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BTK Inhibitor

Acalabrutinib + Venetoclax ± Obinutuzumab for Chronic Lymphocytic Leukemia

Phase 2

Recruiting

Led By William G Wierda

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

Cohort 2: Relapsed after and/or refractory to at least one prior therapy

Eastern Cooperative Oncology Group (ECOG) performance status =< 2

Must not have

Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy with > 20 mg daily of prednisone dose or equivalent

Prior treatment with combined BTKi and BCL2i

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from the start of combination therapy up to end of cycle 4; each cycles 28 days

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new combination therapy for leukemia/lymphoma that has returned or is resistant to treatment. The new therapy includes a targeted drug and an immunotherapy drug.

Who is the study for?

This trial is for adults with high risk, recurrent, or treatment-resistant chronic lymphocytic leukemia or small lymphocytic lymphoma. Participants must have proper liver function, no recent malignancies (with some exceptions), and adequate kidney function. Women of childbearing age must test negative for pregnancy and agree to use contraception; men must also use contraception. Exclusions include active hepatitis C, uncontrolled autoimmune diseases, significant heart issues, certain dietary restrictions like grapefruit consumption, known bleeding disorders, uncontrolled infections, HIV positivity due to drug interactions risks.

What is being tested?

The study tests the effectiveness of acalabrutinib and venetoclax in combination with or without early obinutuzumab in treating CLL/SLL. Acalabrutinib blocks enzymes needed by cancer cells to grow; venetoclax targets proteins essential for their growth; obinutuzumab is an immunotherapy that may help the immune system attack cancer cells.

What are the potential side effects?

Potential side effects include reactions at the infusion site from obinutuzumab; diarrhea and nausea from venetoclax; headaches and bruising from acalabrutinib. There's a risk of infection due to immune system impact by these drugs.

Eligibility Criteria

Inclusion Criteria

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

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My condition did not improve after at least one treatment.

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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 willing to change my acid reflux medication before starting treatment.

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My platelet count is above 30,000 and I haven't had a transfusion in the last 2 weeks.

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I have been diagnosed with CLL/SLL and need treatment according to 2018 guidelines.

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My kidney function, measured by creatinine clearance, is good.

Exclusion Criteria

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

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I have an autoimmune condition needing high-dose steroids.

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I have been treated with both BTK and BCL2 inhibitors.

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I do not have serious heart problems like recent heart attacks or uncontrolled heart rhythm issues.

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I am currently taking warfarin.

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I have not had a stroke or brain bleed in the last 6 months.

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I am HIV positive and on medication.

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I cannot take medications by mouth due to a digestive condition.

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I have active hepatitis C confirmed by a PCR test.

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I do not have any ongoing serious infections.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from the start of combination therapy up to end of cycle 4; each cycles 28 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from the start of combination therapy up to end of cycle 4; each cycles 28 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and from the start of combination therapy up to end of cycle 4; each cycles 28 days for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Incidence of adverse events

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm II (acalabrutinib, venetoclax, early obinutuzumab)Experimental Treatment3 Interventions

Patients receive acalabrutinib PO BID on days 1-28 beginning cycle 2 and venetoclax PO BID on days 1-28 beginning cycle 3. Patients also receive obinutuzumab IV over 4-6 hours on days 1, 2, 8, and 15 of cycle 1 and day 1 of cycles 2-6. Patients who are BM MRD4-positive or in PR receive obinutuzumab IV over 4-6 hours on day 1 cycles 15-20. Treatment repeats every 28 days (or 42 days for cycle 14) for up to 26 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (acalabrutinib, venetoclax, obinutuzumab)Active Control3 Interventions

Patients receive acalabrutinib PO BID on days 1-28. Beginning cycle 3, patients receive venetoclax PO BID on days 1-28. Patients who are BM MRD4-positive or in PR also receive obinutuzumab IV over 4-6 hours on days 1, 2, 8, and 15 of cycle 15 and day 1 of cycles 16-20. Treatment repeats every 28 days (or 42 days for cycle 14) for up to 26 cycles in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Acalabrutinib

2020

Completed Phase 2

~2080

Obinutuzumab

2014

Completed Phase 3

~3470