Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT04246086
Previous Study | Return to List | Next Study

A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab + Lenalidomide (+Len) or Glofitamab + Len With or Without Obinutuzumab; and Evaluating the Safety, Tolerability, and Pharmacokinetics of SC Versus IV Mosunetuzumab + Len in Participants With R/R Follicular Lymphoma

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: NCT04246086
Recruitment Status : Recruiting
First Posted : January 29, 2020
Last Update Posted : June 30, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of mosunetuzumab + lenalidomide, glofitamab + lenalidomide, and glofitamab + lenalidomide + obinutuzumab in participants with relapsed or refractory (R/R) follicular lymphoma (FL). This study will also compare the pharmacokinetics, pharmacodynamics, safety, efficacy, and immunogenicity of IV mosunetuzumab + len vs subcutaneous (SC) mosunetuzumab + len.

Condition or disease Intervention/treatment Phase
Follicular Lymphoma Drug: Glofitamab Drug: Mosunetuzumab (IV) Drug: Obinutuzumab Drug: Tocilizumab Drug: Lenalidomide Drug: Mosunetuzumab (SC) Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II, Open-Label, Multicenter Study With a Non-Randomized Stage Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab Plus Lenalidomide (+Len) or Glofitamab + Len With or Without Obinutuzumab, and a Randomized Stage Evaluating the Safety, Tolerability, and Pharmacokinetics of SC Versus IV Mosunetuzumab + Len in Patients With Relapsed or Refractory Follicular Lymphoma
Actual Study Start Date : August 12, 2020
Estimated Primary Completion Date : March 29, 2024
Estimated Study Completion Date : March 31, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Mosunetuzumab + Lenalidomide (Non-randomized)
Participants will receive treatment with mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)
Drug: Mosunetuzumab (IV)
Participants will receive IV mosunetuzumab as defined by the study protocol
Other Name: RO7030816

Drug: Tocilizumab
Participants will receive IV tocilizumab as needed for adverse reactions as defined by the study protocol
Other Name: RO4877533

Drug: Lenalidomide
Participants will receive oral lenalidomide as defined by the study protocol

Experimental: Glofitamab + Lenalidomide (Non-randomized)
Participants will receive obinutuzumab pretreatment, followed by treatment with glofitamab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)
Drug: Glofitamab
Participants will receive intravenous (IV) CD20-TCB as defined by the study protocol
Other Name: RO7082859, CD20-TCB

Drug: Obinutuzumab
Participants will receive IV obinutuzumab as defined by the study protocol
Other Name: RO5072759

Drug: Tocilizumab
Participants will receive IV tocilizumab as needed for adverse reactions as defined by the study protocol
Other Name: RO4877533

Drug: Lenalidomide
Participants will receive oral lenalidomide as defined by the study protocol

Experimental: Glofitamab + Obinutuzumab + Lenalidomide (Non-randomized)
Participants will receive obinutuzumab pretreatment, followed by treatment with glofitamab plus lenalidomide and obinutuzumab for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)
Drug: Glofitamab
Participants will receive intravenous (IV) CD20-TCB as defined by the study protocol
Other Name: RO7082859, CD20-TCB

Drug: Obinutuzumab
Participants will receive IV obinutuzumab as defined by the study protocol
Other Name: RO5072759

Drug: Tocilizumab
Participants will receive IV tocilizumab as needed for adverse reactions as defined by the study protocol
Other Name: RO4877533

Drug: Lenalidomide
Participants will receive oral lenalidomide as defined by the study protocol

Experimental: Arm A: IV Mosunetuzumab + Len (Randomized)
Participants will receive treatment with IV mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)
Drug: Mosunetuzumab (IV)
Participants will receive IV mosunetuzumab as defined by the study protocol
Other Name: RO7030816

Drug: Lenalidomide
Participants will receive oral lenalidomide as defined by the study protocol

