Trial record 1 of 1 for:
NCT03467373
A Study of Glofitamab in Combination With Rituximab or Obinutuzumab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP), or Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (CHP) in Participants With Non-Hodgkin Lymphomas or With DLBCL
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| ClinicalTrials.gov Identifier: NCT03467373 |
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Recruitment Status :
Active, not recruiting
First Posted : March 16, 2018
Last Update Posted : March 2, 2023
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Sponsor:
Hoffmann-La Roche
Information provided by (Responsible Party):
Hoffmann-La Roche
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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 G/R CHOP or Pola-R-CHP in participants with 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 untreated DLBCL (>18 years of age with an age-adjusted International Prognostic Index (IPI) of 2-5). Glofitamab will be studied in combination with R-CHOP and Pola-R-CHP.
| 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 Drug: Polatuzumab vedotin | Phase 1 |
| 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 Ib Study Evaluating Glofitamab (RO7082859) in Combination With Rituximab (R) or Obinutuzumab (G) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP), or Polatuzumab Vedotin (POLA) Plus Rituximab (R), Cyclophosphamide, Doxorubicin, and Prednisone (CHP) 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 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Cyclophosphamide
Prednisone
Doxorubicin
Rituximab
Obinutuzumab
Polatuzumab vedotin
| Arm | Intervention/treatment |
|---|---|
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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 |
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Experimental: Part 2: DLBCL G/R-CHOP
Participants with untreated DLBCL will receive G-CHOP or R-CHOP in Cycle 1, followed by G/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.
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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 |
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Experimental: Part 2: DLBCL Pola-R-CHP
Participants with untreated DLBCL will receive Pola-R-CHP + glofitamab on Day 1 of each 21-day cycle for a maximum of 6 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. The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I.
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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: 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 Drug: Polatuzumab vedotin Polatuzumab vedotin 1.8 mg/kg administered IV on Day 1 of each 21-day cycle |
Primary Outcome Measures :
- Part I: Percentage of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 29 months ]
- Part I and II: Percentage of Participants with Adverse Events [ Time Frame: Up to 29 months ]
Secondary Outcome Measures :
- 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 ]
- Parts I and II: Percentage of Participants with Overall Response (Partial Response [PR] or Complete Response [CR]) [ Time Frame: Up to 29 months ]
- Parts I and II: Duration of Response (DOR) [ Time Frame: Up to 29 months ]
- Duration of CR [ Time Frame: Up to 29 months ]
- Progression-Free Survival (PFS) [ Time Frame: Up to 29 months ]
- Overall Survival (OS) [ Time Frame: Up to 29 months ]
- Time to First Complete Response (TFCR) [ Time Frame: Up to 29 months ]
- Time to First Response (TFOR) [ Time Frame: Up to 29 months ]
- 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 ]
- Parts I and II: Time to Maximum Serum Concentration (tmax) of Glofitamab [ Time Frame: Cycle 1 Day 1 up to 29 months ]
- Parts I and II: Maximum Serum Concentration (Cmax) of Glofitamab [ Time Frame: Cycle 1 Day 1 up to 29 months ]
- Parts I and II: Minimum Serum Concentration (Cmin) of Glofitamab [ Time Frame: Cycle 1 Day 1 up to 29 months ]
- Change from Baseline in T-cell Activation Markers [ Time Frame: Up to 29 months ]
Information from the National Library of Medicine
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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 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 final 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 </= 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 or Pola-R-CHP infusion on Cycle 1/Day 1
- Current Grade > 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease (only for participants treated in the polatuzumab vedotin arm)
- 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 immunochemotherapy
- 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 or extensive 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
Locations
Show 24 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
| 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: | March 2, 2023 |
| Last Verified: | March 2023 |
| 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 |