Clinical trial NCT02600897: A Study of Obinutuzumab, Polatuzumab Vedotin, and Lenalidomide in Relapsed or Refractory Follicular Lymphoma (FL) and Rituximab in Combination With Polatuzumab Vedotin and Lenalidomide in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Official title: A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Polatuzumab Vedotin and Lenalidomide in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Polatuzumab Vedotin and Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-11-09
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment with obinutuzumab, polatuzumab vedotin, and lenalidomide in participants with relapsed or refractory (R/R) follicular lymphoma (FL) and rituximab in combination with polatuzumab vedotin and lenalidomide in participants with R/R diffuse large B-cell lymphoma (DLBCL), followed by post-induction treatment with obinutuzumab in combination with lenalidomide in participants with FL who achieve a complete response (CR), partial response (PR), or stable disease (SD) at end of induction (EOI) and post-induction treatment with rituximab plus lenalidomide in participants with DLBCL who achieve a CR or PR at EOI.


Eligibility criteria: Inclusion Criteria:

* Age greater than or equal to (\>/=) 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* For obinutuzumab in combination with polatuzumab vedotin and lenalidomide (G + Pola + Len) treatment group: R/R FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
* For rituximab in combination with polatuzumab vedotin and lenalidomide (R + Pola + Len) treatment group: R/R DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody in patients who are not eligible for autologous stem-cell transplantation or who have experienced disease progression following treatment with high-dose chemotherapy plus autologous stem-cell transplantation
* Histologically documented CD20-positive B-cell lymphoma as determined by the local laboratory
* fluorodeoxyglucose (FDG)-avid lymphoma (i.e., positron emission tomography (PET)-positive lymphoma)
* At least one bi-dimensionally measurable lesion
* Agreement to remain abstinent or use adequate contraception, among women or men of childbearing potential

Exclusion Criteria:

* Grade 3b follicular lymphoma
* History of transformation of indolent disease to diffuse large B-cell lymphoma (DLBCL)
* Known CD20-negative status at relapse or progression
* Central nervous system (CNS) lymphoma or leptomeningeal infiltration
* Prior allogeneic stem-cell transplantation (SCT), or autologous SCT within 100 days prior to Day 1 of Cycle 1
* Current use of systemic immunosuppressant(s), or prior anti-cancer therapy to include: lenalidomide, fludarabine, or alemtuzumab within 12 months; radioimmunoconjugate within 12 weeks; mAb or antibody-drug conjugate within 4 weeks; or radiotherapy/chemotherapy/hormone therapy/targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1
* Active infection
* Positive for human immunodeficiency virus (HIV) or hepatitis B or C
* Receipt of a live virus vaccine within 28 days prior to Day 1 of Cycle 1
* Poor hematologic, renal, or hepatic function
* Pregnant or lactating women
* Life expectancy less than (\<) 3 months

Primary outcomes:
measure: Percentage of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle = 28 days) in dose-escalation phase
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: From study start up to end of study (Up to a maximum of 69 months)
measure: Percentage of Participants With Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Secondary outcomes:
measure: Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
measure: Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
measure: Percentage of Participants With CR at EOI, Determined by Investigator on the Basis of CT Scans Alone
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
measure: Percentage of Participants With Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (cycle=28 days) (up to approximately 28 weeks)
measure: Percentage of Participants With Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
measure: Percentage of Participants With Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
measure: Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of CT Scans Alone
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
measure: Percentage of Participants With Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone
timeFrame: Up to every 6 months until disease progression, unacceptable toxicity or study completion (up to approximately 69 months)
measure: Observed Serum Obinutuzumab Concentration
timeFrame: Day 1 of Cycles 1, 2, 4 & 6: predose & 30 mins postdose; EOI: predose; Day 1 of Maintenance Months 1,7, 13, 19;Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
measure: Observed Serum Rituximab Concentration
timeFrame: Day 1 of Cycles 1, 2, 4, 6: predose and 30 mins post-dose (1 cycle = 28 days) (up to approximately 69 months)
measure: Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody
timeFrame: Day 1 of Cycles 1, 2, 4: predose (1 cycle = 28 days), Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
measure: Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE)
timeFrame: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1; Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
measure: Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
timeFrame: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1 and Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
measure: Observed Plasma Lenalidomide Concentration
timeFrame: Day 1 Cycle 1: predose and 2 hours (hr) post-dose; Day 15 Cycle 1: predose, 0.5hr, 1hr, 2hr, 4hr, 8hr post-dose; Day 1 Cycle 6: 2hr post-dose; unscheduled visits: 2hr post-dose (1 cycle = 28 days) (up to approximately 69 months)
measure: Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab
timeFrame: Baseline up to approximately 2 years after last dose (up to approximately 69 months)
measure: Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab
timeFrame: Baseline up to approximately 2 years after last dose (up to approximately 69 months)
measure: Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin
timeFrame: Baseline up to approx. 2 years after the last dose of polatuzumab vedotin (up to approximately 30 months)
Other outcomes:
Locations:
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital
state: Georgia
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Columbia
country: United States
facility: University of Missouri/Ellis Fischel
state: Missouri
city: Saint Louis
country: United States
facility: Washington University; Wash Uni. Sch. Of Med
state: Missouri
city: New York
country: United States
facility: NYU School of Medicine
state: New York
city: Irving
country: United States
facility: Rocky Mountain Cancer Centers, LLP
state: Texas
city: Irving
country: United States
facility: Texas Oncology-Tyler
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology San Antonio Medical Center
state: Texas
city: Hospitalet de Llobregat
country: Spain
facility: Insititut Catala D'Oncologia
state: Barcelona
city: Málaga
country: Spain
facility: Hospital Clínico Málaga
state: Malaga
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic. Barcelona
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Madrid
country: Spain
facility: H. Universitario Leonor
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz.
city: Valencia
country: Spain
facility: Hospital La Fe
city: Leeds
country: United Kingdom
facility: St James University Hospital
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust - Leicester Royal Infirmary
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: Barts Hospital; Institute of Cancer
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: Maidstone
country: United Kingdom
facility: Maidstone & Tonbridge Wells Hospital; Kent Oncology Center
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust - City Hospital
city: Romford
country: United Kingdom
facility: Barking, Havering and Redbridge University Hospitals NHS Trust - Queen's Hospital
city: Wolverhampton
country: United Kingdom
facility: The Royal Wolverhampton Hospitals NHS Trust; Department of Haematology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Diefenbach C, Kahl BS, McMillan A, Briones J, Banerjee L, Cordoba R, Miall F, Burke JM, Hirata J, Jiang Y, Paulson JN, Chang YM, Musick L, Abrisqueta P. Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Lancet Haematol. 2021 Dec;8(12):e891-e901. doi: 10.1016/S2352-3026(21)00311-2.