A Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Mosunetuzumab and a Combined Regimen of Mosunetuzumab and Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia

NCT ID: NCT05091424

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

137 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-07

Study Completion Date

2030-02-28

Brief Summary

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This study will assess the safety, tolerability, pharmaokinetics, and preliminary efficacy of mosunetuzumab (Lunsumio) monotherapy in participants with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL). This study will also allow participants who are currently progressing on a Bruton tyrosine kinase inhibitor (BTKi) and requiring salvage therapy as assessed by the treating physician to continue their BTKi throughout the screening period and for the first two cycles of mosunetuzumab. An additional arm (open to non-US participants only) has been added to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of mosunetuzumab in combination with venetoclax, a B-cell lymphoma 2 (BCL2) inhibitor.

Detailed Description

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Conditions

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Chronic Lymphocytic Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A

Participants with R/R CLL who have failed two prior lines of therapy and who have had prior exposure to BTKi and/or venetoclax will receive mosunetuzumab subcutaneous (SC) monotherapy

Group Type EXPERIMENTAL

Mosunetuzumab

Intervention Type DRUG

Participants will receive subcutaneous (SC) mosunetuzumab

Tocilizumab

Intervention Type DRUG

Participants will receive intravenous (IV) tocilizumab as needed for cytokine release syndrome (CRS) events.

Arm B

Participants with R/R CLL who have failed two prior lines of therapy, who are currently progressing on BTKi therapy, and who require salvage therapy as assessed by their treating physician will receive mosunetuzumab SC with BTKi overlap therapy for the first two cycles of mosunetuzumab SC

Group Type EXPERIMENTAL

Mosunetuzumab

Intervention Type DRUG

Participants will receive subcutaneous (SC) mosunetuzumab

Tocilizumab

Intervention Type DRUG

Participants will receive intravenous (IV) tocilizumab as needed for cytokine release syndrome (CRS) events.

Arm C (non-US participants only)

Participants with R/R CLL who have failed two prior lines of therapy and who have had prior exposure to BTKi and/or venetoclax will receive mosunetuzumab SC with venetoclax (this arm is open only to participants outside of the US)

Group Type EXPERIMENTAL

Mosunetuzumab

Intervention Type DRUG

Participants will receive subcutaneous (SC) mosunetuzumab

Tocilizumab

Intervention Type DRUG

Participants will receive intravenous (IV) tocilizumab as needed for cytokine release syndrome (CRS) events.

Venetoclax

Intervention Type DRUG

Participants will receive daily oral venetoclax

Interventions

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Mosunetuzumab

Participants will receive subcutaneous (SC) mosunetuzumab

Intervention Type DRUG

Tocilizumab

Participants will receive intravenous (IV) tocilizumab as needed for cytokine release syndrome (CRS) events.

Intervention Type DRUG

Venetoclax

Participants will receive daily oral venetoclax

Intervention Type DRUG

Other Intervention Names

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Lunsumio Venclyxto Venclexta

Eligibility Criteria

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Inclusion Criteria

* Have a diagnosis of CLL requiring treatment according to the International Workshop on CLL (iwCLL) criteria (Hallek et al 2018)
* Eastern Cooperative Oncology Group (ECOG) performance score (PS) of ≤ 2
* Adequate bone marrow (BM) function independent of growth factor or transfusion support, within 2 weeks of screening, at screening as defined by the protocol unless cytopenia is clearly due to marrow involvement of CLL
* Adequate liver function unless directly attributable to the participant's CLL
* Life expectancy \> 6 months
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \< 1% per year, and agreement to refrain from donating eggs during the treatment period and for at least 3 months after the last dose of mosunetuzumab and 3 months after the last dose of tocilizumab (if applicable)
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm as defined by the protocol


* Participants must have been taking a BTKi for at least 12 months, have demonstrated evidence of progressive disease while receiving the BTKi and require additional salvage therapy as assessed by their treating physician. Participants should be able to continue their previously prescribed BTKi at a stable dose throughout the study screening period and for the first two cycles of mosunetuzumab administration


