Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Non-Hodgkin

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

B-cell Lymphoma

Lymphosarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Anti-Infective Agents

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Obinutuzumab

Prednisone

Rituximab

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Polatuzumab vedotin

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunoconjugates

Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.

Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.

Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.

Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.

Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m\^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Doxorubicin will be administered at 50 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Obinutuzumab will be administered at 1000 milligrams (mg) IV on Cycle 1 Days 1, 8, and 15 and on Day 1 of Cycles 3-8.

Polatuzumab vedotin will be administered at escalating doses (at a starting dose of 1 mg/kg) IV every 3 weeks, for 6 or 8 cycles.

Polatuzumab Vedotin

Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

Prednisone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.

Rituximab will be administered at 375 mg/m\^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.

Clinical Trials

This multicenter, open-label, dose-escalation study will evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of polatuzumab vedotin in combination with rituximab or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone (CHP chemotherapy) in participants with non-Hodgkin's lymphoma (NHL). Participants will receive escalating doses of polatuzumab vedotin intravenously (IV) every 3 weeks in combination with standard doses of rituximab plus CHP chemotherapy (R-CHP) or obinutuzumab plus CHP chemotherapy (G-CHP). Participants will be treated for a total of six or eight cycles in accordance with local institutional practice. Two parallel treatment arms will explore doses of polatuzumab vedotin in combination with R-CHP or G-CHP. The maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of polatuzumab vedotin in combination with R-CHP will be identified before it is combined with G-CHP. Once the MTD or RP2D is determined, polatuzumab vedotin will be dosed at MTD or RP2D -1 in combination with G-CHP to start the dose escalation of this combination.

A Study of Polatuzumab Vedotin in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Participants With B-Cell Non-Hodgkin's Lymphoma

A Phase Ib/II Study Evaluating the Safety, Tolerability and Anti-Tumor Activity of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Patients With B-Cell Non-Hodgkin's Lymphoma

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).

All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD.

Complete Response (CR) rate was defined as the percentage of participants with CR at the end of treatment, as assessed by the investigator, with and without FDG-PET. The overall response rate was defined as the percentage of participants with CR or PR at the end of treatment, as assessed by the investigator, with and without FDG-PET.

The Anti-Drug Antibody (ADA) screening assay was optimized to tolerate drug interference and was able to detect 90 and 500 ng/mL of the positive control sample in the presence of 20 μg/mL of polatuzumab vedotin. Polatuzumab vedotin total antibody concentrations were determined for each ADA sample. Out of a total of 186 ADA samples that were measured for polatuzumab vedotin total antibody, 184 samples had levels less than 20 μg/mL. Polatuzumab vedotin total antibody concentrations ranged from \<0.050 μg/mL to 52.1 μg/mL with a median concentration of 3.38 μg/mL.

The ADA screening assay was optimized to tolerate drug interference and was able to detect 500 ng/mL of the ADA-positive control sample in the presence of 50 micrograms/mL of obinutuzumab. Obinutuzumab concentrations were determined for each ADA sample. Out of a total of 48 ADA samples that were measured for obinutuzumab, 9 samples had levels less than 50 micrograms/mL of obinutuzumab. Obinutuzumab concentrations in ADA samples ranged from 0.282 micrograms/mL to 522 micrograms/mL with a median concentration of 210 micrograms/mL. Therefore, it is possible that samples with obinutuzumab concentrations greater than 50 micrograms/mL might be false negative for ADA.

AUC information for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.

Cmax for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.

CL for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.

t1/2 for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.

Vss for Polatuzumab Vedotin was estimated from serum concentration data using non-compartmental analysis.

Plasma levels of cyclophosphamide will be assessed and compared at the same timepoints of Cycle 1 (in the absence of polatuzumab vedotin) and Cycle 3 (in the presence of polatuzumab vedotin), and compared with historical data to evaluate potential PK interactions with polatuzumab vedotin.

Plasma levels of doxorubicin will be assessed and compared at the same timepoints of Cycle 1 (in the absence of polatuzumab vedotin) and Cycle 3 (in the presence of polatuzumab vedotin), and compared with historical data to evaluate potential PK interactions with polatuzumab vedotin.

The TINAS is an 11-item questionnaire scored on a 0 to 10 scale, with 0 being the symptom is not present to 10 being the symptom is as bad as the participant can imagine. The questionnaire will be analyzed for the individual neuropathy symptoms experienced by a participant as well as the calculation of an overall neuropathy severity score. The TINAS scale will be completed daily over the course of study treatment. Additionally, to collect information about the reversibility of peripheral neuropathy, the TINAS will be completed once a week for the first 2 months, then once a month for the next 10 months following treatment completion. Results are only being reported here up until the End of Treatment visit (duration of Study treatment).