Experimental: Arm B: SC Mosunetuzumab + Len (Randomized)
Participants will receive treatment with SC mosunetuzumab plus lenalidomide for 12 cycles total (cycle length = 21 days for Cycle 1, 28 days from Cycle 2 onward)
Drug: Lenalidomide
Participants will receive oral lenalidomide as defined by the study protocol

Drug: Mosunetuzumab (SC)
Participants will receive SC mosunetuzumab as defined by the study protocol
Other Name: RO7030816




Primary Outcome Measures :
  1. Dose-Limiting Toxicities (DLTs) [ Time Frame: Cycle 2 Days 1-28 (cycle length = 28 days) ]
  2. Percentage of Participants with Adverse Events [ Time Frame: From baseline to 90 days after the last dose of study drug ]
  3. Cumulative Area under the Curve over Cycles 1-3 (AUC1-3) of Mosunetuzumab [ Time Frame: Day 1 - Day 78 ]
  4. Serum Trough Concentration at Steady State Approximated by Cycle 4 (Ctrough, c4) of Mosunetuzumab [ Time Frame: Day 106 ]

Secondary Outcome Measures :
  1. Complete Response Rate (CRR) [ Time Frame: Up to the end of Cycle 12 (cycle length = 28 days) ]
  2. Objective Response Rate (ORR) [ Time Frame: Up to the end of Cycle 12 (cycle length = 28 days) ]
  3. Duration of Response (DOR) [ Time Frame: From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, up to the end of Cycle 8 (cycle length = 28 days) ]
  4. Duration of Complete Reponse (DOCR) [ Time Frame: From the first occurrence of a documented complete response (CR) to disease progression, relapse, or death from any cause, whichever occurs first, up to the end of Cycle 12 (cycle length = 28 days) ]
  5. Minimum Serum Concentration (Cmin) of Mosunetuzumab [ Time Frame: At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment) ]
  6. Maximum Serum Concentration (Cmax) of Mosunetuzumab [ Time Frame: At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment) ]
  7. Area Under the Concentration vs Time Curve (AUC) of Mosunetuzumab [ Time Frame: At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment) ]
  8. Cmin of Glofitamab [ Time Frame: At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment) ]
  9. Cmax of Glofitamab [ Time Frame: At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment) ]
  10. AUC of Glofitamab [ Time Frame: At pre-defined intervals from Cycle 1 Day 1 through follow up (2 years after last treatment) ]
  11. Percentage of Participants with Anti-Drug Antibodies (ADAs) to Glofitamab [ Time Frame: At pre-defined intervals from baseline through follow-up (2 years after last treatment) ]
  12. Percentage of Participants with ADAs to Mosunetuzumab [ Time Frame: At pre-defined intervals from baseline through follow-up (2 years after last treatment) ]
  13. Percentage of Participants with AEs (Arms A and B) [ Time Frame: From baseline to 90 days after the last dose of study drug ]
  14. Cumulative AUC Over Cycles 1-2 (AUCc1-2) of Mosunetuzumab (Arms A and B) [ Time Frame: Day 1 - Day 50 ]
  15. Serum Trough Concentration in Cycle 2 (Ctrough, c2) of Mosunetuzumab (Arms A and B) [ Time Frame: Day 50 ]
  16. AUC at Steady State (AUCss) (Arms A and B) [ Time Frame: Cycle 4 (cycle length = 28 days) ]