* Non-US participants only

Exclusion Criteria

* Pregnant or breastfeeding, or intending to become pregnant during the study or within 3 months after the final dose of mosunetuzumab and tocilizumab or within 30 days after the final dose of venetoclax (if applicable)
* Participants who have received any of the following treatments prior to study entry: treatment with mosunetuzumab or other CD20/CD3-directed bispecific antibodies; allogenic stem cell transplant
* Participants who have received any of the following treatments, whether investigational or approved, within the respective time periods prior to initiation of study treatment: radiotherapy within 2 weeks prior to the first dose of study treatment; autologous stem cell transplant within 100 days prior to first study treatment; CAR T-cell therapy within 30 days before first study treatment; prior use of any monoclonal antibodies, radioimmunoconjugates, or antibody-drug conjugates for anti-CLL treatment within 4 weeks before first dose of study treatment; systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to the first dose of study treatment; any other anti-cancer therapy, whether investigational or approved, including but not limited to chemotherapy within 4 weeks prior to initiation of study treatment (except for participants enrolled in Arm B, where overlapping therapy is permitted; other prior cancer immunotherapy not explicitly defined by the protocol is to be discussed with the medical monitor to determine eligibility
* Received a live, attenuated vaccine within 4 weeks before the first dose of study treatment, or in whom it is anticipated that such a vaccine will be required during the study period or within 5 months after the final dose of study treatment
* Transformation of CLL to aggressive non-Hodgkin's lymphoma (NHL)
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
* Contraindication to tocilizumab
* History of prior malignancy except for conditions defined by the protocol
* Participants with infections requiring intravenous (IV) treatment with antibiotics or hospitalization within the last 4 weeks prior to enrollment or known active bacterial, viral (including SARS-CoV-2), fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment
* Evidence of any significant concomitant disease that could affect compliance with the protocol or interpretation of results
* Recent major surgery within 4 weeks prior to first study treatment administration, with the exception of protocol-mandated procedures (e.g., tumor biopsies and bone marrow biopsies)
* Positive SARS-CoV-2 test within 7 days prior to enrollment


* Have received venetoclax therapy within 12 months prior to first study treatment administration
* Participants with known infection with HIV or human T-cell leukemia virus 1 (HTLV1)
* HIV testing will be performed in countries where mandatory testing by health authorities is required
* HTLV testing is required in participants from endemic countries
* Participants with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
* Participants who have received the following: strong and moderate CYP3A inhibitors within 7 days prior to the initiation of study treatment; strong and moderate CYP3A inducers within 7 days prior to the initiation of study treatment; steroid therapy for anti-neoplastic intent with the exception of inhaled steroids for asthma, topical steroids, or replacement/stress corticosteroids within 7 days prior to the first dose of study drug administration
* Have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study drug and throughout venetoclax administration
* Inability to swallow a large number of tablets
* Malabsorption syndrome or other condition that precludes enteral route of administration
* Known allergy to both xanthine oxidase inhibitors and rasburicase
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status WITHDRAWN

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States

Site Status RECRUITING

Uni of Texas - Md Anderson Cancer Center

Houston, Texas, United States

Site Status WITHDRAWN

Huntsman Cancer Institute at The University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

Princess Alexandra Hospital Woolloongabba

Woolloongabba, Queensland, Australia

Site Status RECRUITING

Peter MacCallum Cancer Center

East Melbourne, Victoria, Australia

Site Status COMPLETED

Monash Medical Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Southern Medical University Nanfang Hospital

Guangzhou, , China

Site Status RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, , China

Site Status RECRUITING

Tianjin Institute of Hematology & Blood Diseases Hospital

Tianjin, , China

Site Status RECRUITING

Chu de Clermont Ferrand

Clermont-Ferrand, , France

Site Status WITHDRAWN

IUCT Oncopole

Toulouse, , France

Site Status WITHDRAWN

Universitätsklinikum Augsburg

Augsburg, , Germany

Site Status RECRUITING

Uniklinik Koln

Cologne, , Germany

Site Status WITHDRAWN

Universitätsklinikum Ulm

Ulm, , Germany

Site Status RECRUITING

A.O. Spedali Civili Di Brescia-P.O. Spedali Civili

Brescia, Lombardy, Italy

Site Status RECRUITING

Osp. San Raffaele

Milan, Lombardy, Italy

Site Status RECRUITING

Asst Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, Italy

Site Status COMPLETED

Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia

Sant'Andrea Delle Fratte (PG), Umbria, Italy

Site Status RECRUITING

Uniwersyteckie Centrum Kliniczne

Gda?sk, , Poland

Site Status RECRUITING

PRATIA MCM Kraków

Krakow, , Poland

Site Status RECRUITING

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroc?aw, , Poland

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Seoul St Mary's Hospital

Seoul, , South Korea

Site Status RECRUITING

Yeouido St. Mary's Hospital

Seoul, , South Korea

Site Status RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Christie Hospital NHS Trust

Manchester, , United Kingdom

Site Status RECRUITING

Churchill Hospital

Oxford, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia China France Germany Italy Poland South Korea Spain United Kingdom

Central Contacts

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Reference Study ID Number: BO43243 https://forpatients.roche.com/

Role: CONTACT

Phone: 888-662-6728

Email: [email protected]

Other Identifiers

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BO43243

Identifier Type: -

Identifier Source: org_study_id