Celestimo: A Study Evaluating the Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide in Patients With Follicular Lymphoma After at Least One Line of Systemic Therapy

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04712097

Collaborator

(none)

400

Enrollment

111

Locations

Arms

90.1

Anticipated Duration (Months)

3.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of mosunetuzumab in combination with lenalidomide (M + Len) compared to rituximab in combination with lenalidomide (R + Len) in participants with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least one line of prior systemic therapy.

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Follicular Lymphoma	Drug: Mosunetuzumab Drug: Lenalidomide Drug: Rituximab Drug: Tociluzumab	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase III Randomized, Open-Label, Multicenter Study Evaluating Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide in Patients With Follicular Lymphoma After at Least One Line of Systemic Therapy

Actual Study Start Date :

Oct 27, 2021

Anticipated Primary Completion Date :

May 1, 2029

Anticipated Study Completion Date :

May 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: M + Len Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)	Drug: Mosunetuzumab Participants will receive intravenous (IV) mosunetuzumab in a step-up dosing schedule on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-12 Drug: Lenalidomide Participants will receive oral lenalidomide once daily on Days 1-21 of Cycles 2-12 (M + Len) or Cycles 1-12 (R + Len) Drug: Tociluzumab Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events
Experimental: R + Len Participants will receive weekly rituximab in Cycle 1, then on Day 1 of Cycles 3, 5, 6, 9, and 11. Participants will also receive lenalidomide in Cycles 1-12. (Cycle length = 28 days for Cycles 1-12)	Drug: Lenalidomide Participants will receive oral lenalidomide once daily on Days 1-21 of Cycles 2-12 (M + Len) or Cycles 1-12 (R + Len) Drug: Rituximab Participants will receive IV rituximab on Days 1, 8, 15, and 22 of Cycle 1, then on Day 1 of Cycles 3, 5, 7, 9, and 11 Drug: Tociluzumab Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events

Arm

Intervention/Treatment

Experimental: M + Len

Participants will receive mosunetuzumab for 12 cycles, plus lenalidomide from cycles 2-12 (Cycle length = 21 days for Cycle 1; cycle length = 28 days for Cycles 2-12)

Drug: Mosunetuzumab

Participants will receive intravenous (IV) mosunetuzumab in a step-up dosing schedule on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-12

Drug: Lenalidomide

Participants will receive oral lenalidomide once daily on Days 1-21 of Cycles 2-12 (M + Len) or Cycles 1-12 (R + Len)

Drug: Tociluzumab

Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events

Experimental: R + Len

Participants will receive weekly rituximab in Cycle 1, then on Day 1 of Cycles 3, 5, 6, 9, and 11. Participants will also receive lenalidomide in Cycles 1-12. (Cycle length = 28 days for Cycles 1-12)

Drug: Lenalidomide

Participants will receive oral lenalidomide once daily on Days 1-21 of Cycles 2-12 (M + Len) or Cycles 1-12 (R + Len)

Drug: Rituximab

Participants will receive IV rituximab on Days 1, 8, 15, and 22 of Cycle 1, then on Day 1 of Cycles 3, 5, 7, 9, and 11

Drug: Tociluzumab

Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) according to 2014 Lugano Response Criteria [From randomization to the first occurrence of disease progression as determined by an independent review committee (IRC) or death from any cause (up to approximately 8 years)]

