A Study of Atezolizumab in Combination With an Immunotherapy Agent Investigated With or Without Anti-Cd20 Therapy in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

NCT03369964 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: GO401502017-002587-41
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This study will investigate the safety, pharmacology, and activity of atezolizumab in combination with immunotherapy agents with or without an anti-CD20 agent (i.e., obinutuzumab) in patients with relapsed or refractory (R/R) follicular lymphoma (FL). The first immunotherapy molecule investigated will be emactuzumab (Arm A) in two combinations.

Conditions

Lymphoma, Non-Hodgkin

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants with Adverse Events

  Baseline to end of study (approximately 48 months)

Secondary Outcomes (7)

• Serum concentration of Atezolizumab at specified timepoints

  Cohort A1 and A3 Cycle 2-4, Day 1 pre and post infusion; Cycle 6, 8, Day 1 pre-infusion; Every 8 cycles after cycle 8, Day 1 pre-infusion. Cohort A2 and A4 Cycle 2 and 4, Day 1 pre- and post infusion, Cycle 3,6, and 8, Day 1 pre-infusion.

• Serum concentration of Obinutuzumab at specified timepoints

  Cohort A2 and A4 Cycle 1,6,8, and every 8 cycles post cycle 8, Day 1 prior to infusion; Cycle 1, Day 2, post infusion; Cycle 1, Day 8 and 15, pre and post infusion; Cycle 2,3, and 4, Day 1, pre and post infusion. (Cycle = 21 days)

• Serum concentration of Emactuzumab at specified timepoints

  Cohort A1 and A3 Cycle 1-4, Day 1 pre and post infusion; Cycle 6, 8 and every 8 cycles post cycle 8, pre-infusion. Cycle 1-4 Day 1 pre and post infusion; Cycle 1, Day 15 pre-infusion. Cycle 6, 8 and every 8 cycles post cycle 8, Day 1 pre-infusion.

• Objective Response

  Baseline to end of study (approximately 48 months)

• Duration of Objective Response (DOR)

  Baseline to end of study (approximately 48 months)

Study Arms (2)

Atezolizumab + Emactuzumab

EXPERIMENTAL

Participants will receive Atezolizumab and Emactuzumab on Day 1 of each 21- day cycle

Drug: Atezolizumab; Drug: Emactuzumab

Atezolizumab + Emactuzumab + Obinutuzumab

ACTIVE COMPARATOR

Participants will receive Atezolizumab, Emactuzumab, and Obinutuzumab on Day 1 of each- 21 day cycle (starting in cycle 2) (Atezolizumab starting in cycle 2); and Obinutuzumab on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2-8.

Drug: Atezolizumab; Drug: Emactuzumab; Drug: Obinutuzumab

Interventions

Atezolizumab DRUG

In Cohort A1, Atezolizumab will be administered, 1200 mg IV, every 3 weeks starting on Cycle 2; Day 1 of a 21 day cycle In Cohort A2, Atezolizumab will be administered, 1200 mg IV, starting on Cycle 2; Day 1 of a 21 day cycle In Cohort A2 , In Cycle 2-8, Atezolizumab will be administered, 1200 mg IV on day 1 of each 21 day cycle In Cohort A2, Atezolizumab will be administered, 1200 mg IV starting on Cycle 9; Day 1 of each 21 day cycle

Atezolizumab + Emactuzumab; Atezolizumab + Emactuzumab + Obinutuzumab

Emactuzumab DRUG

In Cohort A1, Emactuzumab will be administered 1000 mg IV, every 3 weeks, starting on Cycle 1; Day 1 of a 21 day cycle. In Cohort A2, Emactuzumab will be administered 1000 mg IV, starting on Cycle 1 Day 1 of a 21 day cycle. In Cohort A2, in cycle 2-8, Emactuzumab will be administered 1000 mg IV, on day 1 of each 21 day cycle. In Cohort A2, Emactuzumab will be administered 1000 mg IV starting on Cycle 9; on Day 1 of each 21 day cycle

Atezolizumab + Emactuzumab; Atezolizumab + Emactuzumab + Obinutuzumab

Obinutuzumab DRUG

In Cohort A2, Obinutuzumab will be administered 1000 mg IV starting on Cycle 1; Day 1 of a 21 day cycle In Cohort A2, Obinutuzumab will be administered again on days 8 and 15 (Cycle 1) of a 21 day cycle In Cohort A2, in cycle 2-8, Obinutuzumab will be administered 1000 mg IV on day 1 of each 21 day cycle

Atezolizumab + Emactuzumab + Obinutuzumab

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• Life expectancy ≥ 12 weeks
• At least two bi-dimensionally measurable nodal lesions ≥ 1.5 centimeters (cm) in its longest diameter by imaging
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent
• For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm
• Consent to collection of a pre-treatment tumor sample, on-treatment biopsy, and, if applicable, a tumor tissue sample at the time of progressive disease (PD)
• \- Patients receiving therapeutic anticoagulation should be switched to low molecular weight heparin (LMWH) before the first cycle of obinutuzumab

You may not qualify if:

• Any approved systemic anti-cancer therapy (including chemotherapy) or hormonal therapy within 3 weeks prior to initiation of study treatment
• Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to enrollment
• Known central nervous system (CNS) lymphoma, leptomeningeal lymphoma
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Uncontrolled hypercalcemia
• History of other malignancy within 5 years prior to screening with the exception of malignancies with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
• Known hypersensitivity to any of the study drugs
• History of sensitivity to mannitol
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
• Pregnant and lactating women
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation, emactuzumab formulation, or obinutuzumab formulation
• History of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis (RA), inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
• Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (2)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

atezolizumab; emactuzumab; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: December 12, 2017
• Study Start: March 14, 2018
• Primary Completion: December 31, 2018
• Study Completion: August 31, 2019
• Last Updated: April 5, 2018

Record last verified: 2018-04

Locations

US (2)