The TINAS is an 11-item questionnaire scored on a 0 to 10 scale, with 0 being the symptom is not present to 10 being the symptom is as bad as the patient can imagine. The questionnaire will be analyzed for the individual neuropathy symptoms experienced by a participant as well as the calculation of an overall neuropathy severity score. The TINAS scale will be completed daily over the course of study treatment. Additionally, to collect information about the reversibility of peripheral neuropathy, the TINAS will be completed once a week for the first 2 months, then once a month for the next 10 months following treatment completion. Additionally, a single item that asks patients to rate when numbness and tingling was at the worst will be used to predict the onset of peripheral neuropathy. The measure takes less than 5 minutes to complete. Results are only being reported here up until the End of Treatment visit (duration of Study treatment).

Time from the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse or death from any cause (PFS), as assessed by the investigator for the subgroup of participants with a best overall response of CR or PR. For participants achieving a response who did not experience disease progression, relapse, or died prior to the time of the analysis, the DOR was censored on the date of last disease assessment.

Time from date of first dose of study drug (Day 1) to the first occurrence of progression or relapse, or death from any cause while in the study, as assessed by the investigator. If a participant did not experience progressive disease or death, PFS was censored on the day of the last tumor assessment. If a post-baseline assessment was not available, PFS was censored on Day 1.

Time from randomization to disease progression or relapse, as assessed by the investigator, death from any cause, or initiation of any new anti-lymphoma therapy (NALT). If the specified event (disease progression or relapse, death, initiation of a NALT) did not occur, EFS was censored at the date of last tumor assessment. For participants without an event who did not have post-baseline tumor assessments, EFS was censored at the time of randomization.

Relative dose intensity (DI) was defined as the ratio of the amount of a drug actually administered (actual DI) to the amount planned (planned DI) for a fixed time period, expressed as a percentage.

The time from the date of randomization to the date of death from any cause. For participants who did not die at the time of the analyses, OS was censored on the last date when the participants were known to be alive.

Genentech, Inc.

The safety population was defined as all participants who received at least one dose of study medication. AEs that were entered into the data base at the time of the data base lock were included in the AE analysis.

Polatuzumab Vedotin (1.0mg) + R-CHP

Polatuzumab Vedotin (1.4mg) + R-CHP

Polatuzumab Vedotin (1.8mg) + R-CHP

Dose Escalation: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. The participant in this group was incorrectly dosed on 2.4mg Pola R-CHP group and should have been assigned to the 1.8mg Pola R-CHP group.

Polatuzumab Vedotin (2.4mg) + R-CHP

Polatuzumab Vedotin (1.4mg) + G-CHP

Polatuzumab Vedotin (1.8mg) + G-CHP

Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP. Participants treated with MTD determined from dose escalation cohorts.

Expansion: Polatuzumab Vedotin (1.8mg) + R-CHP

Dose Expansion: Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP. Participants treated with MTD determined from dose escalation cohorts.

Expansion: Polatuzumab Vedotin (1.8mg) + G-CHP

Total

Age, Continuous

Sex: Female, Male

Not Hispanic or Latino

Not Stated

Unknown

Race/Ethnicity, Customized

Black or African American

Other

White

Medical Communications

The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL.

Number of Participants With Adverse Events in Diffuse Large B-Cell Lymphoma (DLBCL) Population

The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with Non-DLBCL.

Number of Participants With Adverse Events in Non-DLBCL Population

Number of Participants With Dose Limiting Toxicities (DLTs) in DLBCL Population

Number of Participants With DLTs in Non-DLBCL Population

Complete Response (CR)

Partial Response (PR)

Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for DLBCL Population

Percentage of Participants With Objective Response (CR or Partial Response [PR]), as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population

The safety population was defined as all participants who have received at least one dose of study medication. Results were reported for participants with DLBCL and Non-DLBCL.

Number of Participants With Anti-Polatuzumab Vedotin Antibodies

Number of Participants With Anti-Obinutuzumab Antibodies

Area Under the Concentration-Time Curve (AUC) of Polatuzumab Vedotin

Maximum Concentration (Cmax) of Polatuzumab Vedotin

Clearance (CL) of Polatuzumab Vedotin

Terminal Half-Life (t1/2) of Polatuzumab Vedotin

Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin

C1D1 0.5hr POSTDOSE

C1D1 3.5hr POSTDOSE

C1D1 23.5hr POSTDOSE

C3D1 0.5hr POSTDOSE

C3D1 3.5hr POSTDOSE

C3D1 23.5hr POSTDOSE

The safety population was defined as all participants who have received at least one dose of study medication. Plasma levels of cyclophosphamide were only assessed in the 'Expansion' cohorts and only participants for whom data were collected are included in the analysis.

