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Completed

NCT Number: NCT03677141

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

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).

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Key information

Conditions

B-Cell Non-Hodgkin Lymphoma Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

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

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

for Phase Ib and Phase II Portions

  • 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

Inclusion criteria

for Phase Ib Portion

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
  • Treatment with at least one prior CD20-directed therapy
  • Group B only: no prior treatment with polatuzumab vedotin

Inclusion criteria

for Phase II Portion

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

Exclusion criteria

  • 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
  • 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

Exclusion criteria

for Phase Ib Portion

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)

Exclusion criteria

for Phase II Portion

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

Treatment and study plan

Mosunetuzumab

Drug

Participants will receive intravenous (IV) mosunetuzumab.

Polatuzumab Vedotin

Drug

Participants will receive polatuzumab vedotin via IV.

Rituxumab

Drug

Participants will receive rituxumab via IV.

Cyclophosphamide

Drug

Participants will receive cyclophosphamide via IV.

Doxorubicin

Drug

Participants will receive doxorubicin via IV.

Vincristine

Drug

Participants will receive vincristine via IV.

Prednisone

Drug

Participants will receive oral prednisone.

Tocilizumab

Drug

Participants will receive tocilizumab via IV.

Primary outcomes

  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)

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

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

Secondary outcomes

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

    Time frame: 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)

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

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

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

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

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

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

    Time frame: Up to approximately 50 months

    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.

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

    Time frame: Up to approximately 50 months

    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).

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

    Time frame: Up to approximately 50 months

    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).

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

    Time frame: 1 year

    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.

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

    Time frame: Up to 50 months

    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).

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

    Time frame: 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)

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

  11. Polatuzumab Vedotin Serum Concentrations

    Time frame: C2D1, C6D1

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

    Time frame: C1D1-C6D1

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

    Time frame: C1D1-C6D1

  14. Mosunetuzumab Serum Concentrations

    Time frame: C1D1-C5D1

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

    Time frame: 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)

    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).

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

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

    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).

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Sep 19, 2018
Registry last updated
Dec 18, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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