Actively Recruiting

Phase 2
Age: 18Years +
All Genders
NCT05388006

Acalabrutinib, Venetoclax and Durvalumab for the Treatment of Richter Transformation From Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Led by Mayo Clinic · Updated on 2026-03-25

27

Participants Needed

3

Research Sites

215 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

This phase II trial tests whether acalabrutinib, venetoclax, and durvalumab work in treating patients with Richter transformation from chronic lymphocytic leukemia or small lymphocytic lymphoma. Richter transformation is a rare condition in which chronic lymphocytic leukemia or small lymphocytic lymphoma changes into a fast-growing type of lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving acalabrutinib, venetoclax, and durvalumab may help improve survival in patients with Richter transformation.

CONDITIONS

Official Title

Acalabrutinib, Venetoclax and Durvalumab for the Treatment of Richter Transformation From Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age 18 years or older and able to provide consent and follow-up
  • Diagnosis of chronic lymphocytic leukemia (CLL) by IWCLL 2018 criteria or small lymphocytic lymphoma (SLL) by WHO 2008 criteria
  • Biopsy-proven Richter's transformation of CLL
  • Patients with prior CLL therapy can enroll if they have not received Richter transformation-specific therapy
  • No other standard therapy options available for Richter transformation per physician
  • Measurable disease detectable by PET or CT (≥ 1 cm in diameter)
  • ECOG performance status of 0, 1, or 2
  • Adequate blood counts and organ function as specified within 14 days prior to registration
  • Negative pregnancy test for women of childbearing potential within 7 days prior to registration
  • Willingness to use highly effective contraception if of childbearing potential during treatment and for 180 days after last dose
  • Able to provide informed written consent
  • Willing to return for follow-up and provide tissue, blood, and bone marrow samples for research
Not Eligible

You will not qualify if you...

  • Uncontrolled serious illnesses such as symptomatic arrhythmias, congestive heart failure, recent myocardial infarction (≤ 3 months), class 3 or 4 heart disease, uncontrolled hypertension, or unstable angina
  • Serious chronic gastrointestinal conditions causing diarrhea
  • History or ongoing progressive multifocal leukoencephalopathy (PML)
  • Stroke or intracranial hemorrhage within 6 months before treatment
  • History of bleeding disorders such as hemophilia or von Willebrand disease
  • Active uncontrolled infections requiring systemic therapy, including tuberculosis and positive CMV PCR unless controlled
  • Known HIV infection
  • Active hepatitis B or C infection unless adequately treated and controlled
  • Pregnant or nursing women
  • Men and women unwilling to use highly effective contraception during and 180 days after treatment
  • Recent use of other investigational agents (except venetoclax, acalabrutinib, or ibrutinib) within 5 half-lives
  • Prior durvalumab treatment
  • Active or recent autoimmune or inflammatory disorders not controlled, with some exceptions
  • Evidence of interstitial lung disease or active non-infectious pneumonitis
  • Psychiatric or substance abuse disorders interfering with study compliance
  • Active central nervous system lymphoma or malignant lymphoma in cerebrospinal fluid needing treatment
  • Significant coagulopathy
  • Allogeneic stem cell transplant within 2 years or history of graft versus host disease
  • Use of strong CYP3A inducers/inhibitors that cannot be changed before treatment
  • Use of proton pump inhibitors unless switched to alternatives
  • History of other primary malignancies with some exceptions
  • Recent or ongoing immunosuppressive medication use with exceptions
  • Radiation therapy within 1 week prior to registration
  • Major surgery within 28 days prior to registration
  • Body weight ≤ 30 kg
  • Life expectancy less than 12 weeks

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 3 locations

1

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States, 94304

Not Yet Recruiting

2

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

Actively Recruiting

3

Washington University School of Medicine

St Louis, Missouri, United States, 63110

Withdrawn

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Research Team

C

Clinical Trials Referral Office

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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