Secondary Outcome Measures

PFS as Determined by the Investigator [From randomization to the first occurrence of disease progression or death from any cause (up to approximately 8 years)]
Complete Response Rate [Up to approximately 8 years]
Objective Response Rate (ORR) [Up to approximately 8 years]
Overall Survival (OS) [From randomization to death from any cause (up to approximately 8 years)]
Duration of Objective Response (DOR) [From the first occurrence of a documented objective response (complete response or partial response) to disease progression or death from any cause, whichever occurs first (up to approximately 8 years)]
Duration of Complete Reponse (CR) [From the first occurrence of a documented CR to disease progression or death from any cause, whichever occurs first (up to approximately 8 years)]
Time to Deterioration in Physical Functioning and Fatigue, as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) [Up to approximately 8 years]
Time to Deterioration in Lymphoma Symptoms, as Measured by the Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS) [Up to approximately 8 years]
Percentage of Participants with Adverse Events (AEs) [Up to approximately 8 years]
Serum Concentration of M + Len [Up to approximately 8 years]
Area Under the Curve (AUC) of M + Len [Up to approximately 8 years]
Percentage of Participants with Anti-Drug Antibodies (ADAs) [Up to approximately 8 years]
Time to Next Anti-Lymphoma Treatment (TTNALT) [From randomization to the first documented administration of a new anti-lymphoma treatment (up to approximately 8 years)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
Histologically documented CD20+ FL (Grades 1-3a)
Requiring systemic therapy assessed by investigator based on tumor size and/or Groupe d'Etude des Lymphomes Folliculaires criteria
Received at least one prior systemic lymphoma therapy, which included prior immunotherapy or chemoimmunotherapy
Availability of a representative tumor specimen and the corresponding pathology report at the time of relapse/persistence for confirmation of the diagnosis of FL. Pretreatment sample of at least 1 core-needle, excisional or incisional tumor biopsy is required. Cytological or fine-needle aspiration samples are not acceptable. Fresh pretreatment biopsy is preferred. Patients who are unable to undergo biopsy procedures may be eligible for study enrollment if an archival tumor tissue sample (preferably from the most recent relapse/persistence) as paraffin blocks or at least 15 unstained slides, or in accordance with local regulatory requirements, can be sent to the Sponsor.
Adequate hematologic function (unless due to underlying lymphoma, per the investigator)
Agreement to comply with all local requirements of the lenalidomide risk minimization plan, which includes the global pregnancy prevention program.
For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use 2 adequate methods of contraception, including at least 1 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 (including periods of treatment interruption), and for at least 28 days after the last dose of lenalidomide, 3 months after the final dose of tocilizumab (if applicable), mosunetuzumab, and 12 months after final dose of rituximab. Women must refrain from donating eggs during this same period.
For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined: 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 28 days after last dose of lenalidomide, 3 months after the final dose of tocilizumab (if applicable), mosunetuzumab and 12 months after the final dose of rituximab. Men must refrain from donating sperm during this same period.

Exclusion Criteria:

