A Study Evaluating the Safety and Efficacy of Multiple Treatments in Participants With Multiple Myeloma
NCT ID: NCT05583617
Last Updated: 2025-11-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1/PHASE2
200 participants
INTERVENTIONAL
2023-11-14
2028-07-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
This substudy will explore the combination of cevostamab and lenalidomide as post-transplant maintenance therapy in participants with MM with high-risk cytogenetic features who experienced at least a partial response (PR) after induction.
Cevostamab + Iberdomide SS4 (CHAWLA):
This substudy will evaluate the safety, tolerability, PK, and pharmacodynamics of the combination of cevostamab and iberdomide in participants with R/R MM who have received at least three prior lines of therapy, including a PI, an IMiD, and an anti-CD38 monoclonal antibody.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Substudy 2: Dose Escalation and Expansion
In the pre-phase, participants will receive 2 step-up doses and a target dose of cevostamab. The step-up dose will be given on Day(D)1 and D4. The target dose will be given on D8. Subsequently the target dose will be administered on D1 and D15 for cycles 1-6 and D1 of cycle 7 onwards. Each cycle is 28 days. Lenalidomide will be administered by mouth (PO) on a 28-day cycle.
During the dose expansion phase, cevostamab will be administered following the same dosing schedule as the dose escalation phase. The target dose will be determined after the escalation phase. Lenalidomide will be administered PO on a 28-day cycle.
Enrollment for Substudy 2 has closed.
Cevostamab
Substudy 2: Cevostamab will be administered intravenously (IV) on a 28-day cycle, up to a total of 13 cycles.
Substudy 4: Cevostamab will be administered by IV on a 21-day cycle, up to a total of 17 cycles.
Lenalidomide
Lenalidomide will be administered PO on days 1-21 of a 28-day cycle.
Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
Substudy 4: Dose Escalation and Expansion
In the pre-phase, participants will receive 2 step-up doses and a target dose of cevostamab. The step-up dose will be given on D1 and D4. The target dose will be given on D8. Subsequently the target dose will be administered on D1 of each cycle, every 3 weeks (Q3W). Each cycle is 21 days. Iberdomide will be administered PO on a 21-day cycle.
During the dose expansion phase, cevostamab will be administered following the same dosing schedule as the dose escalation phase. The target dose will be determined after the escalation phase. Iberdomide will be administered PO on a 21-day cycle.
Cevostamab
Substudy 2: Cevostamab will be administered intravenously (IV) on a 28-day cycle, up to a total of 13 cycles.
Substudy 4: Cevostamab will be administered by IV on a 21-day cycle, up to a total of 17 cycles.
Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
Iberdomide
Iberdomide will be administered PO on days 1-14 of a 21-day cycle.
Dexamethasone
Dexamethasone will be administered on Days 2 and 8 of Cycles 1-3.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Cevostamab
Substudy 2: Cevostamab will be administered intravenously (IV) on a 28-day cycle, up to a total of 13 cycles.
Substudy 4: Cevostamab will be administered by IV on a 21-day cycle, up to a total of 17 cycles.
Lenalidomide
Lenalidomide will be administered PO on days 1-21 of a 28-day cycle.
Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.
Iberdomide
Iberdomide will be administered PO on days 1-14 of a 21-day cycle.
