Chronic Lymphocytic Leukemia or Small Lymphocytic LymphomaPhase 1NCT05091424
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
A Phase 1 study testing Mosunetuzumab, Tocilizumab and Venetoclax in people with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma, run by Hoffmann-La Roche at 31 sites in 10 countries.
Trial summary
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) or small lymphocytic lymphoma (SLL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
- What is being tested?
- Mosunetuzumab, Tocilizumab and Venetoclax
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 332 participants
- Where
- 31 sitesin 10 countries
- Study dates
- 7 Mar 2022to 10 Feb 2032
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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 up to three cycles of mosunetuzumab administration
- Non-US participants only
Who cannot join
- 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)
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- 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
Trial locations and contacts
31 sites in 10 countries. Contact the study team or a site near you to ask about taking part.
Reference Study ID Number: BO43243 https://forpatients.roche.com/ No attachments to email below. contact
Fastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry contact
31 sites in 10 countries
United States5 sites, 3 recruiting
- Recruiting
The James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210
- Withdrawn
Uni of Texas - Md Anderson Cancer Center
Houston, Texas, 77030
- Withdrawn
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
- Recruiting
Mayo Clinic Rochester
Rochester, Minnesota, 55902
- Recruiting
Huntsman Cancer Institute at The University of Utah
Salt Lake City, Utah, 84112
China4 sites, 4 recruiting
- Recruiting
Peking University People's Hospital
Beijing, 100044
- Recruiting
Southern Medical University Nanfang Hospital
Guangzhou, 510515
- Recruiting
The First Affiliated Hospital of Nanchang University
Nanchang
- Recruiting
Tianjin Institute of Hematology & Blood Diseases Hospital
Tianjin, 301600
Italy4 sites, 4 recruiting
- Recruiting
A.O. Spedali Civili Di Brescia-P.O. Spedali Civili
Brescia, Lombardy, 25123
- Recruiting
Osp. San Raffaele
Milan, Lombardy, 20132
- Recruiting
Asst Grande Ospedale Metropolitano Niguarda
Milan, Lombardy, 20162
- Recruiting
Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia
Sant'Andrea Delle Fratte (PG), Umbria, 06132
Australia3 sites, 2 recruiting
- Completed
Peter MacCallum Cancer Center
East Melbourne, Victoria, 3002
- Recruiting
Monash Medical Centre
Melbourne, Victoria, 3168
- Recruiting
Princess Alexandra Hospital Woolloongabba
Woolloongabba, Queensland, 4102
Germany3 sites, 1 recruiting
- Recruiting
Universitätsklinikum Augsburg
Augsburg, 86156
- Withdrawn
Uniklinik Koln
Cologne, 50937
- Withdrawn
Universitätsklinikum Ulm
Ulm, 89081
Poland3 sites, 3 recruiting
- Recruiting
Uniwersyteckie Centrum Kliniczne
Gda?sk, 80-214
- Recruiting
PRATIA MCM Kraków
Krakow, 30-727
- Recruiting
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
Wroc?aw, 50-367
South Korea3 sites, 3 recruiting
- Recruiting
Seoul National University Hospital
Seoul, 03080
- Recruiting
Seoul St Mary's Hospital
Seoul, 06591
- Recruiting
Yeouido St. Mary's Hospital
Seoul, 07345
France2 sites
- Withdrawn
Chu de Clermont Ferrand
Clermont-Ferrand, 63003
- Withdrawn
IUCT Oncopole
Toulouse, 31059
Spain2 sites, 2 recruiting
- Recruiting
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, 08035
United Kingdom2 sites, 2 recruiting
- Recruiting
Christie Hospital NHS Trust
Manchester, M20 4BX
- Recruiting
Churchill Hospital
Oxford, OX3 7LE
About this study
Official title: A Phase IB Open-Label, Multicenter Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Mosunetuzumab and a Combined Regimen of Mosunetuzumab and Venetoclax in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
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) or small lymphocytic lymphoma (SLL). 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 three 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, compared to standard-of-care rituximab plus venetoclax.
- Being tested
- Mosunetuzumab, Tocilizumab, Venetoclax, Rituximab
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MosunetuzumabDrug
Also called Lunsumio
Participants will receive subcutaneous (SC) mosunetuzumab.
