A Study of Escalating Doses of DCDS0780A in Participants With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma

Non-Hodgkin's Lymphoma Clinical Trial

Official title:

An Open-label, Multicenter, Phase 1/1b Dose Escalation Study Evaluating the Pharmacokinetics, Safety, Tolerability, and Preliminary Efficacy of DCDS0780A, Alone or in Combination With Rituximab, or Obinutuzumab, in Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02453087
• Other study ID #: GO29687
• Status: Completed
• Phase: Phase 1
• Start date: August 4, 2015
• Est. completion date: July 12, 2019

Study information

• Verified date: August 2019
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This open-label, multicenter, Phase 1/1b study will evaluate the safety, tolerability, and pharmacokinetics of increasing doses of DCDS0780A in participants with relapsed or refractory B-cell non-Hodgkin's lymphoma. In the combination portion of the study, the safety and tolerability of DCDS0780A in combination with rituximab or obinutuzumab will be assessed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: July 12, 2019
• Est. primary completion date: July 12, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Life expectancy of at least 12 weeks

• Histologically confirmed B-cell non-Hodgkin's lymphoma that has relapsed after or failed to respond to at least one prior treatment regimen and for which no suitable therapy of curative intent or higher priority exists

• A clinical indication for treatment as determined by the investigator

• Availability of archival or freshly collected tumor tissue before study enrollment

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Fasting (greater than or equal to [>=] 8 hours) glucose less than or equal to (<=) 160 milligrams per deciliter (mg/dL)

• Participants requiring anti-diabetic medications must be on a stable dose and regimen for >=4 weeks

• Adequate hematologic function without growth factor or transfusion support

• For women who are not postmenopausal (>= 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods as specified in protocol

• For men: agreement to remain abstinent or use a condom plus an additional contraceptive method as specified in protocol

Exclusion Criteria:

• Prior use of any monoclonal antibody or antibody-drug conjugate within 4 weeks before Cycle 1, Day 1

• Treatment with radiotherapy, any chemotherapeutic agent, systemic steroids used as an anti-neoplastic agent, or any other investigational anti-cancer agent within 2 weeks prior to Cycle 1, Day 1

• Completion of autologous stem cell transplant within 100 days prior to Cycle 1, Day 1

• Prior allogeneic stem cell transplant

• Current or history of CNS lymphoma

• Current Grade greater than (>) 1 toxicity (except alopecia and anorexia) from prior therapy

• Current Grade >1 peripheral neuropathy from any cause

• Glycosylated hemoglobin (HbA1c) >=7.5 percent (%)

• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)

• Prior irradiation to lung fields

• Clinically significant pulmonary disease

• Recent major surgery within 4 weeks prior to Cycle 1, Day 1, other than superficial lymph node biopsies for diagnosis

• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis

• Presence of positive test results for hepatitis B (hepatitis B surface antigen [HbsAg] and/or total hepatitis B core antibody [anti-HBc]) or hepatitis C (hepatitis C virus [HCV] antibody)

• Known history of human immunodeficiency virus (HIV) seropositive status

• Women who are pregnant or lactating or intending to become pregnant during the study

• Any abnormal laboratory values as specified in protocol

• Requirement for any excluded medication as specified in protocol

• History of other malignancy that could affect compliance with the protocol or interpretation of results

• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications, including inadequately controlled diabetes or significant cardiovascular disease

• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1, Day 1

• Participants in Phase 1b Stage Only: Vaccination with live vaccines within 6 months before Cycle 1, Day 1

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• DCDS0780A
Participants will receive escalating doses of DCDS0780A as intravenous infusion.
• Rituximab
Participants will receive rituximab at a dose of 375 mg/m^2 of body surface area as intravenous infusion.
• Obinutuzumab
Participants will receive obinutuzumab at a dose of 1000 milligrams (mg) as intravenous infusion.

