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Trial record 1 of 1 for:    NCT03467373
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A Study of Glofitamab in Combination With Rituximab or Obinutuzumab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Participants With Non-Hodgkin Lymphomas and Participants With DLBCL

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ClinicalTrials.gov Identifier: NCT03467373
Recruitment Status : Recruiting
First Posted : March 16, 2018
Last Update Posted : July 17, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:

This is a phase 1B, multi-center, dose-finding study of glofitamab administered in combination with obinutuzumab (Gazyva; [G]), rituximab (R) and standard doses of CHOP (G/R-CHOP or R-CHOP) in participants with r/r NHL and untreated diffuse large B-cell lymphoma (DLBCL). Evaluating the safety, preliminary activity, pharmacokinetic (PK), and pharmacodynamic effects of this combination will be the main objectives of this study. The study is divided in two parts:

  • Part I: Dose finding in participants with r/r NHL; test use of G vs R in Cycle 1
  • Part II: Dose Expansion. The maximum tolerated dose or optimal biological dose (MTD or OBD) will be further assessed in participants with r/r NHL and those with untreated DLBCL (>60 years of age with an age-adjusted International Prognostic Index (IPI) of 2-3). Particularly, the impact of using glofitamab plus G/R-CHOP (i.e., add-on arm) versus glofitamab plus CHOP (i.e., replacement arm) will be assessed in untreated DLBCL participants.

Condition or disease Intervention/treatment Phase
B-Cell Lymphoma Non-Hodgkin Lymphoma Drug: Glofitamab Drug: Obinutuzumab (G) Drug: Rituximab (R) Drug: Tocilizumab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 172 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1B Study Evaluating Glofitamab in Combination With Rituximab (R) or Obinutuzumab (G) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Participants With Relapsed or Refractory Non-Hodgkin Lymphoma (R/R NHL) or in Participants With Untreated Diffuse Large B-Cell Lymphoma (DLBCL)
Actual Study Start Date : March 13, 2018
Estimated Primary Completion Date : December 16, 2023
Estimated Study Completion Date : December 16, 2023


Arm Intervention/treatment
Experimental: Part 1: Dose Escalation r/r NHL

Dose finding in participants with r/r NHL: the study will explore different doses of glofitamab in the induction period, starting at a dose of 70 mcg administered in combination with standard of care doses of G/R CHOP and R-CHOP every 3 weeks (Q3W). Participants with r/r NHL will receive 6 cycles of induction treatment (G/R-CHOP). Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6. Participants who achieve a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOInd) may optionally receive post-induction treatment (referred to as maintenance) with glofitamab alone.

The use of G versus R in Cycle 1 will be compared in parallel dose escalation cohorts.

Drug: Glofitamab
Glofitamab will be administered intravenously (IV) as a step-up dose for Cycle 2 on Days 8 and 15, and as a single dose from Cycle 3 onwards.
Other Name: RO7082859

Drug: Obinutuzumab (G)
Obinutuzumab 1000 mg single dose IV infusion on Day 1 of Cycle 1 only
Other Name: Gazyva

Drug: Rituximab (R)
Rituximab will be administered as an IV infusion at a dose of 375 mg/m^2 on Day 1 of each 21-day cycle starting from Cycle 1 to Cycle 6 (Part 1) or from Cycles 1-6 (up to 8) (Part 2: DLBCL R-CHOP).
Other Name: Rituxan

Drug: Tocilizumab
Tocilizumab will be administered as an IV infusion as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. Tocilizumab will be given as rescue medication.
Other Name: Actemra

Drug: Cyclophosphamide
Cyclophosphamide 750 mg/m^2 administered IV on Day 1 of each 21-day cycle

Drug: Doxorubicin
Doxorubicin 50 mg/m^2 administered IV on Day 1 of each 21-day cycle

Drug: Vincristine
Vincristine 1.4 mg/m^2 administered by IV push on Day 1 of each 21-day cycle with a recommended cap of 2 mg
Other Name: Oncovin

Drug: Prednisone
Prednisone 100 mg/day orally on Days 1-5 (prednisone on Day 1 may be administered IV, with the remaining doses on Days 2-5 to be administered orally) of each 21-day cycle

Experimental: Part 2: Dose Expansion r/r NHL
Participants with r/r NHL will be assigned to an expansion cohort to further explore glofitamab at the MTD/OBD determined in Part I.
Drug: Glofitamab
Glofitamab will be administered intravenously (IV) as a step-up dose for Cycle 2 on Days 8 and 15, and as a single dose from Cycle 3 onwards.
Other Name: RO7082859

Drug: Obinutuzumab (G)
Obinutuzumab 1000 mg single dose IV infusion on Day 1 of Cycle 1 only
Other Name: Gazyva

Drug: Rituximab (R)
Rituximab will be administered as an IV infusion at a dose of 375 mg/m^2 on Day 1 of each 21-day cycle starting from Cycle 1 to Cycle 6 (Part 1) or from Cycles 1-6 (up to 8) (Part 2: DLBCL R-CHOP).
Other Name: Rituxan

