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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05091424




Registration number
NCT05091424
Ethics application status
Date submitted
12/10/2021
Date registered
25/10/2021
Date last updated
3/05/2024

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
BO43243
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mosunetuzumab
Treatment: Drugs - Tocilizumab
Treatment: Drugs - Venetoclax

Experimental: 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

Experimental: 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

Experimental: Arm C - 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


Treatment: Drugs: Mosunetuzumab
Participants will receive subcutaneous (SC) mosunetuzumab

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

Treatment: Drugs: Venetoclax
Participants will receive daily oral venetoclax
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of Dose-Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to 8-12 weeks after the last dose of study drug
Secondary outcome [2] 0 0
Minimal Residual Disease (MRD) Response Rate
Timepoint [2] 0 0
Up to 8-12 weeks after the last dose of study drug
Secondary outcome [3] 0 0
Progression-Free Survival (PFS)
Timepoint [3] 0 0
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))
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
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))
Secondary outcome [5] 0 0
Event-Free Survival (EFS)
Timepoint [5] 0 0
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))
Secondary outcome [6] 0 0
Complete Response (CR) Rate
Timepoint [6] 0 0
Up to 8-12 weeks after the last dose of study drug
Secondary outcome [7] 0 0
Duration of Response (DOR)
Timepoint [7] 0 0
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))
Secondary outcome [8] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [8] 0 0
Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Secondary outcome [9] 0 0
Maximum Serum Concentration (Cmax) of Mosunetuzumab SC
Timepoint [9] 0 0
Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Secondary outcome [10] 0 0
Minimum Serum Concentration (Cmin) of Mosunetuzumab SC
Timepoint [10] 0 0
Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Secondary outcome [11] 0 0
Time to Maximum Concentration (Tmax) of Mosunetuzumab SC
Timepoint [11] 0 0
Up to approximately 12 months (Arms A and B) or 24 months (Arm C)
Secondary outcome [12] 0 0
Incidence of Anti-Drug Antibodies (ADAs)
Timepoint [12] 0 0
Baseline through end of study (up to approximately 12 months for Arms A and B, or 24 months for Arm C)

Eligibility
Key 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

Inclusion Criteria Specific to Arm B:

- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Exclusion Criteria Specific to Arm C:

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/03/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
8/10/2029
Actual
Sample size
Target
137
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology - Woolloongabba
Recruitment hospital [2] 0 0
Monash Medical Centre; Haematology - Melbourne
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Center - North Melbourne
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
3168 - Melbourne
Recruitment postcode(s) [3] 0 0
3051 - North Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Minnesota
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
France
State/province [4] 0 0
Clermont-Ferrand
Country [5] 0 0
France
State/province [5] 0 0
Toulouse
Country [6] 0 0
Germany
State/province [6] 0 0
Augsburg
Country [7] 0 0
Germany
State/province [7] 0 0
Köln
Country [8] 0 0
Germany
State/province [8] 0 0
Ulm
Country [9] 0 0
Italy
State/province [9] 0 0
Lombardia
Country [10] 0 0
Italy
State/province [10] 0 0
Umbria
Country [11] 0 0
Spain
State/province [11] 0 0
Barcelona
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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). 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 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05091424
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: BO43243 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05091424