Dexamethasone
Dexamethasone will be administered on Days 2 and 8 of Cycles 1-3.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Eastern Cooperative Oncology Group Performance Status of 0, or 1, or 2
* Resolution of AEs from prior anti-cancer therapy to Grade \<=1
* Agreement to undergo scheduled assessments and procedures
* Completion of planned induction therapy and achievement of at least a partial response (PR)
* Autologous Stem Cell Transplant (SCT) within 100 days prior to first study treatment and the absence of progressive disease
* Cytogenetic high-risk features at diagnosis
* Treatment with any investigational medicinal products, systemic cancer therapies, immunotherapies received previously in CO43923 (any arms) within 5 half-lives or 3 weeks whichever is the shortest
* Agreement to comply with all local requirements of the lenalidomide risk minimization plan, which includes the global pregnancy prevention program
* For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom even if they have had a prior vasectomy, and agreement to refrain from donating sperm
* Previously exposed to at least a PI, an IMiD, and an anti-CD38 antibody for the treatment of R/R MM for whom no suitable SOC therapy options are available
Exclusion Criteria
* History of confirmed progressive multifocal leukoencephalopathy
* History of other malignancy within 2 years prior to screening
* Current or past history of central nervous system (CNS) disease
* Significant cardiovascular disease that may limit a participant's ability to adequately respond to a CRS event
* Symptomatic active pulmonary disease or requiring supplemental oxygen
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment, or any major episode of infection requiring treatment with IV antibiotics where the last dose of IV antibiotics was given within 14 days prior to first study treatment
* Known or suspected chronic active Epstein-Barr virus (EBV) infection
* Positive serologic or PCR test results for acute or chronic hepatitis B virus (HBV) infection
* Acute or chronic hepatitis C virus (HCV) infection
* Known history of HIV seropositivity
* Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation that such a live, attenuated vaccine will be required during the study
* Any medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results
* Hypersensitivity reactions to lenalidomide or other immunomodulatory drugs
* Harbor lesions at proximity of vital organs that may develop sudden decompensation/deterioration in the setting of a tumor flare
* Prior treatment with any investigational medicinal product, systemic cancer therapy, or immunotherapies in any arm of study CO43923 within 5 half-lives or 3 weeks, whichever is shorter
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antimicrobials where the last dose of IV antimicrobial was given within 14 days prior to first study treatment
* History of erythema multiforme, Grade \>=3 rash, or blistering following prior treatment with immunomodulatory derivatives
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study treatment Exlcusion Criteria Applicable to SS2 and SS4
* History of autoimmune disease
* Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
* Received a cumulative dose of corticosteroids equivalent to \>=140 mg of prednisone within the 14-day period before the first dose of the study drug (does not include pretreatment medication)
* Active symptomatic COVID-19 infection at study enrollment or requiring treatment with IV antiviral where the last dose of IV antiviral treatment was given within 14 days prior to first study treatment. Participants with active COVID-19 infection must have clinical recovery and two negative antigen tests at least 24 hours apart prior to first study treatment.
* Positive and quantifiable EBV PCR or CMV PCR prior to first study treatment
* Treatment with any investigational medicinal products, systemic cancer therapies, immunotherapies within 5 half-lives or 12 weeks before starting pre-phase
* History of anaphylaxis or hypersensitivity, including \>=Grade 3 rash, during prior treatment with IMiDs, dexamethasone, any CELMoDs, or the excipients contained in the formulations
* Known anaphylaxis, allergies, hypersensitivity, or intolerance to boron or mannitol, hyaluronidase, sorbitol, corticosteroids, monoclonal antibodies (or recombinant antibody-related fusion proteins), or human proteins, CRBN modulating agents or their excipients, or known sensitivity to mammalian-derived products
* Administration of strong CYP3A modulators; administration of proton-pump inhibitors within 2 weeks of starting study treatment
* Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment
* Concurrent administration of a strong inhibitor, modulator or inducer of cytochrome P450 (CYP3A4/5) (including within 14 days of initiating study treatment)
* History of malignancies, other than MM, unless the subject has been free of the disease for \>=5 years
* Peripheral neuropathy \>Grade 2
* Prior treatment with cevostamab or another agent targeting FcRH5 or iberdomide
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study treatment
* History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug rash with eosinophilia and systemic symptoms
* Treatment with systemic immunosuppressive medications
* Prior treatment with CAR T-cell therapy (autologous or allogeneic) within 12 weeks before starting pre-phase
* Autologous SCT within 100 days prior to starting pre-phase
* Prior allogeneic SCT
* Plasmacytoma in proximity of vital organs that may develop sudden decompensation/deterioration in the setting of a tumor flare
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Hoffmann-La Roche
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Prince of Wales Hospital
Randwick, New South Wales, Australia
St Vincent's Hospital Melbourne
Fitzroy, Victoria, Australia
CHU Lyon Sud - Service Hématologie
Pierre-Bénite, , France
IUCT Oncopole
Toulouse, , France
Hopital Bretonneau
Tours, , France
IGR
Villejuif, , France
Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II
Hamburg, , Germany
Universitätsklinikum Leipzig - Klinik und Poliklinik für Hämatologie
Leipzig, , Germany
Uniwersyteckie Centrum Kliniczne
Gda?sk, , Poland
Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
Olsztyn, , Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
Późna, , Poland
Severance Hospital, Yonsei University Health System
Seoul, , South Korea
Samsung Medical Center
Seoul, , South Korea
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain
Fundacion Jimenez Diaz
Madrid, , Spain
Hospital Clinico Universitario de Valencia
Valencia, , Spain
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Reference Study ID Number: CO43923 https://forpatients.roche.com/
Role: CONTACT
Phone: 888-662-6728 (U.S. and Canada)
Email: [email protected]
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CO43923
Identifier Type: -
Identifier Source: org_study_id
2021-005918-34
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2023-504484-16-00
Identifier Type: CTIS
Identifier Source: secondary_id