Drug: Tocilizumab
Tocilizumab will be administered as an IV infusion as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. Tocilizumab will be given as rescue medication.
Other Name: Actemra

Drug: Cyclophosphamide
Cyclophosphamide 750 mg/m^2 administered IV on Day 1 of each 21-day cycle

Drug: Doxorubicin
Doxorubicin 50 mg/m^2 administered IV on Day 1 of each 21-day cycle

Drug: Vincristine
Vincristine 1.4 mg/m^2 administered by IV push on Day 1 of each 21-day cycle with a recommended cap of 2 mg
Other Name: Oncovin

Drug: Prednisone
Prednisone 100 mg/day orally on Days 1-5 (prednisone on Day 1 may be administered IV, with the remaining doses on Days 2-5 to be administered orally) of each 21-day cycle

Experimental: Part 2: DLBCL G/R-CHOP
Participants with untreated DLBCL will receive G-CHOP or R-CHOP in Cycle 1, followed by R-CHOP + glofitamab for subsequent cycles. Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6 (up to 8). The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I.
Drug: Glofitamab
Glofitamab will be administered intravenously (IV) as a step-up dose for Cycle 2 on Days 8 and 15, and as a single dose from Cycle 3 onwards.
Other Name: RO7082859

Drug: Obinutuzumab (G)
Obinutuzumab 1000 mg single dose IV infusion on Day 1 of Cycle 1 only
Other Name: Gazyva

Drug: Rituximab (R)
Rituximab will be administered as an IV infusion at a dose of 375 mg/m^2 on Day 1 of each 21-day cycle starting from Cycle 1 to Cycle 6 (Part 1) or from Cycles 1-6 (up to 8) (Part 2: DLBCL R-CHOP).
Other Name: Rituxan

Drug: Tocilizumab
Tocilizumab will be administered as an IV infusion as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. Tocilizumab will be given as rescue medication.
Other Name: Actemra

Drug: Cyclophosphamide
Cyclophosphamide 750 mg/m^2 administered IV on Day 1 of each 21-day cycle

Drug: Doxorubicin
Doxorubicin 50 mg/m^2 administered IV on Day 1 of each 21-day cycle

Drug: Vincristine
Vincristine 1.4 mg/m^2 administered by IV push on Day 1 of each 21-day cycle with a recommended cap of 2 mg
Other Name: Oncovin

Drug: Prednisone
Prednisone 100 mg/day orally on Days 1-5 (prednisone on Day 1 may be administered IV, with the remaining doses on Days 2-5 to be administered orally) of each 21-day cycle

Experimental: Part 2: DLBCL CHOP
Participants with untreated DLBCL will receive G-CHOP or R-CHOP in Cycle 1, followed by CHOP + glofitamab for subsequent cycles. Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6 (up to 8). The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I.
Drug: Glofitamab
Glofitamab will be administered intravenously (IV) as a step-up dose for Cycle 2 on Days 8 and 15, and as a single dose from Cycle 3 onwards.
Other Name: RO7082859

Drug: Rituximab (R)
Rituximab will be administered as an IV infusion at a dose of 375 mg/m^2 on Day 1 of each 21-day cycle starting from Cycle 1 to Cycle 6 (Part 1) or from Cycles 1-6 (up to 8) (Part 2: DLBCL R-CHOP).
Other Name: Rituxan

Drug: Tocilizumab
Tocilizumab will be administered as an IV infusion as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. Tocilizumab will be given as rescue medication.
Other Name: Actemra

Drug: Cyclophosphamide
Cyclophosphamide 750 mg/m^2 administered IV on Day 1 of each 21-day cycle

Drug: Doxorubicin
Doxorubicin 50 mg/m^2 administered IV on Day 1 of each 21-day cycle

Drug: Vincristine
Vincristine 1.4 mg/m^2 administered by IV push on Day 1 of each 21-day cycle with a recommended cap of 2 mg
Other Name: Oncovin

Drug: Prednisone
Prednisone 100 mg/day orally on Days 1-5 (prednisone on Day 1 may be administered IV, with the remaining doses on Days 2-5 to be administered orally) of each 21-day cycle




Primary Outcome Measures :
  1. Part I: Percentage of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 29 months ]
  2. Part I and II: Percentage of Participants with Adverse Events [ Time Frame: Up to 29 months ]

Secondary Outcome Measures :
  1. Parts I and II: Percentage of Participants with a Complete Response (CR) as Assessed by the Investigator using Modified Lugano 2014 Criteria [ Time Frame: Up to 29 months ]
  2. Parts I and II: Percentage of Participants with Overall Response (Partial Response [PR] or Complete Response [CR]) [ Time Frame: Up to 29 months ]
  3. Parts I and II: Duration of Response (DOR) [ Time Frame: Up to 29 months ]
  4. Progression-Free Survival (PFS) [ Time Frame: Up to 29 months ]
  5. Overall Survival (OS) [ Time Frame: Up to 29 months ]
  6. Time to First Complete Response (TFCR) [ Time Frame: Up to 29 months ]
  7. Time to First Response (TFOR) [ Time Frame: Up to 29 months ]
  8. Parts I and II: Area Under the Serum Concentration Versus Time Curve (AUC) of Glofitamab [ Time Frame: Cycle 1 Day 1 up to 29 months ]
  9. Parts I and II: Time to Maximum Serum Concentration (tmax) of Glofitamab [ Time Frame: Cycle 1 Day 1 up to 29 months ]
  10. Parts I and II: Maximum Serum Concentration (Cmax) of Glofitamab [ Time Frame: Cycle 1 Day 1 up to 29 months ]
  11. Parts I and II: Minimum Serum Concentration (Cmin) of Glofitamab [ Time Frame: Cycle 1 Day 1 up to 29 months ]
  12. Change from Baseline in T-cell Activation Markers [ Time Frame: Up to 29 months ]


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.


