Diffuse Large B-cell Lymphoma Clinical Trial
Official title:
A Phase I/II Trial of Mosunetuzumab (BTCT4465A) as Consolidation Therapy in Patients With Diffuse Large B-Cell Lymphoma Following First-Line Immunotherapy and as Monotherapy or in Combination With Polatuzumab Vedotin in Elderly/Unfit Patients With Previously Untreated Diffuse Large B-Cell Lymphoma
Verified date | May 2024 |
Source | Hoffmann-La Roche |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This study will evaluate the safety, pharmacokinetics, and preliminary efficacy of mosunetuzumab following first-line diffuse large B-cell lymphoma (DLBCL) immunochemotherapy in participants with a best response of stable disease or partial response, or in elderly/unfit participants with previously untreated DLBCL, or subcutaneous mosunetuzumab in combination with polatuzumab vedotin IV in elderly/unfit participants with previously untreated DLBCL.
Status | Active, not recruiting |
Enrollment | 188 |
Est. completion date | August 3, 2025 |
Est. primary completion date | August 3, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria for All Cohorts - 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 - Adequate hematologic function - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2; with the exception of South Korea, where participants 80 years or older with ECOG >/= 2 will not be eligible Inclusion Criteria Specific to Cohort A Participants in Cohort A must also meet the following criteria for study entry: - Histologically confirmed DLBCL according to World Health Organization (WHO) 2016 expected to express the cluster of differentiation-20 (CD20) antigen - One prior therapy with any systemic anthracycline-based chemoimmunotherapy containing regimen for previously untreated DLBCL - Best response of SD or PR to prior systemic chemoimmunotherapy at the end of induction treatment in accordance with the Lugano 2014 criteria Inclusion Criteria Specific to Cohorts B and C Participants in Cohorts B and C must also meet the following criteria for study entry: - Previously untreated, histologically confirmed, DLBCL according to WHO 2016 classification - Age >/= 80 years, or - Age 65-79 years and considered ineligible for chemoimmuotherapy (R-CHOP) with at least one of the following: Impairment in at least two activity of daily living (ADL) components as defined in the protocol; impairment in at least two instrumental ADL components as defined in the protocol; cumulative illness rating scale - geriactic (CIRS-G) score of at least one cormorbidity with a severity score of 3-4 (not including lymphoma and hematologic deficiencies due to lymphoma) or a score of 2 in >/= 8 comorbidities; impairment in cardiac function, renal function, liver function, or other comorbidities such that the participant is unfit for full-dose immunochemotherapy, such as rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) - Participants with an initial ECOG performance status of 3 may be considered during screening if the performance status is DLBCL-related and if pre-phase treatment during the screening phase (not more than 100 mg/day up to 7 days prior to Cycle 1 Day 1) results in an improvement of ECOG performance status to </= 2 prior to enrollment Exclusion Criteria for All Cohorts Participants who meet any of the following criteria will be excluded from study entry: - Transformed lymphoma - CNS lymphoma - Prior treatment with mosunetuzumab - Prior stem cell transplant (autologous and allogeneic) - 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) - Known or suspected history of hemophagocytic lymphohistiocytosis (HLH) - Positive SARS-CoV-2 antigen or PCR test within 30 days prior to Cycle 1 Day 1 - Prior solid organ transplantation - Current or past history of central nervous system (CNS) disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease - Clinically significant history of liver disease - Prior treatment with radiotherapy within 2 weeks prior to Cycle 1, Day 1 (C1D1) - Significant cardiovascular disease Exclusion Criteria Specific to Cohort A Participants in Cohort A who meet the following criteria will be excluded from study entry: - Prior anti-lymphoma treatment with chemotherapy, immunotherapy, or biologic therapy 4 weeks prior to C1D1 Exclusion Criterion Specific to Cohorts B and C Participants in Cohorts B and C who meet the following criterion will be excluded from study entry: - Prior treatment for DLBCL with chemotherapy, immunotherapy, and biologic therapy Exclusion Criteria Specific to Cohort C Participants in Cohort C who meet the following criteria will be excluded from study entry: - Current Grade >1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease |
Country | Name | City | State |
---|---|---|---|
Israel | Soroka Medical Center | Beer Sheva | |
