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)

NCT02600897 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: GO298342015-001999-22
• Study Type: interventional
• Target: 114
• Locations: 3 countries
• Sites: 28

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.

Conditions

Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With Dose-Limiting Toxicities (DLTs)

  A DLT was defined as any one of the following toxicities occurring during the first cycle of treatment and assessed by the investigator as related to study treatment: Any adverse event of any grade that lead to a delay of \> 14 days in the start of the next treatment cycle, Grade 3 or 4 non-hematologic adverse events with few exceptions; increase in hepatic transaminase \> 3 x baseline and an increase in direct bilirubin \> 2 x upper limits of normal (ULN), without any findings of cholestasis or jaundice, or signs of hepatic dysfunction, and in the absence of other contributory factors; hematologic adverse events that met a few protocol specified criteria. DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0). Percentages have been rounded off to the first decimal point.

  Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle = 28 days) in dose-escalation phase

• Percentage of Participants With Adverse Events (AEs)

  An AE 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 AE 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. Percentages have been rounded off to the first decimal point.

  From study start up to end of study (Up to a maximum of 69 months)

• 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

  CR at EOI was assessed by IRC according to Modified Lugano Response Criteria (MLRC). Per MLRC, CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites (ELS) with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS) where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake \> mediastinum but ≤ liver; 4=uptake moderately \> liver; 5=uptake markedly higher than liver and/or new lesions no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, immunohistochemistry (IHC) negative. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.

  6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)

Secondary Outcomes (17)

• Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans

  6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)

• Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone

  6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)

• Percentage of Participants With CR at EOI, Determined by Investigator on the Basis of CT Scans Alone

  6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)

• Percentage of Participants With Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans

  6 to 8 weeks after Day 1 of Cycle 6 (cycle=28 days) (up to approximately 28 weeks)

• Percentage of Participants With Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans

  6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)

Study Arms (4)

Dose-escalation Cohort: FL

EXPERIMENTAL

Participants with R/R FL will receive 6 months of induction treatment with polatuzumab vedotin and lenalidomide at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and lenalidomide when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 24-month maintenance regimen consisting of lenalidomide and obinutuzumab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle).

Drug: Lenalidomide; Drug: Obinutuzumab; Drug: Polatuzumab Vedotin

Dose-escalation Cohort: DLBCL

EXPERIMENTAL

Participants with R/R DLBCL will receive 6 months of induction treatment with fixed dose of polatuzumab vedotin and rituximab along with dose escalating lenalidomide. Lenalidomide will be administered at escalating doses to identify the recommended Phase 2 dose (RP2D) for lenalidomide. Those who achieve CR and PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 6-month consolidation regimen consisting of lenalidomide and rituximab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle).

Drug: Lenalidomide; Drug: Polatuzumab Vedotin; Drug: Rituximab

Expansion Cohort: FL

EXPERIMENTAL

Participants with R/R FL who received induction treatment with polatuzumab vedotin and lenalidomide, in addition to obinutuzumab and achieved CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will receive a 24-months maintenance regimen consisting of lenalidomide and obinutuzumab for first 12 months followed by obinutuzumab treatment for next 12 months. Post-induction therapy will start 8 weeks after Cycle 6 Day 1.

Drug: Lenalidomide; Drug: Obinutuzumab

Expansion Cohort: DLBCL

EXPERIMENTAL

Participants with R/R DLBCL who received induction treatment with polatuzumab vedotin and lenalidomide in addition to rituximab and achieved CR or PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will receive a 6-month consolidation regimen consisting of lenalidomide and rituximab. Post-induction therapy will start 8 weeks after Cycle 6 Day 1.

Drug: Lenalidomide; Drug: Rituximab

Interventions

Lenalidomide DRUG

All participants will receive lenalidomide oral capsules at doses of 10, 15, or 20 milligrams (mg) on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by post-induction treatment at a dose of 10 mg once daily on Days 1 to 21 of each subsequent 28-day cycle. Post-induction lenalidomide may continue for up to 12 months until disease progression or unacceptable toxicity for participants with R/R FL and up to 6 months until disease progression or unacceptable toxicity for participants with R/R DLBCL.

