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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

Must not have

Participants with active cardiovascular disease, corrected QT interval ≥480 ms

Participants with HIV, active infection with HCV or HBV, or any uncontrolled active systemic infection

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

No Placebo-Only Group

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.

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.

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.

Exclusion Criteria

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

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I have heart disease or a long QT interval.

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I do not have HIV, hepatitis B or C, or any uncontrolled infections.

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I do not have any severe illnesses or organ problems.

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I am not pregnant or breastfeeding.

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

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I have uncontrolled autoimmune blood disorders.

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I am currently on IV antibiotics or antivirals for an infection.

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I have a history of bleeding disorders.

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I am on blood thinners like warfarin.

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I need to take medication to reduce stomach acid.

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I am still experiencing moderate to severe side effects from previous cancer treatments.

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

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

Primary study objectives

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 study objectives

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

Musculoskeletal chest pain

Dizziness

Nausea

Oedema peripheral

Thrombocytosis

Full Blood Count decreased

Leukopenia

Hyponatraemia

Haematuria

Intervertebral disc degeneration

Contusion

Hypochloraemia

Vomiting

Diarrhea

100%

80%

60%

40%

20%

Study treatment Arm

ACP-196 + Methotrexate

Placebo + Methotrexate

Awards & Highlights

No Placebo-Only Group

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

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

acalabrutinib

2018

Completed Phase 2

~80

Rituximab

1999

Completed Phase 4

~2990