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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03275103




Registration number
NCT03275103
Ethics application status
Date submitted
5/09/2017
Date registered
7/09/2017

Titles & IDs
Public title
Dose-Escalation Study of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)
Scientific title
An Open-Label, Multicenter, Phase I Trial Evaluating the Safety and Pharmacokinetics of Escalating Doses of Cevostamab (BFCR4350A) in Patients With Relapsed or Refractory Multiple Myeloma
Secondary ID [1] 0 0
2018-001041-13
Secondary ID [2] 0 0
GO39775
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

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

Experimental: Arm A: Single Step Dose Escalation for Cevostamab - Study drug will be administered intravenously on a 21-day cycle. The step-up dose will be given on Cycle 1 Day 1 and the target dose will be given on C1D8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.

Experimental: Arm B: Double Step Dose Escalation for Cevostamab - In Cycle 1, participants will receive 2 step-up doses and a target dose. The step-up dose will be given on Cycle 1 Day 1 and C1D8. The target dose will be given on C1D15. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.

Experimental: Arm C: Single Step Dose Expansion for Cevostamab - The single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A.

Experimental: Arm D: Double Step Dose Expansion for Cevostamab - The double step dose expansion stage of the study may use the dosing and assessment schedule from the double step dose escalation arm in Cycle 1, based on data from Arm B.

Experimental: Arm E: Expansion Phase for Tocilizumab Pretreatment - All participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of cevostamab and Cycle 1 cevostamab doses for other treatment arms.

Experimental: Arm F: Single Step Dose Expansion for Cevostamab - The single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A.

Experimental: Arm G: Double Step Dose Expansion for Cevostamab - The double step dose expansion stage of the study may use the dosing and assessment schedule from the double step dose escalation arm in Cycle 1, based on data from Arm B.

Experimental: Arm H: Triple Step Dose Escalation for Cevostamab - In Cycle 1, participants will receive 3 step-up doses and a target dose. The doses will be given on Cycle 1 Days 1, 2-4, 8, and 9-11. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.

Experimental: Arm I: Triple Step Dose Expansion for Cevostamab - The triple step dose expansion stage of the study may use the dosing and assessment schedule from the triple step dose escalation arm in Cycle 1, based on data from Arm H.

Experimental: Arm J: Expansion Phase for Tocilizumab Pretreatment - All participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of cevostamab and Cycle 1 cevostamab doses for other treatment arms.

Experimental: Arm K: Compressed Double Step Dose Expansion for Cevostamab - In Cycle 1, participants will receive 2 step-up doses and a target dose. The doses will be given on Cycle 1 Days 1, 4, and 8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.


Treatment: Drugs: Cevostamab
Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.

Treatment: Drugs: Tocilizumab
Tocilizumab will be administered as premedication during Cycle 1.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [1] 0 0
Up to approximately 8 years
Primary outcome [2] 0 0
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Timepoint [2] 0 0
Up to approximately 8 years
Primary outcome [3] 0 0
Arms E and J Only: Incidence and Severity of Cytokine-release Syndrome (CRS) Following Tocilizumab Premedication Followed by Treatment with Cevostamab
Timepoint [3] 0 0
Up to approximately 8 years
Secondary outcome [1] 0 0
Area Under the Concentration-Time Curve (AUC) of Cevostamab
Timepoint [1] 0 0
Up to approximately 8 years
Secondary outcome [2] 0 0
AUC of Tocilizumab
Timepoint [2] 0 0
Up to approximately 8 years
Secondary outcome [3] 0 0
Maximum Observed Serum Concentration (Cmax) of Cevostamab
Timepoint [3] 0 0
Up to approximately 8 years
Secondary outcome [4] 0 0
Cmax of Tocilizumab
Timepoint [4] 0 0
Up to approximately 8 years
Secondary outcome [5] 0 0
Minimum Observed Serum Concentration (Cmin) of Cevostamab
Timepoint [5] 0 0
Up to approximately 8 years
Secondary outcome [6] 0 0
Cmin of Tocilizumab
Timepoint [6] 0 0
Up to approximately 8 years
Secondary outcome [7] 0 0
Clearance (CL) of Cevostamab
Timepoint [7] 0 0
Up to approximately 8 years
Secondary outcome [8] 0 0
CL of Tocilizumab
Timepoint [8] 0 0
Up to approximately 8 years
Secondary outcome [9] 0 0
Volume of Distribution at Steady State (Vdss) of Cevostamab
Timepoint [9] 0 0
Up to approximately 8 years
Secondary outcome [10] 0 0
Vdss of Tocilizumab
Timepoint [10] 0 0
Up to approximately 8 years
Secondary outcome [11] 0 0
Serum Concentration of Cevostamab
Timepoint [11] 0 0
Up to approximately 8 years
Secondary outcome [12] 0 0
Serum Concentration of Tocilizumab
Timepoint [12] 0 0
Up to approximately 8 years
Secondary outcome [13] 0 0
Objective Response Rate (ORR)
Timepoint [13] 0 0
Up to approximately 8 years
Secondary outcome [14] 0 0
Duration of Response
Timepoint [14] 0 0
Up to approximately 8 years
Secondary outcome [15] 0 0
Change from Baseline in the Presence Anti-Drug Antibodies (ADAs)
Timepoint [15] 0 0
Up to approximately 8 years

Eligibility
Key inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Life expectancy of at least 12 weeks
* Participants must have relapsed or refractory (R/R) multiple myeloma (MM) for which no established therapy for MM is appropriate and available or be intolerant to those established therapies
* Adverse events from prior anti-cancer therapy resolved to Grade < or = 1, except any grade alopecia and/or peripheral sensory or motor neuropathy which must have resolved to Grade < or = 2
* Measurable disease defined by laboratory test results
* Female participants of childbearing age must agree to remain abstinent or use reliable contraceptive methods during the treatment period, and at least 5 months after last dose of study drug. Women must refrain from breastfeeding during the same period.
* Male participants must agree to refrain from donating sperm, to abstain or use a condom during the treatment period, and for at least 2 months after the last dose of tocilizumab (if applicable).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Inability to comply with protocol-mandated hospitalization and activities restrictions
* Pregnant or breastfeeding, or planning to become pregnant during the study or within 5 months after the last dose of cevostamab or within 3 months after the last dose of of tocilizumab (if applicable)
* Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate as anti-cancer therapy within 4 weeks before first infusion
* Prior treatment with systemic immunotherapeutic agents within 12 weeks or 5 half-lives of the drug, whichever is shorter, before first infusion
* Prior treatment with chimeric antigen receptor (CAR) T-cell therapy within 12 weeks before first cevostamab infusion
* Known treatment-related, immune-mediated adverse events associated with prior immunotherapeutic agents
* Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first cevostamab infusion
* Autologous stem cell transplantation (SCT) within 100 days prior to first infusion
* Prior allogeneic SCT or solid organ transplantation
* Absolute plasma cell count exceeding 500/micro L or 5% of the peripheral blood white cells
* History of autoimmune disease or of confirmed progressive multifocal leukoencephalopathy
* 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)
* Patients with known history of amyloidosis (e.g., positive Congo Red stain or equivalent in tissue biopsy)
* Patients with lesions in proximity of vital organs that may develop sudden decompensation/deterioration in the setting of a tumor flare
* History of other malignancy that could affect compliance with the protocol or interpretation of results
* Current or past history of central nervous system (CNS) disease, or CNS involvement by MM
* Significant cardiovascular disease that may limit a patient's ability to adequately respond to a CRS event
* Symptomatic active pulmonary disease requiring supplemental oxygen
* Within 14 days prior to first cevostamab infusion: 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 antibiotics within 4 weeks prior to first infusion
* Positive and quantifiable Epstein-Barr virus (EBV) polymerase chain reaction (PCR) or cytomegalovirus (CMV) PCR prior to first study treatment
* Known or suspected chronic active EBV infection, acute or chronic hepatitis C virus (HCV) infection
* Positive serologic or PCR test results for acute or chronic hepatitis B virus (HBV) infection
* Recent major surgery within 4 weeks prior to first infusion
* Human Immunodeficiency Virus (HIV) positive
* Any episode of active, symptomatic COVID-19 infection, or requiring treatment with IV antivirals for COVID-19 (not including COVID-19 primary prophylaxis) within 14 days, prior to first study treatment
* Administration of a live, attenuated vaccine within 4 weeks before first cevostamab infusion or anticipation that such a live attenuated vaccine will be required during the study
* Received systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), with the exception of corticosteroid treatment <=10 mg/day prednisone or equivalent within 2 weeks prior to first dose of cevostamab and, if applicable, tocilizumab premedication prior to first dose of cevostamab
* History of illicit drug or alcohol abuse within 12 months prior to screening
* Any medical condition or laboratory test abnormality that precludes the participant's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results

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
Single group
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
19/09/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
420
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Center - North Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment postcode(s) [2] 0 0
3051 - North Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Canada
State/province [10] 0 0
Alberta
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
Spain
State/province [13] 0 0
Navarra
Country [14] 0 0
Spain
State/province [14] 0 0
Salamanca

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Genentech, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Genentech, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: GO39775 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. only)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
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).


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03275103