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Bruton's Tyrosine Kinase (BTK) Inhibitor

Acalabrutinib + Anti-CD20 + Venetoclax for Chronic Lymphocytic Leukemia

Phase 1

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

Participants with a diagnosis of intermediate or high risk CLL (or variant immunophenotype), SLL, or B-cell prolymphocytic leukemia (B-PLL) by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Hallek et al. 2008)

Participants must satisfy one of the following criteria for active disease requiring therapy: evidence of marrow failure, massive splenomegaly, massive nodes or lymphadenopathy, constitutional symptoms

Timeline

Screening 3 weeks

Treatment Varies

Follow Up cohort 1: pre-dose; 0.5, 1, 2, 3, 4, 6, and 24 hours post-dose for cycle 1. cohorts 3 and 4: pre-dose; 0.5, 1, 2, 3, 4, 6, and 24 hours post-dose for cycles 1, 3, and 5.(each cycle is 28 days)

Awards & highlights

Study Summary

This trial is testing a new cancer drug, acalabrutinib, to see if it is safe and effective when used with another drug, obinutuzumab.

Who is the study for?

This trial is for adults with certain types of leukemia and lymphoma, including CLL/SLL/PLL. Participants can be treatment-experienced or untreated, depending on the cohort they qualify for. They must have adequate organ function, not be pregnant or breastfeeding, agree to contraception if applicable, and cannot have secondary cancers affecting life expectancy or confounding factors.Check my eligibility

What is being tested?

The safety and efficacy of acalabrutinib combined with obinutuzumab are being tested in four cohorts of participants with different disease statuses (treated/untreated). The study will assess how well this combination works for those who meet specific health criteria.See study design

What are the potential side effects?

Potential side effects may include digestive issues due to acalabrutinib's effect on GI function; blood disorders from bone marrow involvement; fatigue; risk of infection; and possible complications related to liver function as indicated by required organ function tests.

Eligibility Criteria

Inclusion Criteria

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

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I have been diagnosed with a certain type of leukemia that is considered intermediate or high risk.

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I need treatment because of symptoms like anemia, large spleen or lymph nodes, or fever and weight loss.

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My organs work well, I don't have another cancer, and my doctor thinks I'll live more than 2 years.

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I am 18 years old or older.

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I can swallow pills without any issues.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ cohort 1: pre-dose; 0.5, 1, 2, 3, 4, 6, and 24 hours post-dose for cycle 1. cohorts 3 and 4: pre-dose; 0.5, 1, 2, 3, 4, 6, and 24 hours post-dose for cycles 1, 3, and 5.(each cycle is 28 days)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~cohort 1: pre-dose; 0.5, 1, 2, 3, 4, 6, and 24 hours post-dose for cycle 1. cohorts 3 and 4: pre-dose; 0.5, 1, 2, 3, 4, 6, and 24 hours post-dose for cycles 1, 3, and 5.(each cycle is 28 days)

This trial's timeline: 3 weeks for screening, Varies for treatment, and cohort 1: pre-dose; 0.5, 1, 2, 3, 4, 6, and 24 hours post-dose for cycle 1. cohorts 3 and 4: pre-dose; 0.5, 1, 2, 3, 4, 6, and 24 hours post-dose for cycles 1, 3, and 5.(each cycle is 28 days) for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Number of Participants With Abnormal Vital Signs Reported as TEAEs in all Cohorts

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in all Cohorts

Number of Participants With Treatment-Emergent Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 Abnormalities in Laboratory Parameters in all Cohorts

+2 more

Secondary outcome measures

Apparent Volume of Distribution (Vz/F) of Acalabrutinib in Cohorts 1, 3, and 4

Apparent oral clearance (CL/F) of Administration of Acalabrutinib in Cohorts 1, 3, and 4

Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to infinity (AUC0-inf) of Acalabrutinib and its Metabolite ACP-5862 in Cohorts 1, 3, and 4

+20 more

Side effects data

From 2016 Phase 2 trial • 31 Patients • NCT02387762

13%

Anaemia

Nausea

Leukopenia

Intervertebral disc degeneration

Dizziness

Oedema peripheral

Diarrhea

Vomiting

Full Blood Count decreased

Contusion

Thrombocytosis

Hyponatraemia

Hypochloraemia

Musculoskeletal chest pain

Haematuria

100%

80%

60%

40%

20%

Study treatment Arm

Placebo + Methotrexate

ACP-196 + Methotrexate

Trial Design

4Treatment groups

Experimental Treatment

Group I: Cohort 4: Acalabrutinib+Obinutuzumab+Venetoclax (Treatment-naive)Experimental Treatment3 Interventions

