We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study Evaluating the Efficacy and Safety of Cevostamab in Prior B Cell Maturation Antigen (BCMA)-Exposed Participants With Relapsed/Refractory Multiple Myeloma (CAMMA 2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05535244
Recruitment Status : Recruiting
First Posted : September 10, 2022
Last Update Posted : November 15, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This study will evaluate the efficacy, safety, and pharmacokinetics of cevostamab in participants with refractory multiple myeloma (R/R MM) via intravenous (IV) infusion.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Cevostamab Drug: Tocilizumab Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-Label, Multi-Cohort Study to Evaluate the Efficacy and Safety of Cevostamab in Prior B Cell Maturation Antigen-Exposed Patients With Relapsed/Refractory Multiple Myeloma
Actual Study Start Date : October 18, 2022
Estimated Primary Completion Date : November 16, 2026
Estimated Study Completion Date : November 16, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Cohort A1: Prior BCMA antibody-drug conjugate (ADC) or chimeric antigen receptor T (CAR-T)
Participants in Cohort A1 will be treated at the double step-up split dosing regimen.
Drug: Cevostamab
Cevostamab will be administered by IV infusion in 21-day cycles.

Drug: Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.

Experimental: Cohort A2: Prior BCMA Bispecific
Participants enrolled into exploratory Cohort A2 will receive the same dosing regimen as Cohort A1.
Drug: Cevostamab
Cevostamab will be administered by IV infusion in 21-day cycles.

Drug: Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.

Experimental: Cohort B1: Prior BCMA ADC or CAR-T
Participants enrolled in expansion Cohort B1, will be given cevostamab at the recommended Phase 2 dose (RP2D).
Drug: Cevostamab
Cevostamab will be administered by IV infusion in 21-day cycles.

Drug: Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.

Experimental: Cohort B2: Prior BCMA Bispecific
Expansion Cohort B2 will be opened, after the intiial results from Cohort A2, at the same dose as per Cohort B1.
Drug: Cevostamab
Cevostamab will be administered by IV infusion in 21-day cycles.

Drug: Tocilizumab
Tocilizumab will be administered for the treatment of cytokine release syndrome (CRS) when necessary.




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Baseline up to approximately 2 years ]
  2. Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 2 years ]

Secondary Outcome Measures :
  1. ORR [ Time Frame: Baseline up to approximately 2 years ]
  2. Duration of Response (DOR) [ Time Frame: Baseline up to approximately 2 years ]
  3. Rate of Complete Response (CR) or Better [ Time Frame: Baseline up to approximately 2 years ]
  4. Rate of Very Good Partial Response (VGPR) or Better [ Time Frame: Baseline up to approximately 2 years ]
  5. Overall Survival (OS) [ Time Frame: Baseline up until death from any cause (up to approximately 2 years) ]
  6. Progression-free Survival (PFS) [ Time Frame: Baseline up to approximately 2 years ]
  7. Time to First Response (for Participants who Achieve an Objective Response) [ Time Frame: Baseline up to approximately 2 years ]
  8. Time to Best Response (for Participants who Achieve an Objective Response) [ Time Frame: Baseline up to approximately 2 years ]
  9. Minimal Residual Disease (MRD) Negative Rate [ Time Frame: Baseline up to approximately 2 years ]
  10. Percentage of Participants Experiencing a Clinically Meaningful Improvement in the Fatigue Domain of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core-30 Questionnaire (QLQ-C30) and EORTC QLQ-MY20 [ Time Frame: Baseline up to approximately 2 years ]
  11. Time to Deterioration in the Fatigue Domain of the EORTC QLQ-C30 and/or Disease Symptoms Domain of the EORTC QLQ-MY20 [ Time Frame: Baseline up to approximately 2 years ]
  12. Serum Concentration of Cevostamab at Specified Timepoints [ Time Frame: At Cycles 1, 2, 3, 4, 6, 8 and every other cycle until the end of treatment up to approximately 2 years. Each cycle is 21-days. ]
  13. Number of Anti-drug Antibody (ADAs) Against Cevostamab at Baseline [ Time Frame: Baseline ]
  14. Percentage of Participants with ADAs Against Cevostamab During the Study [ Time Frame: Up to approximately 2 years ]
  15. Cytokine Release Syndrome (CRS) Following Administration of Tocilizumab [ Time Frame: Baseline up to approximately 2 years ]
  16. Relationship Between Serum Concentration of Cevostamab and Cytokine Release [ Time Frame: Baseline up to approximately 2 years ]
  17. Relationship Between Serum Concentration of Cevostamab and T Cell Number [ Time Frame: Baseline up to approximately 2 years ]
  18. Relationship Between Serum Concentration of Cevostamab and T-cell Activation State [ Time Frame: Baseline up to approximately 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented diagnosis of MM based on standard International Myeloma Working Group (IMWG) criteria
  • Evidence of progressive disease based on investigators determination of response by IMWG criteria on or after their last dosing regimen
  • Prior BCMA ADC or CAR-T Cohort: participants who have received a BCMA-targeted CAR-T or ADC therapy and are triple-class refractory
  • Prior BCMA Bispecific Cohort: participants who have received a BCMA-targeting T-cell-dependent bispecific (TDB) antibody and are triple-class refractory
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Life expectancy is at least 12 weeks
  • Agreement to protocol-specified assessments, including bone marrow biopsy and aspirate samples as detailed in the protocol
  • Resolution of AEs from prior anti-cancer therapy to Grade =< 1
  • For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for at least 2 months after the final dose of cevostamab and for 3 months after the last dose of tocilizumab was administered
  • For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for at least 2 months after the final dose of cevostamab or tocilizumab (if applicable) to avoid exposing the embryo

