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BTK Inhibitor

Acalabrutinib + Venetoclax + Durvalumab for Richter Syndrome

Phase 2

Recruiting

Led By Paul J. Hampel, MD

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

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

Must have

Diagnosis of CLL according to the IWCLL 2018 criteria or SLL according to the WHO 2008 criteria with specific documentation requirements

Biopsy-proven Richter's transformation of the CLL

Must not have

Recent allogenic stem cell transplant or chronic GVHD

Uncontrolled cardiovascular disease, hypertension, or angina

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from registration to death due to any cause, assessed up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests acalabrutinib, venetoclax, and durvalumab in treating Richter transformation, a rare condition in which chronic lymphocytic leukemia or small lymphocytic lymphoma changes into a fast-growing type of lymphoma.

Who is the study for?

Adults diagnosed with Richter transformation from chronic lymphocytic leukemia or small lymphocytic lymphoma can join this trial. They must have a certain level of physical fitness, no pregnancy, and agree to use effective contraception. People who've had recent heart issues, uncontrolled infections, autoimmune diseases without remission for 3 years (except stable hypothyroidism), active pneumonitis, CNS involvement by cancer requiring therapy, or those on strong CYP3A inhibitors/inducers are excluded.

What is being tested?

The trial is testing the combination of acalabrutinib (blocks enzymes for cell growth), venetoclax (BCL-2 inhibitor stopping cancer cell survival), and durvalumab (monoclonal antibody boosting immune attack on cancer). It aims to see if this combo improves survival in patients with fast-growing types of lymphoma developed from other blood cancers.

What are the potential side effects?

Potential side effects include diarrhea, risk of infection due to immune system suppression by durvalumab, liver function changes from acalabrutinib and venetoclax. There may also be risks related to low blood counts leading to fatigue or bleeding complications.

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 CLL or SLL based on specific criteria.

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My CLL has transformed into a more aggressive form.

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My liver tests for bilirubin, AST, and ALT are within required ranges.

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I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

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

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I recently had a stem cell transplant or have chronic GVHD.

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I do not have uncontrolled heart problems.

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I have had cancer other than my current diagnosis.

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I have lung scarring or inflammation.

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I have a serious blood clotting disorder.

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My cancer has spread to my brain or spinal fluid.

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I regularly take medications that affect CYP3A.

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I have a long-term stomach or bowel condition that causes diarrhea.

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I have been diagnosed with HIV, hepatitis B, or hepatitis C.

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I am not willing to use effective birth control methods.

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I do not have any ongoing serious infections or tuberculosis.

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I am currently taking or have recently taken medication that weakens my immune system.

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I have an active autoimmune or inflammatory condition.

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My body weight is 30 kg or less.

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I have had progressive multifocal leukoencephalopathy in the past.

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I have not had a recent stroke or bleeding disorder.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from registration to death due to any cause, assessed up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from registration to death due to any cause, assessed up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and from registration to death due to any cause, assessed up to 5 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Progression free survival

Secondary study objectives

Incidence of adverse events

Overall response rate

Overall survival

+2 more

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

1Treatment groups

Experimental Treatment

Group I: Treatment (acalabrutinib, durvalumab, venetoclax)Experimental Treatment3 Interventions

Patients receive acalabrutinib PO BID on days 1-28, durvalumab IV over 1 hour on day 1, and venetoclax PO QD on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive acalabrutinib PO BID and venetoclax PO QD on days 1-90. Treatment repeats every 90 days for 4 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

Durvalumab

2017

Completed Phase 2

~3750