The treatment-naïve participants with CLL will receive oral acalabrutinib, IV infusion of obinutuzumab, and oral venetoclax. Participants will receive acalabrutinib Dose 2 BID in 28-day continuous cycles until disease progression, an unacceptable drug-related toxicity, or per the investigator the study treatment is intolerable or no longer in participant's best interest, whichever occurs first. Participants will receive obinutuzumab for total 6 cycles (from Cycles 2 to 7) as Dose 1 on Cycle 2 Day 1, Dose 2 on Cycle 2 Day 2, Dose 3 on Cycle 2 Days 8 and 15, and Dose 3 on Day 1 of Cycles 3 to 7. Participants will receive venetoclax weekly ramp-up schedule over 5 weeks from Cycles 3 to 15 as Dose 1 QD for 1 week on Cycle 3 Day 1, Dose 2 QD for 1 week on Cycle 3 Day 8, Dose 3 QD for 1 week on Cycle 3 Day 15, Dose 4 QD for 1 week on Cycle 3 Day 22, and from Cycle 4 Day 1 participants will receive Dose 5 QD until completion of Cycle 15.

Group II: Cohort 3: Acalabrutinib+Rituximab+Venetoclax (R/R)Experimental Treatment3 Interventions

The R/R participants with CLL will receive oral acalabrutinib, IV infusion of rituximab, and oral venetoclax. Participants will receive acalabrutinib Dose 2 BID in 28-day continuous cycles until disease progression, an unacceptable drug-related toxicity, or per the investigator the study treatment is intolerable or no longer in participant's best interest, whichever occurs first. Participants will receive rituximab for total 6 cycles (from Cycles 2 to 7) as Dose 1 on Cycle 2 Day 1, followed by Dose 1 every 3 weeks (Q3W) for 3 doses, then every 4 weeks (Q4W) for 5 doses (total 9 infusions through the end of Cycle 7). Participants will receive venetoclax weekly ramp-up schedule over 5 weeks from Cycles 3 to 15, Dose 1 QD for 1 week on Cycle 3 Day 1, Dose 2 QD for 1 week on Cycle 3 Day 8, Dose 3 QD for 1 week on Cycle 3 Day 15, Dose 4 QD for 1 week on Cycle 3 Day 22, and Dose 5 QD from Cycle 4 Day 1 until completion of Cycle 15.

Group III: Cohort 2: Acalabrutinib+Obinutuzumab (Treatment-naive)Experimental Treatment2 Interventions

Dose-escalation and dose-expansion phases will be conducted for treatment-naïve participants with CLL/ small lymphocytic lymphoma (SLL). In dose-escalation phase, participants will receive oral acalabrutinib Dose 2 BID in first cycle (28-day cycle). In dose- expansion phase, participants will receive oral acalabrutinib Dose 2 BID in 28-day continuous cycles; and will receive IV infusion of obinutuzumab for total 6 cycles (from Cycles 2 to 7) as on Cycle 2 Day 1 participants will receive Dose 1, on Cycle 2 Day 2 participants will receive Dose 2, on Cycle 2 Days 8 and 15 participants will receive Dose 3, and on Day 1 of Cycles 3 to 7 participants will receive Dose 3. Participants will continue to receive acalabrutinib Dose 2 BID until disease progression, an unacceptable drug-related toxicity, or per the investigator the study treatment is intolerable or no longer in participant's best interest, whichever occurs first.

Group IV: Cohort 1: Acalabrutinib+Obinutuzumab (R/R)Experimental Treatment2 Interventions

Dose-escalation and dose-expansion phases will be conducted for relapsed/refractory (R/R) participants with CLL. In dose-escalation phase, participants will receive oral acalabrutinib Dose 1 once daily (QD), later the dose was switched to Dose 2 twice daily (BID) per Amendment 02. In dose- expansion phase, participants will receive oral acalabrutinib Dose 2 BID in 28-day continuous cycles; and will receive intravenous (IV) infusion of obinutuzumab for total 6 cycles (from Cycles 2 to 7) as on Cycle 2 Day 1 participants will receive Dose 1, on Cycle 2 Day 2 participants will receive Dose 2, on Cycle 2 Days 8 and 15 participants will receive Dose 3, and on Day 1 of Cycles 3 to 7 participants will receive Dose 3. Participants will continue to receive acalabrutinib Dose 2 BID until disease progression, an unacceptable drug-related toxicity, or per the investigator the study treatment is intolerable or no longer in participant's best interest, whichever occurs first.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Rituximab

1999

Completed Phase 4

~1880

acalabrutinib

2018

Completed Phase 2

~80

Obinutuzumab

2015

Completed Phase 3

~3250

Venetoclax

2019

Completed Phase 3

~1990

0 / 5Eligibility criteria met

Find a Location

Who is running the clinical trial?

