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Zanubrutinib and Lisocabtagene Maraleucel for the Treatment of Richter's Syndrome

ConditionsRecurrent Transformed Chronic Lymphocytic LeukemiaRefractory Transformed Chronic Lymphocytic LeukemiaTransformed Chronic Lymphocytic Leukemia to Diffuse Large B-Cell LymphomaRecurrent Transformed B-Cell Non-Hodgkin LymphomaRecurrent Transformed Non-Hodgkin LymphomaRefractory Transformed Non-Hodgkin LymphomaRefractory Transformed B-cell Non-Hodgkin LymphomaRefractory Transformed
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAseel Alsouqi

About this trial

This phase II trial tests how well zanubrutinib and lisocabtagene maraleucel (liso-cel) work together in treating patients with Richter's syndrome that has come back (recurrent) or does not respond to treatment (refractory). Richter's syndrome occurs when chronic lymphocytic leukemia and/or small lymphocytic leukemia transforms into an aggressive lymphoma, which is a cancer of the lymph nodes. Zanubrutinib is a class of medication called a kinase inhibitor. These drugs work by preventing the action of abnormal proteins that tell cancer cells to multiply, which helps stop the spread of cancer. Liso-cel is a type of treatment known as chimeric antigen receptor (CAR) T cell therapy. CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving zanubrutinib and liso-cell together may kill more cancer cells in patients with recurrent or refractory Richter's syndrome.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Diagnosis of RS - occurrence of diffuse large B-cell lymphoma (DLBCL) in patients with antecedent or concurrent CLL/SLL (CLL/SLL diagnosis per IWCLL 2018 criteria).

Participants must have undergone >= 1 prior systemic therapeutic regimen administered for >= 1 cycle for either CLL or RS, and have had either documented disease progression to the most recent treatment regimen, or refractory disease. OR

Developed RS while receiving treatment for CLL

Age >= 18 years

Disqualifiers

A history of treatment including any of the following: prior CD19 directed therapy, treatment with alemtuzumab within 6 months before enrollment, prior allogeneic hematopoietic stem cell transplant (SCT) or donor lymphocyte infusion (DLI) within 2 months prior to enrollment

Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent

Inadequate recovery from adverse events related to prior therapy to grade =< 1 (excluding grade 2 alopecia, neuropathy, and hypertension)

Is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication

Trial design

Design model

Single group

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of blood samples

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo BM biopsy

  • Computed Tomography

    Procedure/Surgery

    Undergo CT and/or PET/CT

  • Cyclophosphamide

    Drug

    Given IV

  • Fludarabine

    Drug

    Given IV

  • Leukapheresis

    Procedure/Surgery

    Given IV

  • Lisocabtagene Maraleucel

    Biological/Vaccine

    Given IV

  • Lymph Node Biopsy

    Procedure/Surgery

    Undergo lymph node biopsy

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET/CT

  • Zanubrutinib

    Drug

    Given PO

Treatment groups

24 Participants
are divided into 1 treatment group
Group A: Treatment (zanubrutinib, liso-cel)Experimental treatment 10 interventions

Trial outcomes

Primary outcomes

1

Overall response rate

Overall response rate (ORR) will be defined as the proportion of patients achieving a complete or partial response divided by the number of efficacy-evaluable patients according to the Revised Response Criteria for Malignant Lymphoma. Response will be assessed using Lugano criteria 2014. ORR will be reported with two-sided 95% and 80% binomial exact confidence intervals.

Time frame
At 90 days after lisocabtagene maraleucel (liso-cel) infusion

Secondary outcomes

1

Incidence of adverse events

Adverse event data will be collected on all patients who receive at least one dose of study drug(s). Non-hematologic adverse events (AEs) will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Hematologic AEs will be graded according to chronic lymphocytic leukemia-specific criteria described in the International Workshop on Chronic Lymphocytic Leukemia 2018 guidelines.

Time frame
Up to 2 years
2

Progression free survival

Will be estimated using Kaplan-Meier methodology. Median estimates and estimates at clinically meaningful time points will be reported with 95% confidence intervals.

Time frame
Time from liso-cel infusion until documented disease progression, or death from any cause, whichever occurs first, assessed up to 2 years
3

Overall survival

Will be estimated using Kaplan-Meier methodology. Median estimates and estimates at clinically meaningful time points will be reported with 95% confidence intervals.

Time frame
Time from liso-cel infusion until death from any cause, assessed up to 2 years
4

Duration of response

Will be estimated using Kaplan-Meier methodology. Median estimates and estimates at clinically meaningful time points will be reported with 95% confidence intervals.

Time frame
Time from the first tumor assessment that supports response to the time of confirmed disease progression or death due to any cause, whichever occurs first, assessed up to 2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Aseel Alsouqi

Lead sponsor

Ohio State University Comprehensive Cancer Center

Sponsor institution

BeOne Medicines

Collaborator

Source ClinicalTrials.gov
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