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

Recruiting now · Phase 2

Conditions studied: Chronic Lymphocytic Leukemia, Richter Syndrome, Small Lymphocytic Lymphoma

In brief

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.

Key facts

Study ID

NCT05388006

Run by

Mayo Clinic

People needed

27

Starts

2023-01-05

Expected to finish

2027-02-22

Last updated by the study team

2026-03-25

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age >= 18 years willing to provide consent and follow-up
• Diagnosis of CLL according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria (Hallek et al., 2018) or small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) 2008 criteria (Harris, 1999). This includes previous documentation of:
• Biopsy-proven SLL according to WHO 2008 criteria, or
• Diagnosis of CLL according to IWCLL 2018 criteria as evidenced by all of the following:
• Peripheral blood B cell count of >= 5 x 10\^9/L consisting of small to moderate size lymphocytes (If there are enough evidence to document the prior diagnosis of CLL, it is not required to meet the criteria of peripheral blood B cell count more than 5 x 10\^9/L )
• Immunophenotyping consistent with CLL defined as:
• The predominant population of lymphocytes share both B-cell antigens (CD19, CD20 [typically dim expression], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)
• Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. immunoglobulin heavy chain variable [IGHV] analysis)
• NOTE: Splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL
• Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescence in situ hybridization (FISH) analysis for t(11;14)(IgH/CCND1) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy
• If prior CLL diagnosis was confirmed, or CLL diagnosis was confirmed on bone marrow examination or tissue biopsy, peripheral blood B cell count less than 5 x 10\^9/L is allowed
• Biopsy proven Richter's transformation of the CLL
• NOTE: Previously treated patients including CLL therapy can be enrolled. If Richter's transformation (RT) developed from prior untreated CLL and has not received any RT directed therapy, then patient is not eligible
• Richter patients with prior or concurrent CLL diagnosis and do not have other option for standard therapy per treating physician's discretion
• Measurable disease can be detected in positron emission tomography (PET) or computed tomography (CT) (>= 1 cm in diameter)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
• Absolute neutrophil count >= 0.7 x 10\^9/L unless marrow was involved by CLL or RT, then absolute neutrophil count (ANC) >= 0.3 x 10\^9/L (=< 14 days prior to registration)
• Platelet count >= 40 x 10\^9/L unless marrow was involved by CLL or RT, then platelet >= 30 x 10\^9/L without transfusion =< 1 week prior to study registration (=< 14 days prior to registration)
• Hemoglobin (Hgb) >= 8 unless marrow was involved by CLL or RT, then Hgb >= 7 without transfusion =< 1 week prior to study registration (=< 14 days prior to registration)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) unless due to confirmed Gilbert's disease (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician (=< 14 days prior to registration)
• Note: If total bilirubin is > 1.5 x ULN, a direct bilirubin should be performed and must be =< upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X ULN unless liver metastases are present, in which case it must be =< 5 x ULN (=< 14 days prior to registration)
• Calculated creatinine clearance of > 30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) (=< 14 days prior to registration)
• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
• NOTE: The following restrictions apply while the patient is receiving study treatment and for the specified times before and after:

You may not qualify if…

• Any of the following uncontrolled intercurrent illness:
• Clinically significant cardiovascular disease such as:
• Symptomatic arrhythmias
• Congestive heart failure
• Myocardial infarction =< 3 months prior to registration
• Any class 3 or 4 cardiac disease as defined by the New York Heart Association functional classification
• Uncontrolled hypertension
• Unstable angina pectoris
• Note: Subjects with controlled, asymptomatic atrial fibrillation can enroll on study
• Serious chronic gastrointestinal conditions associated with diarrhea
• History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)
• History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
• History of bleeding diathesis (e.g., hemophilia, von Willebrand disease)
• Active uncontrolled infection (e.g., bacterial, viral or fungal, including subjects with positive cytomegalovirus [CMV] deoxyribonucleic acid [DNA] polymerase chain reaction [PCR]) requiring systemic therapy. NOTE: When the infection is controlled with systemic therapy, patients are permitted for this study
• Active tuberculosis infection (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice)
• Known human immunodeficiency virus (HIV/acquired immunodeficiency syndrome [AIDS]) infection as further severe immunosuppression with this regimen may occur
• Hepatitis B or C serologic status:
• Hepatitis B surface antigen and hepatitis B PCR positive will be excluded
• Hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative, and hepatitis B PCR positive will be excluded
• These above patients once treated for hepatitis B and became hepatitis B PCR negative, they will be eligible
• Hepatitis C PCR positive will be excluded. Once treated and hepatitis C PCR negative will be eligible
• NOTE: Once patients with active hepatitis treated with effective therapy and adequate disease control, they will be allowed for participation
• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
• Pregnant women
• Nursing women

Where it is running

• Mayo Clinic in Rochester — Rochester, Minnesota, United States (enrolling)
• Stanford Cancer Institute Palo Alto — Palo Alto, California, United States
• Washington University School of Medicine — St Louis, Missouri, United States

Full record on ClinicalTrials.gov

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