Israel | Carmel medical center | Haifa | |
Israel | Rambam Medical Center | Haifa | |
Israel | Hadassah Ein-Karem; Clinical Pharmacology Unit | Jerusalem | |
Israel | Shaare Zedek Medical Center | Jerusalem | |
Israel | Meir Medical Center | Kfar- Saba | |
Israel | Laniado Hospital-Sanz Medical Center | Netanya | |
Israel | Rabin Medical Center-Beilinson Campus | Petach Tikva | |
Israel | Sheba Medical Center | Ramat Gan | |
Israel | Kaplan Medical Center | Rehovot | |
Israel | Tel Aviv Sourasky Medical Center; Pharmacy | Tel Aviv | |
Korea, Republic of | Pusan National University Hospital | Busan | |
Korea, Republic of | Keimyung University Dongsan Hospital | Daegu | |
Korea, Republic of | Gachon University Gil Medical Center | Incheon | |
Korea, Republic of | Samsung Medical Center | Seoul | |
Korea, Republic of | Seoul National University Hospital | Seoul | |
Korea, Republic of | Severance Hospital, Yonsei University | Seoul | |
Korea, Republic of | The Catholic University of Korea Yeouido St. Mary's Hospital; Hematology-Oncology | Seoul | |
Poland | Uniwersyteckie Centrum Kliniczne | Gdansk | |
Poland | Szpitale Pomorskie Sp. z o. o. | Gdynia | |
Poland | PRATIA MCM Kraków | Kraków | |
Poland | Centrum Onkologii Ziemi Lubelskiej im. ?w. Jana z Dukli | Lublin | |
Poland | Szpital Wojewodzki w Opolu;Pododdz. Gastroenter., Pododdz. Hematologii | Opole | |
Poland | Instytut Hematologii i Transfuzjologii; Klinika Hematologii | Warszawa | |
Spain | Hospital Universitario Vall d Hebron | Barcelona | |
Spain | Hospital San Pedro de Alcantara; Servicio de Hematología | Caceres | |
Spain | Institut Catala d Oncologia Hospitalet | Hospitalet de Llobregat | Barcelona |
Spain | Hospital General Universitario Gregorio Marañon | Madrid | |
Spain | Hospital Universitario 12 de Octubre | Madrid | |
Spain | Hospital Universitario Virgen Macarena | Seville | Sevilla |
Spain | Hospital Universitari i Politecnic La Fe | Valencia | |
Taiwan | Taipei Medical University ?Shuang Ho Hospital | New Taipei City | |
Taiwan | Chi-Mei Hospital, Liouying | Tainan | |
Taiwan | National Cheng Kung University Hospital; Oncology | Tainan | |
Taiwan | Mackay Memorial Hospital | Taipei | |
Taiwan | National Taiwan University Hospital | Taipei | |
Taiwan | Taipei Veterans General Hospital | Taipei City | |
United States | University of Michigan | Ann Arbor | Michigan |
United States | University of Maryland Medical Center | Baltimore | Maryland |
United States | University of Alabama at Birmingham School of Medicine | Birmingham | Alabama |
United States | Rush University Medical Center; Rush University Cancer Center | Chicago | Illinois |
United States | Texas Oncology - Baylor Charles A. Sammons Cancer Center | Dallas | Texas |
United States | Duke University | Durham | North Carolina |
United States | Fort Wayne Medical Institute | Fort Wayne | Indiana |
United States | Norton Medical Plaza II; Norton Cancer Institute | Louisville | Kentucky |
United States | Miami Cancer Institute of Baptist Health, Inc. | Miami | Florida |
United States | University of Miami Sylvester Comprehensive Center | Miami | Florida |
United States | Sloan Kettering Cancer Center | New York | New York |
United States | Fox Chase Cancer Center | Philadelphia | Pennsylvania |
United States | Providence Portland Medical Center | Portland | Oregon |
United States | Rhode Island Hospital | Providence | Rhode Island |
United States | University of California, Los Angeles (UCLA) - Hematology/Oncology Santa Monica | Santa Monica | California |
United States | Moffitt Cancer Center Screening and Prevention | Tampa | Florida |
Lead Sponsor | Collaborator |
---|---|
Hoffmann-La Roche |
United States, Israel, Korea, Republic of, Poland, Spain, Taiwan,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Percentage of Participants with Adverse Events | Baseline through approximately 90 days after last study treatment | ||
Primary | Positron Emission Tomography-Computed Tomography (PET-CT) Complete Response (CR) Rate at Time of Primary Response Assessment (PRA) According to Lugano 2014 Response Criteria (Cohort A) | 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days) | ||
Primary | PET-CT Objective Response Rate (ORR) at PRA According to Lugano 2014 Response Criteria as Determined by the Investigator (Cohort B) | 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days) | ||
Primary | PET-CT ORR at PRA According to the Lugano 2014 Criteria as Determined by an Independent Review Committee (IRC) (Cohort C) | 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days) | ||