Grade 3b FL
History of transformation of indolent disease to diffuse-large B cell lymphoma
Documented refractoriness to lenalidomide, defined as no response (partial response or complete response) or relapse within 6 months of therapy
Active or history of CNS lymphoma or leptomeningeal infiltration
Prior standard or investigational anti-cancer therapy as specified: Lenalidomide exposure within 12 months prior to Day 1 of Cycle 1; Chimeric antigen receptor T cell therapy within 30 days prior to Day 1 of Cycle 1; Radioimmunoconjugate within 12 weeks prior to Day 1 of Cycle 1; Monoclonal antibody or antibody-drug conjugate within 4 weeks prior to Cycle 1 Day 1; Treatment with any anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first dose of study treatment
Clinically significant toxicity (other than alopecia) from prior treatment that has not resolved to Grade </= 1 (per National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0) prior to Day 1 of Cycle 1
Treatment with systemic immunosuppressive medications, including, but not limited to prednisone (> 20 mg), 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 monoclonal antibodies
Known sensitivity or allergy to murine products
Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary (CHO) cells or any component of the mosunetuzumab, rituximab, tocilizumab, lenalidomide, or thalidomide formulation, including mannitol
History of erythema multiforme, Grade >/= 3 rash, or blistering following prior treatment with immunomodulatory derivatives
History of interstitial lung disease, drug-induced pneumonitis, and autoimmune pneumonitis
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 (EBV) infection
Known or suspected history of hemophagocytic lymphohistiocytosis
Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis
Active Hepatitis B infection
Active Hepatitis C infection
Known history of HIV positive status
History of progressive multifocal leukoencephalopathy (PML)
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
Active autoimmune disease requiring treatment
History of autoimmune disease, including, but not limited to: myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
Prior allogeneic stem cell transplantation
Contraindication to treatment for thromboembolism prophylaxis
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 (e.g., New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm)
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
Pregnant or lactating or intending to become pregnant during the study
Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator'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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
2	cCare	Encinitas	California	United States	92024
3	Cancer & Hematology Center of West Michigan	Grand Rapids	Michigan	United States	49546
4	Washington University; Wash Uni. Sch. Of Med	Saint Louis	Missouri	United States	63110
5	Wake Forest Univ Health Svcs; Section on Hem and Onc	Winston-Salem	North Carolina	United States	27157
6	MD Anderson Cancer Center	Houston	Texas	United States	77030
7	Calvary Mater Newcastle	Waratah	New South Wales	Australia	2298
8	Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology	Woolloongabba	Queensland	Australia	4102
9	Royal Adelaide Hospital; Haematology Clinical Trials	Adelaide	South Australia	Australia	5000
10	Geelong Hospital; Andrew Love Cancer Centre	Geelong	Victoria	Australia	3220
11	ICTR Curitiba	Curitiba	PR	Brazil	80510-130
12	Hospital das Clinicas - UFRGS	Porto Alegre	RS	Brazil	90035-903
13	Hospital Mae de Deus	Porto Alegre	RS	Brazil	90470-340
14	Hospital Alemao Oswaldo Cruz	Sao Paulo	SP	Brazil	01323-903
15	Peking University First Hospital	Beijing City		China	100034
16	Beijing Cancer Hospital	Beijing		China	100142
17	Peking University Third Hospital	Beijing		China	100191
18	The First Hospital of Jilin University	Changchun City		China	130021
19	Cancer Center, Sun Yat-sen University of Medical Sciences; Department of Medical Oncology	Guangzhou City		China	510060
20	The 1st Affiliated Hospital of Nanchang Unversity	Nanchang		China	330019
21	Jiangsu Province Hospital	Nanjing		China	210036
22	Fudan University Shanghai Cancer Center; Medical Oncology	Shanghai City		China	201315
23	Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai		China	200092
24	Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences	Tianjin City		China	300020
25	Tianjin Cancer Hospital	Tianjin		China	300060
26	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City		China	430023
27	Tongji Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City		China	430030
28	The First Affiliated Hospital of Xiamen University	Xiamen		China	361003
29	Zhejiang Cancer Hospital	Zhejiang		China	310022
30	The First Affiliated Hospital of Zhengzhou University	Zhengzhou		China	450052
31	Centre Hospitalier de La Cote Basque; Hematologie	Bayonne		France	64109
32	Ch De Chambery; Hematologie Oncologie	Chambery		France	73011
33	Hopital Henri Mondor; Hematologie Clinique	Creteil		France	94010
34	Hopital Claude Huriez; Hematologie	Lille		France	59037
35	Institut Paoli Calmettes	Marseille		France	13009
36	CHU Saint Eloi; Service d'Hématologie Clinique	Montpellier		France	34295
37	CHU NANTES - Hôtel Dieu; Service d'Hematologie Clinique	Nantes		France	44093
38	Centre Antoine Lacassagne;B4 Hematologie Cancerologie	Nice		France	06189
39	CHU de Nîmes - Hôpital Carémeau	Nimes		France	30029
40	Hôpital Saint-Louis; Service d'Hématologie	Paris		France	75475
41	Hopital Saint Antoine; Hematologie Clinique	Paris		France	75571
42	Hopital De Haut Leveque; Hematologie Clinique	Pessac		France	33604
43	Ch Lyon Sud; Hemato Secteur Jules Courmont	Pierre Benite		France	69495
44	Hopital De La Miletrie; Hematologie Et Oncologie Medicale	Poitiers		France	86021
45	CHU de Reims	Reims		France	51100
46	CHU Pontchaillou	Rennes		France	35033
47	Centre Henri Becquerel; Service Hématologie	Rouen		France	76038
48	ICLN;Hopital De Jour Rdc	St Priest En Jarez		France	42271
49	ICANS	Strasbourg		France	67200
50	Vivantes Klinikum Am Urban Klinik für Innere Medizin Hämatologie und Onkologie	Berlin		Germany	10967
51	Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III, Hämatologie und Onkologie	Chemnitz		Germany	09113
52	BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie	Dresden		Germany	01307
53	Marien-Hospital Klinik f.Hämatologie Onkologie u.Palliativmedizin	Düsseldorf		Germany	40479
54	Universitätsklinikum Halle; Klinik für Innere Medizin IV; Hämatologie und Onkologie	Halle (Saale)		Germany	06120
55	Universitaetsklinikum des Saarlandes; medizinische Klinik und Poliklinik; Innere Medizin I	Homburg/Saar		Germany	64421
56	Westpfalz-Klinikum GmbH; Innere Medizin 1, Hämatologie und internistischen Onkologie	Kaiserslautern		Germany	67655
57	Klinik und Poliklinik f. Innere Medizin III des Universitätsklinikums Regensburg	Regensburg		Germany	93053
58	Universitätsklinik Rostock; Klinik für Innere Med. III, Abteilung Hämatologie/Onkologie	Rostock		Germany	18057
59	Universtitätsklinikum Ulm; Klinik für Innere Medizin III	Ulm		Germany	89081
60	A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna	Bologna	Emilia-Romagna	Italy	40138
61	U.O. Ematologia AUSL Ravenna	Ravenna	Emilia-Romagna	Italy	48121
62	Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora	Milano	Lombardia	Italy	20122
63	Ospedali Riuniti Umberto I; Clinica di Ematologia	Ancona	Marche	Italy	60100
64	Azienda Ospedaliera Universitaria Careggi	Florence	Toscana	Italy	50134
65	Ematologia/immunologia Clinica Azienda Ospedaliera Policlinico di Padova	Padova	Veneto	Italy	35128
66	Aichi Cancer Center	Aichi		Japan	464-8681
67	National Cancer Center Hospital East	Chiba		Japan	277-8577
68	Kumamoto University Hospital	Kumamoto		Japan	860-8556
69	University Hospital Kyoto Prefectural University of Medicine	Kyoto		Japan	602-8566
70	Mie University Hospital	Mie		Japan	514-8507
71	Tohoku University Hospital	Miyagi		Japan	980-8574
72	Okayama University Hospital	Okayama		Japan	700-8558
73	Osaka Metropolitan University Hospital	Osaka		Japan	545-8586
74	National Cancer Center Hospital	Tokyo		Japan	104-0045
75	The Cancer Institute Hospital of JFCR	Tokyo		Japan	135-8550
76	Pusan National University Hospital	Busan		Korea, Republic of	49241
77	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13605
78	Seoul National University Hospital	Seoul		Korea, Republic of	03080
79	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
80	Asan Medical Center	Seoul		Korea, Republic of	05505
81	Samsung Medical Center	Seoul		Korea, Republic of	06351
82	Seoul St Mary's Hospital	Seoul		Korea, Republic of	06591
83	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland
84	Szpitale Pomorskie Sp. z o. o.; Oddział Hematologii i Transplantologii Szpiku	Gdynia		Poland	81-519
85	Oddzial Kliniczny Hematologii SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn		Poland	10-228
86	Instytut Hematologii i Transfuzjologii; Klinika Hematologii	Warszawa		Poland	02-776
87	Uniwersytecki Szpital Kliniczny; Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku	Wrocław		Poland	50-367
88	City Clinical Botkin's Hospital; City Hematological Center	Moscow		Russian Federation	125284
89	Regional Clinical Hospital N.A. Semashko; Hematology	Nizhny Novgorod		Russian Federation	603126
90	Penza Regional Oncology Dispensary	Penza		Russian Federation	440071
91	Hospital de Donostia; Servicio de Oncologia	Guipuzcoa		Spain	20014
92	Hospital Universitario la Paz; Servicio de Hematologia	Madrid		Spain	28046
93	Hospital General Universitario J.M Morales Meseguer; Servicio de Hematología	Murcia		Spain	30008
94	Hospital Universitario Virgen del Rocio; Servicio de Hematologia	Sevilla		Spain	41013
95	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia		Spain	46010
96	Chang Gung Medical Foundation - Kaohsiung; Oncology; Division of Hematology-Oncology	Kaoisung		Taiwan	833
97	Taipei Veterans General Hospital	Taipei City		Taiwan	112
98	National Taiwan Universtiy Hospital; Division of Hematology	Taipei		Taiwan	100
99	Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology	Taoyuan		Taiwan	333
100	Gulhane Training and Research Hospital	Ankara		Turkey	06010
101	Hacettepe Uni Medical Faculty; Hematology	Ankara		Turkey	06100
102	Atakent Acibadem Private Hosptial Halkali Merkez Mh.,	Istanbul		Turkey	34303
103	Marmara Üniversitesi İstanbul Pendik Eğitim Ve Araştirma Hastanesi	Istanbul		Turkey	34899
104	Erciyes Uni ; Hematology	Kayseri		Turkey	38039
105	Koc Universitesi (KU) Tip Fakultesi (Koc University School of Medicine)	Sariyer		Turkey	34450
106	Karadeniz Technical Uni School of Medicine; Hematology	Trabzon		Turkey	61800
107	Sanko University Faculty of Medicine	Şehi̇tkami̇l		Turkey	27090
108	Municipal Noncommercial Institution Regional Center of Oncology	Kharkiv	Kharkiv Governorate	Ukraine	61070
109	Mykolayiv Regional Hospital	Mykolaiv	KIEV Governorate	Ukraine	54058
110	Royal Cornwall Hospitals NHS Trust	Cornwall		United Kingdom	TR1 3LJ
111	Nottingham City Hospital; Dept of Haematology	Nottingham		United Kingdom	NG5 1PB

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT04712097

Other Study ID Numbers:

GO42909
2020-005239-53

First Posted:

Jan 15, 2021

Last Update Posted:

Aug 22, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 22, 2022