Locations

Country	Name	City	State
United States	Medical Center of Aurora; Rocky Mountain Cancer Centers	Aurora	Colorado
United States	City of Hope National Medical Center	Duarte	California
United States	Willamette Valley Cancer Ctr - 520 Country Club	Eugene	Oregon
United States	New York University Cancer Cen	New York	New York
United States	Florida Cancer Specialists - Sarasota (North Catttlemen Rd)	Sarasota	Florida
United States	Stanford Cancer Center	Stanford	California
United States	Georgetown University Medical Center Lombardi Cancer Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events		Baseline up to 30 days after the last dose of study drug (up to 1 year)
Primary	Percentage of Participants with Dose-Limiting Toxicities		Days 1 to 21
Primary	Maximum Tolerated Dose (MTD) of DCDS0780A		Days 1 to 21
Primary	Recommended Phase 2 Dose (RP2D) of DCDS0780A		Days 1 to 21
Secondary	Area Under the Serum Concentration-Time Curve (AUC) for DCDS0780A Total Antibody	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to end of treatment (ET) visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Maximum Observed Serum Concentration (Cmax) for DCDS0780A Total Antibody	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Total Clearance (CL) of DCDS0780A Total Antibody	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Half-life (t1/2) of DCDS0780A Total Antibody	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Volume of Distribution Under Steady-State Conditions (Vss) of DCDS0780A Total Antibody	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Area Under the Plasma Concentration-Time Curve (AUC) for DCDS0780A Conjugate (Antibody-Conjugated Monomethyl Auristatin E [acMMAE])	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Maximum Observed Plasma Concentration (Cmax) for acMMAE	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Total Clearance (CL) of acMMAE	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Half-life (t1/2) of acMMAE	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Volume of Distribution Under Steady-State Conditions (Vss) of acMMAE	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Area Under the Plasma Concentration-Time Curve (AUC) for Unconjugated Monomethyl Auristatin E (MMAE)	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Maximum Observed Plasma Concentration (Cmax) for Unconjugated MMAE	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Total Clearance (CL) of Unconjugated MMAE	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Half-life (t1/2) of Unconjugated MMAE	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Volume of Distribution Under Steady-State Conditions (Vss) of Unconjugated MMAE	Monotherapy arm: Pre-infusion, 0.5, 4, hours after end of infusion on Cycle 1 Day 1; at Cycle 1 Days 2, 4 (or 5), 8, 11 (or 12), 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 2-4 Day 1, Cycle 2-4 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2 and 4 months after ET.; Combination therapy arm: Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 2; at Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 2, Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, Cycle 12, and every 4th cycle thereafter up to ET visit.; Pre-infusion = 0-4 hours before infusion; infusion duration = 90 minutes for first infusion and 30 minutes for other infusions, ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Obinutuzumab Serum Concentration	Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 1; Cycle 1 Days 4 (or 5); Pre-infusion and 0.5 hours after end of infusion on Cycle 1 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 1; Pre-infusion and 0.5 hours after end of infusion on Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2, 4, 6 months after ET.; Pre-infusion = 0-4 hours before infusion; infusion rate = 50 milligrams per hour initially (to be adjusted in case of reactions), ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Rituximab Serum Concentration	Pre-infusion, 0.5 hours after end of infusion on Cycle 1 Day 1; Cycle 1 Days 4 (or 5), 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycle 2 Day 1; Pre-infusion and 0.5 hours after end of infusion on Cycles 3-4 Day 1; Cycles 3-4 Days 8, 15; Pre-infusion and 0.5 hours after end of infusion on Cycles 5-8, 12, and every 4th cycle thereafter up to ET visit; 2, 4, 6 months after ET.; Pre-infusion = 0-4 hours before infusion; infusion rate = 50 milligrams per hour initially (to be adjusted in case of reactions), ET = 30 days after last dose (up to 1 year), cycle length = 21 days.	Pre-infusion on Cycle 1 Day 1 up to 1 year (detailed timeframe is provided in outcome description section)
Secondary	Percentage of Participants with Anti-DCDS0780A Antibodies		Baseline up to 2 to 4 months after last dose (up to 16 months)
Secondary	Absolute Lymphocyte Count		Cycle 1 Day 1 (Baseline); Day 1 of Cycles 4, 8, and every 4 cycles thereafter up to ET visit (up to 1 year); follow-up (up to 3.4 years)
Secondary	Change from Baseline in Intra-Patient Absolute Lymphocyte Counts		Cycle 1 Day 1 (Baseline); Day 1 of Cycles 4, 8, and every 4 cycles thereafter up to ET visit (up to 1 year); follow-up (up to 3.4 years)
Secondary	Time to CD19+ B-Cell Count Recovery to Baseline Value		Cycle 1 Day 1 (Baseline); Day 1 of Cycles 4, 8, and every 4 cycles thereafter up to ET visit (up to 1 year); follow-up (up to 3.4 years)
Secondary	Percentage of Participants with Best Overall Response of Complete Response (CR) or Partial Response (PR) Assessed According to Lugano Classification		Baseline up to first occurrence of disease progression or death from any cause within 30 days after the last dose of study drug (up to 1 year)
Secondary	Duration of Response Assessed According to Lugano Classification		From the first occurrence of a documented objective response (CR or PR) to the time of relapse or death from any cause (up to 1 year)
Secondary	Progression-Free Survival (PFS) Assessed According to Lugano Classification		Baseline up to first occurrence of disease progression or death from any cause within 30 days after the last dose of study drug (up to 1 year)
Secondary	Relative Dose Intensity (DI) Calculated as Ratio of Amount of Drug Actually Administered to the Amount Planned		Baseline up to 1 year