Secondary | Maximum Serum Concentration (Cmax) of Mosunetuzumab IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Minimum Serum Concentration (Cmin) of Mosunetuzumab IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Area Under the Curve (AUC) of Mosunetuzumab IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Clearance (CL) of Mosunetuzumab IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Volume of Distribution at Steady State (Vss) of Mosunetuzumab IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Maximum Serum Concentration (Cmax) of Mosunetuzumab SC | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Time to Maximum Serum Concentration (Tmax) of Mosunetuzumab SC | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Minimum Serum Concentration (Cmin) of Mosunetuzumab SC | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Area Under the Curve (AUC) of Mosunetuzumab SC | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Clearance (CL) of Mosunetuzumab SC | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Volume of Distribution at Steady State (Vss) of Mosunetuzumab SC | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Maximum Serum Concentration (Cmax) of Polatuzumab Vedotin IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Minimum Serum Concentration (Cmin) of Polatuzumab Vedotin IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Area Under the Curve (AUC) of Polatuzumab Vedotin IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Clearance (CL) of Polatuzumab Vedotin IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Volume of Distribution at Steady State (Vss) of Polatuzumab Vedotin IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | End of Infusion Concentration (Ceoi) of Polatuzumab Vedotin IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Trough Concentration (Ctrough) of Polatuzumab Vedotin IV | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | PET-CT Rate According to the Lugano 2014 Criteria at PRA as Determined by the Investigator (Cohorts B and C) and IRC (Cohort C) | 6-8 weeks after Cycle 8 Day 1 or the final dose of study treatment (cycle = 21 days) | ||
Secondary | Objective Response Rate (ORR), Defined as the Proportion of Participants with a Complete Response (CR) or Partial Response (PR) at PRA as Determined by the Investigator (Cohorts A and C) | Baseline through 2 years after PRA (up to a total of approximately 2.5 years) | ||
Secondary | Best ORR (CR or PR at any time) During the Study Based on PET-CT and/or CT Scans as Determined by the Investigator (All Cohorts) and by IRC (Cohort C) | Baseline through 2 years after PRA (up to a total of approximately 2.5 years) | ||
Secondary | Duration of Response (DOR) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C) | From the first occurrence of a documented objective response to disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years) | ||
Secondary | Duration of Confirmed Response (DOCR) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C) | From the first occurrence of a documented CR to disease progression or relapse, or death from any cause, whichever occurs first (up to approximately 2.5 years) | ||
Secondary | Progression-Free Survival (PFS) as Determined by the Investigator (All Cohorts) and by IRC (Cohort C) | From the first study treatment to the first occurrence of disease progression, relapse, or death, whichever occurs first (up to approximately 2.5 years) | ||
Secondary | Overall Survival (OS) | From the first study treatment to death from any cause | ||
Secondary | Time to Deterioration in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Physical Functioning and Fatigue (Cohorts B and C) | From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years) | ||
Secondary | Time to Deterioration in European Organization for Research and Treatment of Cancer Item Library (EORTC-IL17) Physical Functioning (Cohorts B and C) | From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years) | ||
Secondary | Time to Deterioration in the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale (Cohorts B and C) | From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years) | ||
Secondary | Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC QLQ-C30 (Cohorts B and C) | From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years) | ||
Secondary | Proportion of Participants Achieving a Clinically Meaningful Improvement in Physical Functioning as Measured by EORTC IL17 (Cohorts B and C) | From the first study treatment to the first occurrence of disease progression, relapse, initiation of new anti-lymphoma treatment, or death from any cause, whichever occurs first (up to approximately 2.5 years) | ||
Secondary | Anti-Drug Antibodies (ADAs) to Mosunetuzumab | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) | ||
Secondary | Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin (Cohort C) | At pre-defined intervals from Cycle 1 Day 1 through approximately 90 days after the last study treatment (cycle = 21 days) |
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