Dose-escalation Cohort: DLBCL; Dose-escalation Cohort: FL; Expansion Cohort: DLBCL; Expansion Cohort: FL

Obinutuzumab DRUG

Participants will receive a fixed dose of obinutuzumab, 1000 mg via intravenous (IV) infusion to be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 followed by post-induction treatment at a dose of 1000 mg via IV infusion on Day 1 of every other month for up to 24 months until disease progression or unacceptable toxicity.

Dose-escalation Cohort: FL; Expansion Cohort: FL

Polatuzumab Vedotin DRUG

Participants with R/R FL will receive polatuzumab vedotin via IV infusion at doses of 1.4 or 1.8 milligrams per kilogram (mg/kg) on Day 1 of each 28-day cycle for up to 6 months during induction treatment. Participants wit R/R DLBCL will receive polatuzumab vedotin via IV infusion at dose 1.8 mg/kg on Day 1 of each 28-day cycle for up to 6 months during induction treatment.

Dose-escalation Cohort: DLBCL; Dose-escalation Cohort: FL

Rituximab DRUG

Participants will receive a fixed dose of rituximab, 375 mg/m\^2 via intravenous (IV) infusion to be given on Days 1 of Cycle 1 to 6 followed by post-induction treatment at a dose of 375 mg/m\^2 via IV infusion on Day 1 of every other month for up to 6 months, until disease progression or unacceptable toxicity.

Dose-escalation Cohort: DLBCL; Expansion Cohort: DLBCL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (28)

Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital

Marietta, Georgia, 30060, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University of Missouri/Ellis Fischel

Columbia, Missouri, 65212, United States

Location

Washington University; Wash Uni. Sch. Of Med

St Louis, Missouri, 63110, United States

Location

NYU School of Medicine

New York, New York, 10016, United States

Location

Rocky Mountain Cancer Centers, LLP

Irving, Texas, 75063, United States

Location

Texas Oncology-Tyler

Irving, Texas, 75063, United States

Location

Texas Oncology San Antonio Medical Center

San Antonio, Texas, 78240, United States

Location

Insititut Catala D'Oncologia

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Clínico Málaga

Málaga, Malaga, 29010, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Clínica Universidad de Navarra

Pamplona, Navarre, 31620, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic. Barcelona

Barcelona, 08036, Spain

Location

Hospital Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Gregorio Marañon

Madrid, 28007, Spain

Location

H. Universitario Leonor

Madrid, 28031, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz.

Madrid, 28040, Spain

Location

Hospital La Fe

Valencia, Spain

Location

St James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

University Hospitals of Leicester NHS Trust - Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

Barts Hospital; Institute of Cancer

London, EC1M 6BQ, United Kingdom

Location

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

Maidstone & Tonbridge Wells Hospital; Kent Oncology Center

Maidstone, ME16 9QQ, United Kingdom

Location

Nottingham University Hospitals NHS Trust - City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Barking, Havering and Redbridge University Hospitals NHS Trust - Queen's Hospital

Romford, RM7 0AG, United Kingdom

Location

The Royal Wolverhampton Hospitals NHS Trust; Department of Haematology

Wolverhampton, WV10 0QP, United Kingdom

Location

Related Publications (2)

• Abrisqueta P, Gonzalez-Barca E, Panizo C, Perez JMA, Miall F, Bastos-Oreiro M, Triguero A, Banerjee L, McMillan A, Seymour E, Hirata J, de Guzman J, Sharma S, Jin HY, Musick L, Diefenbach C. Polatuzumab vedotin plus rituximab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Lancet Haematol. 2024 Feb;11(2):e136-e146. doi: 10.1016/S2352-3026(23)00345-9. Epub 2024 Jan 5.

  PMID: 38190832 DERIVED

• 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.

  PMID: 34826412 DERIVED

MeSH Terms

Conditions

Recurrence; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse

Interventions

Lenalidomide; obinutuzumab; polatuzumab vedotin; Rituximab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2015
• First Posted: November 9, 2015
• Study Start: March 24, 2016
• Primary Completion: December 15, 2021
• Study Completion: December 15, 2021
• Last Updated: December 26, 2023
• Results First Posted: December 26, 2023

Record last verified: 2023-12

Locations

GB (9); US (8); ES (11)