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)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT02600897

Collaborator

(none)

114

Enrollment

Locations

Arms

68.8

Actual Duration (Months)

4.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma	Drug: Lenalidomide Drug: Obinutuzumab Drug: Polatuzumab Vedotin Drug: Rituximab	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

114 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 23, 2016

Actual Primary Completion Date :

Dec 15, 2021

Actual Study Completion Date :

Dec 15, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose-escalation Cohort: FL 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 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. Drug: Obinutuzumab 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. Drug: Polatuzumab Vedotin 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.
Experimental: Dose-escalation Cohort: DLBCL 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 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. Drug: Polatuzumab Vedotin 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. Drug: Rituximab 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.
Experimental: Expansion Cohort: FL 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 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. Drug: Obinutuzumab 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.
Experimental: Expansion Cohort: DLBCL 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 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. Drug: Rituximab 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.

Outcome Measures

Primary Outcome Measures

Percentage of Participants with CR, Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans [Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)]
Percentage of Participants with Adverse Events (AEs) [Up to approximately 3 years]
Percentage of Participants with Dose-Limiting Toxicities (DLTs) [Up to approximately 3 years]

Secondary Outcome Measures

Percentage of participants with CR, determined by the investigator on the basis of PET and CT scans [Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)]
Percentage of Participants with CR, Determined by the Independent Review Committee (IRC) and Investigator on the Basis of CT Scans Alone [Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)]
Percentage of Participants with Objective Response, Determined by the IRC and Investigator on the Basis of PET and CT Scans [Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)]
Percentage of Participants with Objective Response, Determined by the IRC and Investigator on the Basis of CT Scans Alone [Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)]
Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of CT Scans Alone [Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)]
Percentage of Participants With Best Response of Clinical Response (CR) or Partial Response (PR), Determined by the Investigator on the Basis of CT Scans Alone [Up to approximately 3 years]
Observed Serum Obinutuzumab Concentration [Pre-dose and/or 30 minutes post-dose on Day 1 of Cycles 1, 2, 4, and 6 during induction; pre-dose on Day 1 of Months 1, 7, 13, and/or 19 during the post-induction phase; then up to 2 years after last dose as available (maximum 5 years)]
Observed Serum Rituximab Concentration [Pre-dose and/or 30 minutes post-dose on Day 1 of Cycles 1, 2, 4, and 6 during induction; pre-dose on Day 1 of Months 1, 7, 13, and/or 19 during the post-induction phase; then up to 2 years after last dose as available (maximum 5 years)]
Observed Serum and Plasma Polatuzumab Vedotin Concentration [Pre-dose and/or 30 minutes post-dose on Days 1, 8, and 15 of Cycle 1; pre-dose and/or 30 minutes post-dose on Day 1 of Cycles 2, 4, and 6 during induction; then up to 2 years after last dose as available (maximum 5 years)]
Observed Plasma Lenalidomide Concentration [Pre-dose and/or 0.5, 1, 2, 4, and 8 hours post-dose on Days 1 and 15 of Cycle 1 and on Day 1 of Cycle 6 (maximum 5 years)]
Percentage of Participants with Human Anti-human Antibodies (HAHAs) to Obinutuzumab [Pre-dose on Day 1 of Cycles 1 and 6 during induction; then up to 2 years after last dose as available (maximum 5 years)]
Percentage of Participants with Human Anti-chimeric Antibodies (HACAs) to Rituximab [Pre-dose on Day 1 of Cycles 1 and 6 during induction; then up to 2 years after last dose as available (maximum 5 years)]
Percentage of Participants with Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin [Pre-dose on Day 1 of Cycles 1, 2, and 4 during induction; then up to 2 years after last dose as available (maximum 5 years)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital	Marietta	Georgia	United States	30060
2	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
3	University of Missouri/Ellis Fischel	Columbia	Missouri	United States	65212
4	Washington University; Wash Uni. Sch. Of Med	Saint Louis	Missouri	United States	63110
5	NYU School of Medicine	New York	New York	United States	10016
6	Rocky Mountain Cancer Centers, LLP	Irving	Texas	United States	75063
7	Texas Oncology-Tyler	Irving	Texas	United States	75063
8	Texas Oncology San Antonio Medical Center	San Antonio	Texas	United States	78240
9	Insititut Catala D'Oncologia	Hospitalet de Llobregat	Barcelona	Spain	08908
10	Hospital Clínico Málaga	Málaga	Malaga	Spain	29010
11	Complejo Hospitalario de Navarra	Pamplona	Navarra	Spain	31008
12	Clínica Universidad de Navarra	Pamplona	Navarra	Spain	31620
13	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
14	Hospital Clínic. Barcelona	Barcelona		Spain	08036
15	Hospital Santa Creu i Sant Pau	Barcelona		Spain	08041
16	Hospital Gregorio Marañon	Madrid		Spain	28007
17	H. Universitario Leonor	Madrid		Spain	28031
18	Hospital Universitario Fundacion Jimenez Diaz.	Madrid		Spain	28040
19	Hospital La Fe	Valencia		Spain
20	St James University Hospital	Leeds		United Kingdom	LS9 7TF
21	University Hospitals of Leicester NHS Trust - Leicester Royal Infirmary	Leicester		United Kingdom	LE1 5WW
22	Royal Liverpool University Hospital	Liverpool		United Kingdom	L7 8XP
23	Barts Hospital; Institute of Cancer	London		United Kingdom	EC1M 6BQ
24	Sarah Cannon Research Institute	London		United Kingdom	W1G 6AD
25	Maidstone & Tonbridge Wells Hospital; Kent Oncology Center	Maidstone		United Kingdom	ME16 9QQ
26	Nottingham University Hospitals NHS Trust - City Hospital	Nottingham		United Kingdom	NG5 1PB
27	Barking, Havering and Redbridge University Hospitals NHS Trust - Queen's Hospital	Romford		United Kingdom	RM7 0AG
28	The Royal Wolverhampton Hospitals NHS Trust; Department of Haematology	Wolverhampton		United Kingdom	WV10 0QP