A study to evaluate safety, pharmacokinetics, and activity of cevostamab in patients with relapsed or refractory multiple myeloma
- Conditions
- Multiple myeloma is a cancer that affects a type of white blood cell. Refractory means your cancer doesn't improve with treatment, or it stops responding to treatment.CancerRelapsed or refractory multiple myeloma
- Registration Number
- ISRCTN53331091
- Lead Sponsor
- Genentech Inc. c/o F.Hoffman-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 120
1. Age >= 18 years
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
3. Life expectancy of at least 12 weeks
4. Agreement to undergo scheduled assessments and procedures including bone marrow biopsy and aspirate samples
5. Resolution of adverse events from prior anti-cancer therapy to Grade <=1
6. Measurable disease
7. Adequate hepatic and hematologic function
8. For women of childbearing potential: agreement to remain abstinent or use contraception, during the treatment period (including treatment interruptions) and for at least 2 months after the last dose of cevostamab and at least 3 months after the last dose of tocilizumab was administered
9. For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm, during the treatment period, and for at least 2 months after the last dose of cevostamab or tocilizumab was administered to avoid exposing the embryo and sexual partner
Additional Arm A-Specific Inclusion Criteria
10. Diagnosis of R/R MM for which no established therapy for MM is appropriate and available, or intolerance to those established therapies
Additional Arm B-Specific Inclusion Criteria
11. For Cohort B1S: Patients with R/R MM who have received at least 2 prior lines of treatment
12. For Cohort B1E: Patients with R/R MM who have received at least 1 prior line of treatment
13. Agreement to comply with all local requirements of the pomalidomide pregnancy risk minimization plan
14. Agreement to avoid donating blood during the treatment period and for at least 4 weeks after the last dose of pomalidomide
15. For women of childbearing potential: agreement to remain abstinent or use two reliable methods of contraception starting at least 4 weeks prior to, during the treatment period, and for at least 4 weeks after the last dose of pomalidomide was administered
16. For men: agreement to remain abstinent or use a condom during the treatment period and for at least 4 weeks after the last dose of pomalidomide, and agreement to refrain from donating sperm during this same period
Additional Arm C-Specific Inclusion Criteria
17. For Cohort C1S: Patients with R/R MM who have received at least 2 prior lines of treatment
18. For Cohort C1E: Patients with R/R MM who have received at least 1 prior line of therapy
19. For women of childbearing potential: agreement to remain abstinent or use contraceptive methods during the treatment period and for at least 3 months after the last dose of daratumumab was administered
20. For men: agreement to remain abstinent or use a condom during the treatment period and for at least 3 months after the last dose of daratumumab was administered to avoid exposing the embryo, and agreement to refrain from donating sperm during this same period
1. Prior treatment with cevostamab or another agent targeting fragment crystallizable receptor-like 5 (FcRH5)
2. Inability to comply with protocol-mandated hospitalization and activities restrictions
3. Pregnant or breastfeeding, or intending to become pregnant during the study or within 2 months after the last dose of cevostamab or within 3 months after the last dose of tocilizumab
4. Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate as anti-cancer therapy within 4 weeks before first study treatment
5. Prior treatment with systemic immunotherapeutic agents within 12 weeks or 5 half-lives of the drug before first study treatment
6. Prior treatment with chimeric antigen receptor T (CAR T) cell therapy within 12 weeks before first study treatment
7. Known treatment-related, immune-mediated adverse events associated with prior checkpoint inhibitors
8. Treatment with radiotherapy within 4 weeks (systemic radiation) or 14 days (focal radiation) prior to first study treatment
9. Treatment with any chemotherapeutic agent or other anti-cancer agent within 4 weeks or 5 half-lives of the drug before first study treatment
10. Autologous stem cell transplant (SCT) within 100 days prior to first study treatment
11. Prior allogeneic SCT
12. Circulating plasma cell count exceeding 500/microliter or 5% of the peripheral blood white cells
13. Prior solid organ transplantation
14. History of autoimmune disease
15. History of confirmed progressive multifocal leukoencephalopathy
16. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
17. Known history of amyloidosis
18. Lesions in proximity of vital organs that may develop sudden decompensation/deterioration in the setting of a tumor flare
19. History of other malignancy within 2 years prior to screening
20. Current or past history of central nervous system (CNS) disease
21. Significant cardiovascular disease
22. Known history of Grade >=3 cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (ICANS) with prior bispecific therapies
23. Symptomatic active pulmonary disease or requiring supplemental oxygen
24. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
25. Known or suspected chronic active Epstein-Barr virus (EBV) infection
26. Recent major surgery within 4 weeks prior to first study treatment
27. Positive serologic or PCR test results for acute or chronic HBV infection
28. Acute or chronic hepatitis C virus (HCV) infection
29. Known history of HIV seropositivity
30. Administration of a live, attenuated vaccine within 4 weeks before first study treatment
31. Treatment with systemic immunosuppressive medications within 2 weeks prior to first study treatment
32. History of illicit drug or alcohol abuse within 12 months prior to screening
33. Any medical condition or abnormality in clinical laboratory tests that, in investigator’s judgement, precludes the patient’s safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of the results
Additional Arm B-Specific Exclusion Criteria
34. Pregnant or breastfeeding, or intending to become pregnant 4 weeks prior to initiation of study treatment, during the study, or within 4 weeks after the last dose of pomalidomide
35. History of erythema multiforme, Grade >=3 rash, blistering, or severe hypersensitivity to prior treatment with immunomodulatory drugs such as th
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 and American Society of Transplantation and Cellular Therapy (ASTCT) Consensus Grading for Cytokine Release Syndrome up to approximately 3 years
- Secondary Outcome Measures
Name Time Method