TocilizumabDrug
Participants will receive intravenous (IV) tocilizumab as needed for cytokine release syndrome (CRS) events.
VenetoclaxDrug
Also called Venclyxto, Venclexta
Participants will receive daily oral venetoclax.
RituximabDrug
Participants will receive IV rituximab as per protocol.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Participants with R/R CLL/SLL after two prior lines of therapy and who have had prior exposure to BTKi and/or venetoclax will receive mosunetuzumab subcutaneous (SC) monotherapy Receives: Drug: Mosunetuzumab; Drug: Tocilizumab |
| Arm B | Experimental | Participants with R/R CLL/SLL after two or more 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 up to the first three cycles of mosunetuzumab SC. NOTE: Arm B is closed to enrollment. Receives: Drug: Mosunetuzumab; Drug: Tocilizumab |
| Arm C (non-US participants only) | Experimental | Participants with R/R CLL/SLL after two or more prior lines of therapy and who have had prior exposure to BTKi and/or venetoclax will receive mosunetuzumab SC with venetoclax during dose escalation phase. Participants with R/R CLL/SLL after at least one prior line of therapy must have prior exposure to BTKi and/or venetoclax and >12 months since last venetoclax exposure will receive mosunetuzumab SC with venetoclax during the dose expansion phase. During the dose expansion phase, a control cohort receiving the standard-of-care regimen of rituximab plus venetoclax has been added (this arm is open only to participants outside of the US). Receives: Drug: Mosunetuzumab; Drug: Tocilizumab; Drug: Venetoclax; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Dose-Limiting Toxicities (DLTs)
Measured: From the first administration of mosunetuzumab until 21 days after the final mosunetuzumab step-up dose for Arms A, B, and C (up to 3 months)
Objective Response Rate (ORR) During Dose Expansion Phase
Measured: Up to 8-12 weeks after the last dose of study drug
Secondary outcomes (15)
Objective Response Rate (ORR) During Dose Escalation Phase
Measured: Up to 8-12 weeks after the last dose of study drug
Progression-Free Survival (PFS)
Measured: From the first study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 12 months (Arms A and B) or 24 months (Arm C))
Overall Survival (OS)
Measured: From the first dose of study drug to death from any cause (up to approximately 12 months (Arms A and B) or 24 months (Arm C))
Event-Free Survival (EFS)
Measured: Between the date of the first study treatment to the date of disease progression/relapse, death, or start of new anti-leukemic therapy, whichever occurs first (up to approximately 12 months (Arms A and B) or 24 months (Arm C))
Complete Response (CR) Rate
Measured: Up to 8-12 weeks after the last dose of study drug
Duration of Response (DOR)
Measured: From the first occurrence of a documented objective response to disease progression by iwCLL 2018 criteria or death from any cause (up to approximately 12 months (Arms A and B) or 24 months (Arm C))
Duration of Complete Response (DOCR)
Measured: From the first occurrence of a documented complete response to disease progression by iwCLL 2018 criteria or death from any cause (up to approximately 12 months (Arms A and B) or 24 months (Arm C))
Percentage of Participants with Adverse Events (AEs)
Measured: Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Maximum Serum Concentration (Cmax) of Mosunetuzumab SC
Measured: Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Minimum Serum Concentration (Cmin) of Mosunetuzumab SC
Measured: Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Time to Maximum Concentration (Tmax) of Mosunetuzumab SC
Measured: Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Maximum Serum Concentration (Cmax) of BTKi or Venetoclax
Measured: Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Minimum Serum Concentration (Cmin) of BTKi or Venetoclax
Measured: Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Time to Maximum Concentration (Tmax) of BTKi or Venetoclax
Measured: Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Incidence of Anti-Drug Antibodies (ADAs)
Measured: Baseline through end of study (up to approximately 12 months for Arms A and B, or 24 months for Arm C)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2021
- Study start7 Mar 2022
- Primary completion10 Feb 2031 (estimated)
- Study completion10 Feb 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic Leukemia or Small Lymphocytic LymphomaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 332 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05091424
- Sponsor's protocol ID
- BO43243
- Status last verified
- Oct 2026
- First submitted
- 12 Oct 2021
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No