Plasma Levels of Cyclophosphamide

C1D1 2hr POSTDOSE

C1D1 24hr POSTDOSE

C3D1 2hr POSTDOSE

C3D1 24hr POSTDOSE

The safety population was defined as all participants who have received at least one dose of study medication. Plasma levels of doxorubicin were only assessed in the 'Expansion' cohorts and only participants for whom data were collected are included in the analysis.

Plasma Levels of Doxorubicin

Baseline

Week 1

Week 2

Week 3

Week 4

Week 5

Week 6

Week 7

Week 8

Week 9

Week 10

Week 11

Week 12

Week 13

Week 14

Week 15

Week 16

Week 17

Week 18

Week 19

Week 20

Week 21

Week 22

The safety population was defined as all participants who have received at least one dose of study medication. TINAS was only assessed in the 'Expansion' cohorts and only participants for whom data were collected are included in the analysis.

Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score

Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score

Duration of Response, as Assessed by Investigator Using Cheson Criteria for DLBCL Population

Duration of Response, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population

Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population

Progression Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population

Event Free Survival, as Assessed by Investigator Using Cheson Criteria for DLBCL Population

Event Free Survival, as Assessed by Investigator Using Cheson Criteria for Non-DLBCL Population

Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for DLBCL Population

Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) for Non-DLBCL Population

Overall Survival for DLBCL Population

Overall Survival for Non-DLBCL Population

Overall Study

Symptoms and General Pathology

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Atezolizumab

Immune Checkpoint Inhibitors

Participants will receive BTCT4465A (Mosunetuzumab) via intravenous (IV) infusion or subcutaneous (SC) injection as a single-agent or in combination with atezolizumab. Dose escalation will be guided by the observed incidence of DLTs at each dose level.

Participants will receive BTCT4465A (Mosunetuzumab) as a single-agent or in combination with atezolizumab.

Participants with B-cell NHL and CLL will receive BTCT4465A (Mosunetuzumab) via IV infusion.

BTCT4465A (Mosunetuzumab) IV

Participants assigned to an atezolizumab combination group will receive atezolizumab 1200 mg administered as an IV infusion in combination with BTCT4465A (Mosunetuzumab).

Participants with B-cell NHL and CLL will receive BTCT4465A (Mosunetuzumab) via SC injection.

BTCT4465A (Mosunetuzumab) SC

This is a Phase 1/2 dose-escalation study of BTCT4465A (Mosunetuzumab) administered as a single agent and in combination with atezolizumab in participants with relapsed or refractory B-cell NHL and CLL. The study will consist of a dose-escalation stage and an expansion stage where participants will be enrolled into indication-specific cohorts.

A Safety, Efficacy and Pharmacokinetic Study of BTCT4465A (Mosunetuzumab) as a Single Agent and Combined With Atezolizumab in Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

An Open-Label, Multicenter, Phase I/II Trial Evaluating the Safety, Efficacy, and Pharmacokinetics of Escalating Doses of Mosunetuzumab (BTCT4465A) as a Single Agent and Combined With Atezolizumab in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia

The Functional Assessment of Cancer Therapy-Lymphoma (FACT-lym) Subscale, and the EuroQol 5 Dimension-5 Level (EQ-5D-5L) Questionnaire scores will also be used to assess HRQoL

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Polatuzumab Vedotin in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Participants With B-Cell Non-Hodgkin's Lymphoma	NCT01992653	Lymphoma, Non H...	Cyclophosphamid... Doxorubicin Obinutuzumab Polatuzumab Ved... Prednisolone Prednisone Rituximab	18 Years -	Genentech, Inc.
A Safety, Efficacy and Pharmacokinetic Study of BTCT4465A (Mosunetuzumab) as a Single Agent and Combined With Atezolizumab in Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)	NCT02500407	Lymphocytic Leu... Lymphoma, Non H...	BTCT4465A (Mosu... Atezolizumab BTCT4465A (Mosu...	18 Years -	Genentech, Inc.
An Observational Study of Treatment, Outcomes, and Prognosis in Patients With Follicular Non-Hodgkin's Lymphoma	NCT00097565	Lymphoma, Non H...		18 Years -	Genentech, Inc.
MabRella Study: A Study to Evaluate the Safety of Switching From Intravenous to Subcutaneous Administration of Rituximab During First-Line Treatment for Lymphoma	NCT01987505	Lymphoma, Non H...	Rituximab	18 Years - 80 Years	Hoffmann-La Roche

Spots Global Cancer Trial Database for lymphoma, non hodgkin