side effects like neutropenia (low white blood cell count), leukopenia (low white blood cell count), and cardiac events such as atrial fibrillation (irregular heartbeat). Most common side effects include headache, diarrhea, and infections, but the overall benefit-risk ratio is considered positive.12367

How is the drug Acalabrutinib unique for treating chronic lymphocytic leukemia?

Acalabrutinib is unique because it is a highly selective Bruton tyrosine kinase inhibitor, which means it specifically targets a protein that helps cancer cells grow and survive, leading to longer progression-free survival compared to some standard treatments. It is taken orally and has a favorable safety profile, making it a promising option for both newly diagnosed and relapsed patients.12348

Research Team

AC

Acerta Clinical Trials

Principal Investigator

1-888-292-9613 acertamc@dlss.com

Eligibility Criteria

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.

Inclusion Criteria

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).
I am 18 or older with CLL/SLL and cannot tolerate ibrutinib due to its side effects.
I am 18 or older with CLL/SLL and need treatment but can't or don't want to undergo chemoimmunotherapy.
See 4 more

Exclusion Criteria

I do not have active HIV, hepatitis B, or C, or any uncontrolled infection.
Serum amylase > 1.5 x ULN or serum lipase > 1.5 x ULN.
I do not have uncontrolled AIHA or ITP requiring high doses of steroids.
See 23 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral acalabrutinib in various dosing regimens until disease progression or intolerance

Until disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 years 6 months

Treatment Details

Interventions

  • Acalabrutinib
Trial OverviewThe 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.
Participant Groups
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.

Acalabrutinib is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Calquence for:
  • Mantle cell lymphoma
  • Chronic lymphocytic leukemia
  • Small lymphocytic lymphoma
🇪🇺
Approved in European Union as Calquence for:
  • Chronic lymphocytic leukemia
  • Small lymphocytic lymphoma
  • Mantle cell lymphoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Acerta Pharma BV

Lead Sponsor

Trials
46
Recruited
5,900+

Findings from Research

In a phase III study involving 310 patients with relapsed/refractory chronic lymphocytic leukemia (CLL), acalabrutinib monotherapy significantly improved progression-free survival (PFS) compared to investigator's choice treatments, with a median PFS not reached for acalabrutinib versus 16.5 months for the comparator group.
Acalabrutinib demonstrated a favorable safety profile, with serious adverse events occurring in 29% of patients, compared to 56% for idelalisib plus rituximab and 26% for bendamustine plus rituximab, indicating it may be a safer option for patients.
ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia.Ghia, P., Pluta, A., Wach, M., et al.[2021]
Acalabrutinib has been approved in the EU for treating both treatment-naïve and relapsed/refractory chronic lymphocytic leukemia (CLL), showing significant improvements in progression-free survival compared to standard therapies in two phase III trials involving adult patients.
The safety profile of acalabrutinib is generally acceptable, with common side effects including headache, diarrhea, and infections, and the overall benefit-risk ratio is considered positive for its use in CLL.
EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia.Delgado, J., Josephson, F., Camarero, J., et al.[2021]
Acalabrutinib, a selective Bruton tyrosine kinase inhibitor, showed improved safety outcomes compared to other targeted therapies for treatment-naïve chronic lymphocytic leukemia (CLL) patients, although it was associated with a higher risk of neutropenia and leukopenia in some cases.
The analysis indicated that acalabrutinib (with or without obinutuzumab) had similar efficacy in terms of progression-free survival compared to other treatments, suggesting it is a safe and effective option for CLL patients.
Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia.Davids, MS., Telford, C., Abhyankar, S., et al.[2021]

References

ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. [2021]
EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia. [2021]
Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia. [2021]
Acalabrutinib Versus Investigator's Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results. [2022]
Acalabrutinib and Its Therapeutic Potential in the Treatment of Chronic Lymphocytic Leukemia: A Short Review on Emerging Data. [2020]
Acalabrutinib-Related Cardiac Toxicities in Patients with Chronic Lymphocytic Leukemia: A Meta-Analysis of Randomized Controlled Trials. [2022]
Acalabrutinib in treatment-naive chronic lymphocytic leukemia. [2022]
Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. [2021]