Exclusion Criteria:

  • Inability to comply with protocol-mandated hospitalization
  • Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 3 months after the final dose of cevostamab or tocilizumab
  • Prior treatment with cevostamab or another agent with the same target
  • Prior BCMA ADC or CAR-T Cohort: prior treatment with any TDB antibody
  • Prior use of any monoclonal antibody (mAb), radioimmunoconjugate, or ADC as anti-cancer therapy within 4 weeks before first study treatment, except for the use of non-myeloma therapy
  • Prior treatment with systemic immunotherapeutic agents, including but not limited to, cytokine therapy and anti- Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), anti- Programmed cell death protein 1 (PD-1), and anti- Programmed death-ligand 1 (PD-L1) therapeutic antibodies within 12 weeks or 5 half-lives of the drug, whichever is shorter, before first study treatment
  • Prior treatment with CAR-T cell therapy within 12 weeks before first cevostamab infusion
  • Known treatment-related, immune-mediated adverse events associated with prior checkpoint inhibitors
  • Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other anti-cancer agent within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first study treatment
  • Autologous stem cell transplantation (SCT) within 100 days prior to first study treatment
  • Prior allogeneic SCT
  • Circulating plasma cell count exceeding 500/ microliter (µL) or 5% of the peripheral blood white cells
  • Prior solid organ transplantation
  • History of autoimmune disease
  • History of confirmed progressive multifocal leukoencephalopathy
  • History of severe allergic or anaphylactic reactions to mAb therapy
  • Known history of amyloidosis
  • Lesions in proximity of vital organs that may develop sudden decompensation/deterioration in the setting of a tumor flare
  • History of other malignancy within 2 years prior to screening, except those with negligible risk of metastasis or death, such as ductal carcinoma in situ not requiring chemotherapy, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, low-grade, localized prostate cancer not requiring treatment or appropriately treated Stage I uterine cancer
  • Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, neurodegenerative disease, or CNS involvement by MM
  • Significant cardiovascular disease that may limit a potential participant's ability to adequately respond to a cytokine release syndrome (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 (intravenous) antibiotics or antivirals for coronavirus disease 2019 (COVID-19) where the last dose of treatment was given within 14 days prior to first study treatment
  • Known or suspected chronic active Epstein-Barr virus (EBV) infection
  • Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
  • Recent major surgery within 4 weeks prior to first study treatment
  • Positive serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection
  • Acute or chronic hepatitis C virus (HCV) infection
  • Known history of human immunodeficiency virus (HIV) seropositivity
  • Administration of a live, attenuated vaccine within 4 weeks before first study treatment or anticipation that such a live attenuated vaccine will be required during the study
  • Treatment with systemic immunosuppressive medications, with the exception of corticosteroid treatment <= 10 mg/day prednisone or equivalent, within 2 weeks prior to first study treatment
  • History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05535244


Contacts
Layout table for location contacts
Contact: Reference Study ID Number: CO43476 https://forpatients.roche.com 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
Layout table for location information
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Tennessee
Tennessee Onc., PLLC - SCRI Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Methodist Hospital Recruiting
San Antonio, Texas, United States, 78229
Belgium
UZ Leuven Gasthuisberg Recruiting
Leuven, Belgium, 3000
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT05535244    
Other Study ID Numbers: CO43476
2021-006816-10 ( EudraCT Number )
First Posted: September 10, 2022    Key Record Dates
Last Update Posted: November 15, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases