This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dose-Escalation Study of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)

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: NCT03275103
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : April 4, 2024
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
This is a phase I, multicenter, open-label, dose-escalation study of cevostamab administered as a single agent by IV infusion to participants with relapsed or refractory multiple myeloma (R/R MM).

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

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 420 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : September 19, 2017
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Tocilizumab

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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.
 Drug: Cevostamab
Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Other Name: BFCR4350A; RO7187797
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.
 Drug: Cevostamab
Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Other Name: BFCR4350A; RO7187797
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.
 Drug: Cevostamab
Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Other Name: BFCR4350A; RO7187797
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.
 Drug: Cevostamab
Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Other Name: BFCR4350A; RO7187797
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.
 Drug: Cevostamab
Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Other Name: BFCR4350A; RO7187797

Drug: Tocilizumab
Tocilizumab will be administered as premedication during Cycle 1.
Other Name: Actemra/RoActemra
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.
 Drug: Cevostamab
Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Other Name: BFCR4350A; RO7187797
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.
 Drug: Cevostamab
Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Other Name: BFCR4350A; RO7187797
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.
 Drug: Cevostamab
Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Other Name: BFCR4350A; RO7187797
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.
 Drug: Cevostamab
Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Other Name: BFCR4350A; RO7187797
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.
 Drug: Cevostamab
Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Other Name: BFCR4350A; RO7187797

Drug: Tocilizumab
Tocilizumab will be administered as premedication during Cycle 1.
Other Name: Actemra/RoActemra
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.
 Drug: Cevostamab
Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
Other Name: BFCR4350A; RO7187797


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to approximately 8 years ]
    An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.

  2. Percentage of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: Up to approximately 8 years ]
    Dose-Limiting Toxicities (DLTs) will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), except for Cytokine release syndrome (CRS), which will be graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) Consensus Grading for Cytokine Release Syndrome.

  3. Arms E and J Only: Incidence and Severity of Cytokine-release Syndrome (CRS) Following Tocilizumab Premedication Followed by Treatment with Cevostamab [ Time Frame: Up to approximately 8 years ]
    Cytokine release syndrome was recorded as an AE that generally occurs >30 minutes after the start of Cevostamab administration and at any time afterward in a given cycle.


Secondary Outcome Measures :
  1. Area Under the Concentration-Time Curve (AUC) of Cevostamab [ Time Frame: Up to approximately 8 years ]
    Defined as the total exposure of study drug.

  2. AUC of Tocilizumab [ Time Frame: Up to approximately 8 years ]
    Defined as the total exposure of study drug.

  3. Maximum Observed Serum Concentration (Cmax) of Cevostamab [ Time Frame: Up to approximately 8 years ]
    Defined as the maximum observed serum concentration of study drug.

  4. Cmax of Tocilizumab [ Time Frame: Up to approximately 8 years ]
    Defined as the maximum observed serum concentration of study drug.

  5. Minimum Observed Serum Concentration (Cmin) of Cevostamab [ Time Frame: Up to approximately 8 years ]
    Defined as the minimum observed serum concentration of study drug.

  6. Cmin of Tocilizumab [ Time Frame: Up to approximately 8 years ]
    Defined as the minimum observed serum concentration of study drug.

  7. Clearance (CL) of Cevostamab [ Time Frame: Up to approximately 8 years ]
    Defined as the volume of plasma cleared of the drug per unit time.

  8. CL of Tocilizumab [ Time Frame: Up to approximately 8 years ]
    Defined as the volume of plasma cleared of the drug per unit time.

  9. Volume of Distribution at Steady State (Vdss) of Cevostamab [ Time Frame: Up to approximately 8 years ]
    Defined as the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces.

  10. Vdss of Tocilizumab [ Time Frame: Up to approximately 8 years ]
    Defined as the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces.

  11. Serum Concentration of Cevostamab [ Time Frame: Up to approximately 8 years ]
  12. Serum Concentration of Tocilizumab [ Time Frame: Up to approximately 8 years ]
  13. Objective Response Rate (ORR) [ Time Frame: Up to approximately 8 years ]

    ORR is defined as percentage of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) .

    sCR is defined as CR (as defined below), plus: Normal FLC ratio and absence of clonal cells in bone marrow (BM) by immunohistochemistry (kappa/lambda ratio </=4:1 or >/=1:2 for kappa and lambda participants, respectively after counting >/=100 plasma cells).

    CR is defined as no evidence of initial monoclonal protein isotype(s) on immunofixation of the serum and urine, disappearance of any soft tissue plasmacytomas, and </= 5% plasma cells in BM.

    VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis; or >/=90% reduction in serum M-protein plus urine M-protein level <100 milligrams (mg)/24 hr.

    PR is defined as >/= 50% reduction of serum M-protein and reduction in 24-hour urine M-protein by >/= 90% or to < 200 mg/24 hours.


  14. Duration of Response [ Time Frame: Up to approximately 8 years ]
    Time from first occurrence of ORR (defined previously) to disease progression (PD) or death from any cause. PD: increase of >/=25% from lowest response value in one of the following: serum M-protein (absolute increase >/=0.5 grams per deciliter (g/dL); serum M-protein increase >/=1g/dL, if lowest M component was >/=5g/dL; urine M-protein (absolute increase >/=200 mg/24 hours); no measurable serum and urine M-protein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase >10 mg/dL); no measurable serum and urine M-protein levels and no measurable disease by FLC: BM plasma cell % irrespective of baseline status (absolute % >/=10%); new lesion(s) >/=50% increase from lowest point in sum of the products of diameters of > 1 lesion, or >/=50% increase in longest diameter of a previous lesion >1 centimeter (cm) in short axis; >/=50% increase in circulating plasma cells (minimum 200 cells per microliter) if only measure of disease.

  15. Change from Baseline in the Presence Anti-Drug Antibodies (ADAs) [ Time Frame: Up to approximately 8 years ]
    To evaluate the immune response to the study drug.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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:

  • 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).

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT03275103


Contacts
Layout table for location contacts
Contact: Reference Study ID Number: GO39775 https://forpatients.roche.com/ 888-662-6728 (U.S. only) global-roche-genentech-trials@gene.com

Locations
Show Show 18 study locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
Layout table for investigator information
Study Director: Clinical Trials Genentech, Inc.
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT03275103    
Other Study ID Numbers: GO39775
2018-001041-13 ( EudraCT Number )
2022-502053-34-00 ( Other Identifier: EU CT Number )
First Posted: September 7, 2017    Key Record Dates
Last Update Posted: April 4, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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