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

Inclusion Criteria:

  • Age>/=18 years for participants with r/r NHL or > 60 years for participants with untreated DLBCL
  • For Part I r/r NHL dose-escalation, and Part II r/r NHL expansion: Histologically-confirmed NHL that is expected to express CD20, and which has relapsed/progressed following at least one prior treatment regimen containing R or G. Participants must be appropriate for treatment with CHOP and typically should not have been exposed to prior anthracyclines or must not exceed the cumulative lifetime dose of anthracyclines
  • For Part II untreated DLBCL expansion: Histologically confirmed previously-untreated DLBCL that is expected to express CD20
  • Able to provide a pretreatment biopsy between the last dose of last prior therapy and initiation of study medication at Cycle 1/Day 1
  • Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as >1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as >1.0 cm in its longest dimension.
  • Participants must have at least one measurable target lesion (> or = 1.5 cm) in its largest dimension by computed tomography (CT) scan
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for participants with r/r NHL; ECOG performance status 0-3 for participants with untreated DLBCL
  • Life expectancy (in the opinion of the Investigator) of 18 weeks
  • Adverse events (AEs) from prior anti-cancer therapy must have resolved to Grade < or = 1
  • Adequate liver function
  • Adequate hematological function
  • Adequate renal function
  • Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection
  • Negative test results for hepatitis C virus (HCV) and human immunodeficiency virus (HIV)

Exclusion Criteria:

  • Inability to comply with protocol mandated hospitalization and restrictions
  • Participants with known active infection, or reactivation of a latent infection, whether bacterial, viral (including, but not limited to Epstein Barr virus (EBV), cytomegalovirus (CMV), HBV, HCV, and HIV), fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics, this pertains to completion of last course of antibiotic treatment) within 4 weeks of dosing
  • Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radioimmuno-conjugates, antibody-drug conjugates, immune/cytokines, and monoclonal antibodies (e.g., anti-CTLA4, anti-PD1, and anti-PDL1) within 4 weeks or five half-lives of the drug, whichever is shorter, before G- or R-CHOP infusion on Cycle 1/Day 1
  • History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents, as follows: Grade >/=3 AEs, with the exception of Grade 3 endocrinopathy managed with replacement therapy; Grade 1-2 AEs that did not resolve to baseline after treatment completion
  • Contraindication to any of the individual components of the chemotherapy
  • Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent within 4 weeks prior to study treatment at Cycle 1/Day 1 infusion
  • Prior solid organ transplantation
  • Prior allogeneic stem cell transplantation
  • Autologous stem cell transplantation within 100 days prior to Cycle 1/Day 1
  • Prior treatment with CAR T-cell therapy within 30 days prior to study treatment at Cycle 1 Day 1
  • History of autoimmune disease
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
  • A history of confirmed progressive multifocal leukoencephalopathy
  • Current or past history of central nervous system (CNS) lymphoma
  • Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent. Participants who received corticosteroid treatment with </=30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to Cycle 1/Day 1. Participants may have received a brief (<7 days) course of systemic steroids (</=100 mg prednisone equivalent per day) prior to initiation of study therapy for control of lymphoma-related symptoms
  • Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders (bronchospasm, obstructive pulmonary disease), and known autoimmune diseases
  • Major surgery or significant traumatic injury < 28 days prior to the study treatment infusion at Cycle 1/Day 1 (excluding biopsies) or anticipation of the need for major surgery during study treatment
  • Participants with another invasive malignancy that could affect compliance with the protocol or interpretation of results
  • Significant cardiovascular disease
  • Left ventricular ejection fraction < 50%
  • Administration of a live, attenuated vaccine within 4 weeks before study treatment infusion on Cycle 1 Day 1 or anticipation that such a live, attenuated vaccine will be required during the study
  • History of illicit drug or alcohol abuse within 12 months prior to screening, in the Investigator's judgment
  • Any other diseases, metabolic dysfunction, physical examination finding (including mental status), or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
  • Participants with latent or active tuberculosis

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): NCT03467373


Contacts
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Contact: Reference Study ID: NP40126 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. only) global-roche-genentech-trials@gene.com

Locations
Show Show 23 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03467373    
Other Study ID Numbers: NP40126
2017-003648-18 ( EudraCT Number )
First Posted: March 16, 2018    Key Record Dates
Last Update Posted: July 17, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Prednisone
Cyclophosphamide
Rituximab
Doxorubicin
Vincristine
Obinutuzumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents