AzTrials
AzTrials

B-cell Non-Hodgkin LymphomaPhase 1/2NCT03677141

A Phase Ib/II Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Participants With B-Cell Non-Hodgkin Lymphoma

A Phase 1/2 study testing Mosunetuzumab, Polatuzumab Vedotin and Rituxumab in people with B-cell Non-Hodgkin Lymphoma, run by Hoffmann-La Roche at 41 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (M-CHOP) and, subsequently, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) plus polatuzumab vedotin (CHP-pola) in… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
B-cell Non-Hodgkin Lymphoma
What is being tested?
Mosunetuzumab, Polatuzumab Vedotin and Rituxumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
117 participants
Where
41 sitesin 6 countries
Study dates
8 Mar 2019to 12 Oct 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest diameter
  • Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
  • Adequate hematologic function
  • Participants must also meet the following criteria for study entry into the Phase Ib portion:
  • Histologically confirmed B-cell NHL according to the World Health Organization (WHO) 2016 classification expected to express the cluster of differentiation-20 (CD20) antigen
  • Relapsed or refractory (R/R) B-cell NHL after at least one prior systemic lymphoma therapy
Show all 11Show fewer
  • Treatment with at least one prior CD20-directed therapy
  • Group B only: no prior treatment with polatuzumab vedotin
  • Participants must also meet the following criteria for study entry in the Phase II portion:
  • Previously untreated, histologically confirmed DLBCL according to WHO 2016 classification
  • International Prognostic Index (IPI) score of 2-5

Who cannot join

  • Prior treatment with mosunetuzumab
  • Prior allogenic stem-cell transplant
  • Current Grade >1 peripheral neuropathy
  • Participants with history of confirmed progressive multifocal leukoencephalopathy (PML)
  • Known or suspected chronic active Epstein Barr virus (CAEBV), hepatitis B, hepatitis C (HCV), or Human Immunodeficiency Virus (HIV)
  • Prior solid organ transplantation
Show all 20Show fewer
  • History of autoimmune disease
  • Current or past history of central nervous system (CNS) lymphoma
  • Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
  • Significant cardiovascular disease or pulmonary disease
  • Clinically significant history of liver disease
  • Recent major surgery within 4 weeks before the start of C1D1, other than superficial lymph node biopsies for diagnosis
  • Participants who also meet any of the following criteria will be excluded from study entry in the Phase Ib portion:
  • Prior treatment with chemotherapy, immunotherapy, and biologic therapy 4 weeks prior to C1D1
  • Prior treatment with radiotherapy within 2 weeks prior to C1D1
  • Adverse events from prior anti-cancer therapy resolved to ≤Grade 1 (with the exception of alopecia and anorexia)
  • Prior treatment with >250 mg/m^2 doxorubicin (or equivalent anthracycline dose)
  • Participants who also meet any of the following criteria will be excluded from study entry in the Phase II portion:
  • Participants with transformed lymphoma
  • Prior therapy for B-cell NHL

Trial locations and contacts

41 sites in 6 countries.

41 sites in 6 countries

United States15 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • University of Alabama Birmingham

    Birmingham, Alabama, 35233

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030-4009

  • University of California; Moores Cancer Center

    La Jolla, California, 92093

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

  • Medical College of Wisconsin, Inc.

    Milwaukee, Wisconsin, 53226-3596

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Rhode Island Hospital

    Providence, Rhode Island, 02903-4923

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica

    Santa Monica, California, 90404-2023

  • Scott and White Hospital; Cancer Center

    Temple, Texas, 76508

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

  • University of Kansas Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

Spain8 sites

  • Institut Catala d?Oncologia Hospital Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 8041

  • Hospital San Pedro de Alcantara; Servicio de Hematología

    Cáceres, 10003

  • Hospital General Universitario Gregorio Marañon

    Madrid, 28007

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario La Paz

    Madrid, 28046

  • Clinica Universidad de Navarra

    Pamplona, Navarre, 31008

  • Hospital Universitario Virgen Macarena

    Seville, Sevilla, 41071

Other trials in Spain

France5 sites

  • CHU Henri Mondor; Service d'Oncologie Medicale

    Créteil, 94010

  • Centre Leon Berard

    Lyon, 69008

  • Hôpital Saint-Louis

    Paris, 75475

  • Centre Henri Becquerel- Centre de Lutte Contre le Cancer

    Saint-Herblain, 44805

  • Gustave Roussy

    Villejuif, 94805

Other trials in France

Poland5 sites

  • Maria Sklodowska-Curie Memorial Cancer Centre

    Gliwice, 44-102

  • Ma?opolskie Centrum Medyczne

    Krakow, 30-501

  • Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka

    Słupsk, 76-200

  • Instytut Hematologii i Transfuzjologii; Klinika Zaburze? Hemostazy i Chorób Wewn?trznych

    Warsaw, 02-776

  • Katedra i Klinika Hematologii; Nowotworów Krwi i Transplantacji Szpiku

    Wroc?aw

Other trials in Poland

Austria4 sites

  • Uniklinikum Salzburg, LKH; Univ.Klinik f. Innere Medizin III der PMU

    Salzburg, 5020

  • LKH Steyr

    Steyr, 4400

  • Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien

    Vienna, 1090

  • Hanusch-Krankenhaus

    Vienna, 1140

Other trials in Austria

South Korea4 sites

  • Pusan National University Yangsan Hospital

    Gyeongsangnam-do, 50612

  • Seoul National University Hospital

    Seoul, 03080

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

About this study

Official title: A Phase Ib/II, Open-Label, Multicenter, Randomized, Controlled Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination With CHOP or CHP-Polatuzumab Vedotin in Patients With B-Cell Non-Hodgkin Lymphoma

This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (M-CHOP) and, subsequently, in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) plus polatuzumab vedotin (CHP-pola) in participants with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), and in previously untreated participants with diffuse large B-cell lymphoma (DLBCL).

Being tested
Mosunetuzumab, Polatuzumab Vedotin, Rituxumab, Cyclophosphamide, Doxorubicin
Medical subject headings
Lymphoma, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MosunetuzumabDrug

    Participants will receive intravenous (IV) mosunetuzumab.

  • Polatuzumab VedotinDrug

    Participants will receive polatuzumab vedotin via IV.

  • RituxumabDrug

    Participants will receive rituxumab via IV.

  • CyclophosphamideDrug

    Participants will receive cyclophosphamide via IV.

  • DoxorubicinDrug

    Participants will receive doxorubicin via IV.

  • VincristineDrug

    Participants will receive vincristine via IV.

  • PrednisoneDrug

    Participants will receive oral prednisone.

  • TocilizumabDrug

    Participants will receive tocilizumab via IV.

Study groups in NCT03677141
Study groupRoleWhat they receive
Phase Ib: Mosunetuzumab (M)-CHOP Dose FindingExperimentalParticipants will receive M-CHOP up to the phase II recommended dose (RP2D).
Receives: Drug: Mosunetuzumab; Drug: Polatuzumab Vedotin; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Tocilizumab
Phase Ib: M-CHP-Pola Dose-FindingExperimentalParticipants will receive M-CHP-Pola up to the RP2D.
Receives: Drug: Mosunetuzumab; Drug: Polatuzumab Vedotin; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Tocilizumab
Phase II: M-CHOP Previously Untreated (1L) DLBCL Safety CohortExperimentalParticipants with 1L DLBCL will receive mosunetuzumab at the RP2D in combination with CHOP.
Receives: Drug: Mosunetuzumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Tocilizumab
Phase II: M-CHP-Pola 1L DLBCLExperimentalParticipants with 1L DLBCL will receive M-CHP-Pola at a dose determined in the dose finding stage.
Receives: Drug: Mosunetuzumab; Drug: Polatuzumab Vedotin; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Tocilizumab
Phase II: Rituxumab (R)-CHP-Pola 1L DLBCLActive comparatorParticipants with 1L DLBCL will receive R-CHP-Pola at a dose determined in the dose finding stage.
Receives: Drug: Polatuzumab Vedotin; Drug: Rituxumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone
Phase II: M-CHOP 1L DLBCLExperimentalParticipants with 1L DLBCL will receive M-CHOP at a dose determined in the dose finding stage. NOTE: No participants were enrolled to this arm.
Receives: Drug: Mosunetuzumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Tocilizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete Response (CR) Rate at the Time of Primary Response Assessment (PRA) Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Determined by Independent Review Committee (IRC)

    The CR rate was defined as the percentage of participants with CR. Assessments were made according to the Lugano 2014 Response Criteria.

    Measured: 6-8 weeks after either C6D1 or last dose of study treatment

Secondary outcomes (16)

  1. CR Rate at PRA Based on CT Only as Determined by the Investigator (Phase II)

    Measured: 6-8 weeks after C6D1 or last dose of study treatment

  2. Overall Response Rate (ORR) at PRA Based on PET-CT as Determined by the Investigator (Phase II)

    ORR is defined as a CR or PR at the time of primary assessment based on PET-CT, as determined by the investigator.

    Measured: 6-8 weeks after C6D1 or last dose of study treatment

  3. ORR at PRA Based on CT Only as Determined by the Investigator (Phase II)

    ORR is defined as a CR or PR at the time of primary assessment based on CT only, as determined by the investigator.

    Measured: 6-8 weeks after C6D1 or last dose of study treatment

  4. Best ORR Based on PET-CT and/or CT Scan as Determined by the Investigator (Phase II)

    Best ORR was defined as CR or PR at any time on study and based on PET-CT or CT only as determined by the investigator.

    Measured: Up to approximately 50 months

  5. Duration of Response (DOR) as Determined by the Investigator (Phase II)

    DOR is defined as the time from the first occurrence of a documented objective response to disease progression or relapse as determined by the investigator, or death from any cause, whichever occurs first. The range values (min-max) are based on censored observations (if a participant did not experience disease progression or death prior to the end of the trial DOR was censored on the date of the last tumor assessment).

    Measured: Up to approximately 50 months

  6. Progression-free Survival (PFS) as Determined by the Investigator (Phase II)

    PFS is defined as the time from randomization to the first occurrence of disease progression or relapse as determined by the investigator, or death from any cause, whichever occurs first. The earliest contributing event to PFS is reported. The range (min-max) values are based on censored observations (participants without a baseline-evaluable tumor assessment were censored at the date of randomization or first study treatment, plus 1 day).

    Measured: Up to approximately 50 months

  7. PFS at 1 Year as Determined by the Investigator (Phase II)

    PFS at 1 year is defined as the proportion of participants with disease progression or relapse as determined by the investigator, or death from any cause within 1 year of randomization.

    Measured: 1 year

  8. Event-free Survival (EFS) as Determined by the Investigator (Phase II)

    EFS is defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator, initiation of new anti-lymphoma therapy (NALT), or death from any cause, whichever occurs first. The range values (min-max) are based on censored observations (if a participant did not experience disease progression or death prior to the end of the trial DOR was censored on the date of the last tumor assessment).

    Measured: Up to 50 months

  9. Time to Deterioration in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale

    Measured: C1D1 through follow-up period (to begin 2 years after PRA or at the time of study drug discontinuation)

  10. Time to Deterioration in Physical Functioning and Fatigue as Measured by the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTC QLQ-C30)

    Measured: C1D1 through follow-up period (to begin 2 years after PRA or at the time of study drug discontinuation)

  11. Polatuzumab Vedotin Serum Concentrations

    Measured: C2D1, C6D1

  12. Polatuzumab Vedotin Antibody-conjugated Monomethyl Auristatin E (acMMAE) Serum Concentrations

    Measured: C1D1-C6D1

  13. Polatuzumab Vedotin Unconjugated Mono-methyl Auristatin E (MMAE) Serum Concentrations

    Measured: C1D1-C6D1

  14. Mosunetuzumab Serum Concentrations

    Measured: C1D1-C5D1

  15. Baseline Prevalence and Incidence of Treatment Emergent Anti-drug Antibodies (ADA) to Mosunetuzumab

    Participants are considered to have treatment-induced ADA responses if they are ADA negative or missing data at baseline and then develop an ADA response following study drug administration. Participants are considered to have treatment-enhanced ADA responses if they are ADA positive at baseline and the titer of one or more post baseline samples is at least 4-fold greater than the titer of the baseline sample. Patients are considered to be negative for ADAs if they are ADA negative at all timepoints or if they are ADA positive at baseline but do not have any post-baseline samples with a titer that is at least 4-fold greater than the titer of the baseline sample (treatment unaffected).

    Measured: Cycles 1, 2, 6, 16, and at early discontinuation visit or at PRA (6-8 weeks after either C6D1 or last dose of study treatment)

  16. Baseline Prevalence and Incidence of Treatment Emergent ADA to Polatuzumab Vedotin

    Participants are considered to have treatment-induced ADA responses if they are ADA negative or missing data at baseline and then develop an ADA response following study drug administration. Participants are considered to have treatment-enhanced ADA responses if they are ADA positive at baseline and the titer of one or more post baseline samples is at least 4-fold greater than the titer of the baseline sample. Patients are considered to be negative for ADAs if they are ADA negative at all timepoints or if they are ADA positive at baseline but do not have any post-baseline samples with a titer that is at least 4-fold greater than the titer of the baseline sample (treatment unaffected).

    Measured: Cycles 1, 2, 6, and at early discontinuation visit or at PRA (6-8 weeks after either C6D1 or last dose of study treatment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2018
  2. Study start8 Mar 2019
  3. Primary completion12 Oct 2023
  4. Study completion12 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
117 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03677141
Sponsor's protocol ID
GO40515
Other IDs
2018-001039-29, 2018
Status last verified
Nov 2024
First submitted
11 Sep 2018
Last updated
18 Dec 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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).

Publications

  • Westin J, Phillips TJ, Mehta A, Hoffmann MS, Gonzalez-Barca E, Thieblemont C, Bastos-Oreiro M, Greil R, Giebel S, Wei MC, Wang J, Bucher R, Sit J, Penuel E, Purev E, Yee DL, Bergua-Burgues JM. Mosunetuzumab plus Pola-CHP compared with Pola-R-CHP in previously untreated DLBCL: final results from a phase 2 study. Blood Adv. 2025 May 27;9(10):2461-2472. doi: 10.1182/bloodadvances.2024014907.

    PubMed 39908481

  • Olszewski AJ, Phillips TJ, Hoffmann MS, Armand P, Kim TM, Yoon DH, Mehta A, Greil R, Westin J, Lossos IS, Munoz JL, Sit J, Wei MC, Yang A, Chen V, Purev E, Yee DL, Jaeger U. Mosunetuzumab in combination with CHOP in previously untreated DLBCL: safety and efficacy results from a phase 2 study. Blood Adv. 2023 Oct 24;7(20):6055-6065. doi: 10.1182/bloodadvances.2023010840.

    PubMed 37581593

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Mosunetuzumab, Polatuzumab Vedotin and Rituxumab in people with B-cell Non-Hodgkin Lymphoma, run by Hoffmann-La Roche at 41 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in United States, Spain, France, Poland, Austria and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Response (CR) Rate at the Time of Primary Response Assessment (PRA) Based on Positron Emission Tomography - Computed Tomography (PET-CT) as Determined by Independent Review Committee (IRC) (time frame: 6-8 weeks after either C6D1 or last dose of study treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03677141, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in