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, 1, or 2
  • R/R FL after treatment with at least one prior chemo immunotherapy regimen that included an anti CD20 monoclonal antibody (MAb)
  • Histologically documented FL of Grade 1, 2, or 3a, and that expresses CD20 at time of diagnosis as determined by the local laboratory
  • Fluorodeoxyglucose avid lymphoma (i.e., positron emission tomography (PET) positive lymphoma)
  • At least one bi dimensionally measurable nodal lesion (>1.5 cm in its largest dimension by PET- computed tomography (CT) scan), or at least one bi dimensionally measurable extranodal lesion (>1.0 cm in its largest dimension by PET-CT scan)
  • Availability of a representative tumor specimen and the corresponding pathology report for confirmation of the diagnosis of FL
  • Adequate hematologic function (unless due to underlying lymphoma, per the investigator) as defined by the protocol
  • Normal laboratory values (unless due to underlying lymphoma) as defined by the protocol
  • Agreement to comply with all local requirements of the Len risk minimization plan
  • For women of childbearing potential: agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of < 1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period, and for at least 12 months after the final dose of glofitamab, 28 days after the last dose of Len, 18 months after the last dose of G, 3 months after the final dose of tocilizumab, and 3 months after the final dose of Mosun. Women must refrain from donating eggs during this same period
  • For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm, with female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 2 months after the final dose of glofitamab, 28 days after last dose of Len, 18 months after the last dose of G, 3 months after the final dose of tocilizumab, and 3 months after the final dose of Mosun

Exclusion Criteria

  • Grade 3b FL
  • History of transformation of indolent disease to diffuse large B-cell lymphoma (DLBCL)
  • Documented refractoriness to an obinutuzumab monotherapy containing regimen in glofitamab-containing treatment combination
  • Active or history of central nervous system (CNS) lymphoma or leptomeningeal infiltration
  • Documented refractoriness to lenalidomide, defined as no response (partial response (PR) or complete response (CR)) within 6 months of therapy
  • Prior standard or investigational anti-cancer therapy as specified by the protocol
  • Clinically significant toxicity (other than alopecia) from prior treatment that has not resolved to Grade <=2 prior to Day 1 of Cycle 1
  • Known history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis or evidence of active pneumonitis on screening chest CT scan
  • Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1
  • History of solid organ transplantation
  • History of severe allergic or anaphylactic reaction to humanized, chimeric or murine MAbs
  • Known sensitivity or allergy to murine products
  • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the glofitamab, Mosun, G, Len, or thalidomide formulation, including mannitol
  • History of erythema multiforme, Grade >=3 rash, or blistering following prior treatment with immunomodulatory derivatives
  • Known history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis or evidence of active pneumonitis on screening chest CT scan
  • Known active bacterial, viral, fungal, or other infection, or any major episode of infection requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1
  • Known or suspected chronic active Epstein-Barr virus infection or hemophagocytic syndrome
  • Known history of macrophage activating syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH)
  • Active Hepatitis B and Hepatitis C infection or autoimmune disease requiring treatment
  • Prior allogenic hematopoietic stem cell transplant
  • Known history of HIV positive status
  • History of progressive multifocal leukoencephalopathy
  • Administration of a live, attenuated vaccine within 4 weeks before first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study
  • Other malignancy that could affect compliance with the protocol or interpretation of results
  • Prior allogenic hematopoietic stem cell transplant (HSCT)
  • Contraindication to treatment for thromboembolism prophylaxis
  • Grade >=2 neuropathy
  • Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including, but not limited to significant cardiovascular disease or significant pulmonary disease
  • Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1 Day 1 or anticipation of a major surgical procedure during the course of the study
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Inadequate hematologic function
  • Any of the following abnormal laboratory values
  • Pregnant or lactating or intending to become pregnant during the study
  • Life expectancy < 3 months
  • Unable to comply with the study protocol, in the investigator's judgment
  • History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
  • Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's or Medical Monitor's judgment, precludes the patient's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results

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): NCT04246086


Contacts
Layout table for location contacts
Contact: Reference Study ID Number: CO41942 https://forpatients.roche.com/ 888-662-6728 global-roche-genentech-trials@gene.com

Locations
Show Show 19 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04246086    
Other Study ID Numbers: CO41942
2019-004291-20 ( EudraCT Number )
First Posted: January 29, 2020    Key Record Dates
Last Update Posted: June 30, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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
Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Lenalidomide
Obinutuzumab
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Immunological