Acerta Pharma BVLead Sponsor

45 Previous Clinical Trials

5,856 Total Patients Enrolled

AstraZeneca Study Information CenterStudy Director1-877-240-9479; information.center@astrazeneca.com

Media Library

Acalabrutinib (Bruton's Tyrosine Kinase (BTK) Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT02296918 — Phase 1

Chronic Lymphocytic Leukemia Research Study Groups: Cohort 2: Acalabrutinib+Obinutuzumab (Treatment-naive), Cohort 1: Acalabrutinib+Obinutuzumab (R/R), Cohort 3: Acalabrutinib+Rituximab+Venetoclax (R/R), Cohort 4: Acalabrutinib+Obinutuzumab+Venetoclax (Treatment-naive)

Chronic Lymphocytic Leukemia Clinical Trial 2023: Acalabrutinib Highlights & Side Effects. Trial Name: NCT02296918 — Phase 1

Acalabrutinib (Bruton's Tyrosine Kinase (BTK) Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT02296918 — Phase 1

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

Does this new treatment have a similar success rate as other therapies?

"Acalabrutinib is being studied in 710 different ongoing clinical trials, with 129 of those studies at the third and final phase. Even though a large portion of these trials are taking place in Edmonton, Alberta, there are over 23000 locations worldwide where research is being conducted."

Answered by AI

Does acalabrutinib have the approval of the FDA?

"Given that this is a Phase 1 trial with limited data to support both safety and efficacy, our team has rated the risk of taking acalabrutinib as a 1."

Answered by AI

What medical condition does acalabrutinib commonly treat?

"Acalabrutinib is most often used as a treatment for diffuse large b-cell lymphoma (dlbcl). However, it can also be effective in treating other conditions like b-cell lymphomas, polyangium, and pemphigus vulgaris."

Answered by AI

What are the researchers hoping to achieve with this experiment?

"The main goal of this trial, which will last for 12 months, is to evaluate the safety of the combination of acalabrutinib and venetoclax. Additionally, the study wants to collect data on how well the treatment works at fighting the cancer (DOR), whether it helps patients live longer (OS), and what percentage of patients respond to the treatment (ORR)."

Answered by AI

Are people with the specific ailment still being allowed to participate in this experiment?

"This particular clinical trial, which was first posted on December 22nd 2014 and last updated on March 11th 2022, is not recruiting patients at this juncture. There are however, 2286 other medical studies that are actively searching for participants."

Answered by AI

Recent research and studies

Cancer DiscoveryJournal

Acalabrutinib Plus Obinutuzumab in Treatment-naïve and Relapsed/refractory Chronic Lymphocytic Leukemia

Woyach, Jennifer A., James S. Blachly, Kerry A. Rogers, Seema A. Bhat, Mojgan Jianfar, Gerard Lozanski, David M. Weiss, et al.. 2020. “Acalabrutinib Plus Obinutuzumab in Treatment-naïve and Relapsed/refractory Chronic Lymphocytic Leukemia”. Cancer Discovery. American Association for Cancer Research (AACR). doi:10.1158/2159-8290.cd-19-1130.

British Journal of Health PsychologyJournal

Illness Representations and Psychological Outcomes in Chronic Lymphocytic Leukaemia

Arrato, Nicole A., Thomas R. Valentine, John C. Byrd, Jeffrey A. Jones, Kami J. Maddocks, Jennifer A. Woyach, and Barbara L. Andersen. 2021. “Illness Representations and Psychological Outcomes in Chronic Lymphocytic Leukaemia”. British Journal of Health Psychology. Wiley. doi:10.1111/bjhp.12562.

clinicaltrials.govStudy

Acalabrutinib in Combination With Anti-CD20 and Venetoclax in Relapsed/Refractory or Untreated CLL/SLL/PLL

2014. "Acalabrutinib in Combination With Anti-CD20 and Venetoclax in Relapsed/Refractory or Untreated CLL/SLL/PLL". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02296918.