A Study Evaluating the Safety of Tocilizumab in Addition to Standard of Care Premedication Given Before Obinutuzumab + Chlorambucil in Participants With Untreated B-Cell Chronic Lymphocytic Leukemia (B-CLL) and Comorbidities

NCT02336048 | Terminated Phase 1

• 2 other identifiers: BO294482014-004594-16
• Study Type: interventional
• Target: 38
• Locations: 5 countries
• Sites: 14

Brief Summary

This multicenter, double-blind, randomized, placebo-controlled study will evaluate the safety of a single infusion of tocilizumab versus placebo, administered in addition to standard premedications (antipyretic, antihistamine, and corticosteroid) prior to the first infusion of obinutuzumab administered in combination with oral chlorambucil to participants with previously untreated B-CLL who have comorbidities. All eligible participants will be treated with a total of 6 cycles of obinutuzumab + chlorambucil (cycle length = 28 days).

Conditions

B-Cell Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Baseline up to approximately 196 days

Secondary Outcomes (24)

• Percentage of Participants With Infusion-Related Reactions (IRRs) as Assessed by Investigator and Reviewed by Endpoint Adjudication Committee (EAC)

  Day 1 (within 24 hours of first obinutuzumab infusion)

• Percentage of Participants With IRRs by Severity According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0)

  Day 1 (within 24 hours of first obinutuzumab infusion)

• Percentage of Participants With IRRS >= Grade 3 as assessed by the Investigator and Reviewed by the EAC

  Day 1 (within 24 hours of first obinutuzumab infusion)

• Number of Interruptions or Administration rate modifications of the First Infusion of Obinutuzumab

  Day 1 (within 24 hours of first obinutuzumab infusion)

• Percentage of Treatment Discontinuations due to IRR

  Day 1 (within 24 hours of first obinutuzumab infusion)

Study Arms (2)

Placebo + Obinutuzumab + Chlorambucil

ACTIVE COMPARATOR

Participants will receive placebo and standard premedications on Days 1 and 2 of Cycle 1 (cycle length= 28 days) along with obinutuzumab and chlorambucil administered for 6 cycles.

Drug: Chlorambucil; Drug: Obinutuzumab; Drug: Placebo; Other: Standard Premedication

Tocilizumab + Obinutuzumab + Chlorambucil

EXPERIMENTAL

Participants will receive tocilizumab and standard premedications on Days 1 and 2 of Cycle 1 (cycle length= 28 days) along with obinutuzumab and chlorambucil administered for 6 cycles.

Drug: Chlorambucil; Drug: Obinutuzumab; Other: Standard Premedication; Drug: Tocilizumab

Interventions

Chlorambucil DRUG

Chlorambucil at a dose of 0.5 milligrams per kilogram (mg/kg) will be administered orally per local prescribing information, on Days 1 and 15 of Cycles 1 to 6.

Placebo + Obinutuzumab + Chlorambucil; Tocilizumab + Obinutuzumab + Chlorambucil

Obinutuzumab DRUG

Obinutuzumab at a dose of 100 milligrams (mg) as an intravenous (IV) infusion will be administered on Cycle 1 Day 1; 900 mg as IV infusion on Cycle 1 Day 2; 1000 mg as IV infusion on Cycle 1 Days 8 and 15; and 1000 mg as IV infusion on Day 1 of each subsequent cycle for up to 6 cycles.

Also known as: RO5072759, GA101, Gazya, Gazyvaro

Placebo + Obinutuzumab + Chlorambucil; Tocilizumab + Obinutuzumab + Chlorambucil

Placebo DRUG

Placebo matching to tocilizumab will be administered as IV infusion on Cycle 1 Day 1 (prior to the first dose of obinutuzumab).

Placebo + Obinutuzumab + Chlorambucil

Standard Premedication OTHER

Standard-of-care premedication consisting of antipyretic, antihistamine, and corticosteroid will be administered as per United States Package Insert/ Summary of Product Characteristics on Cycle 1 Days 1 and 2 (prior to the first and second dose of obinutuzumab, respectively).

Placebo + Obinutuzumab + Chlorambucil; Tocilizumab + Obinutuzumab + Chlorambucil

Tocilizumab DRUG

Tocilizumab at a dose of 8 mg/kg or adjusted dose (up to a maximum threshold of 20 mg/kg) will be administered as IV infusion on Cycle 1 Day 1 (prior to the first dose of obinutuzumab).

Also known as: RO4877533, RoActemra, Actemra

Tocilizumab + Obinutuzumab + Chlorambucil

Eligibility Criteria

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

You may qualify if:

• Documented cluster of differentiation (CD) 20+ B-CLL according to NCI/IWCLL guideline
• Total Cumulative Illness Rating Scale (CIRS) score greater than (\>) 6 and/or creatinine clearance less than (\<) 70 milliliters per minute (mL/min)
• Previously untreated chronic lymphocytic leukemia (CLL) requiring treatment according to NCI/IWCLL guidelines who warrant treatment if they have any of the protocol-specified comorbidities
• Life expectancy \> 6 months
• Adequate hematological function, unless abnormalities are caused by underlying CLL
• Agreement to use highly effective contraceptive measures per protocol

You may not qualify if:

• Any previous CLL treatment
• Documented transformation of CLL to aggressive non-Hodgkin's lymphoma (Richter's transformation)
• Abnormal laboratory test values, unless abnormalities are caused by underlying CLL
• History of progressive multifocal leukoencephalopathy
• Previous treatment with tocilizumab for any indication
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
• Known hypersensitivity to any of the study drugs
• History of prior malignancy unless the malignancy has been treated with a curative intent or is in remission without treatment for at least (\>/=) 5 years prior to enrollment and with the exception of curatively-treated basal squamous cell carcinoma of the skin, low grade in situ carcinoma of the cervix, or low grade early stage localized prostate cancer treated surgically with curative intent and or ductal carcinoma in situ of the breast treated with lumpectomy alone
• Treatment with glucocorticoids at any dose (except topical formulations) during the 2 weeks prior to the start of Cycle 1 Day 1. Regular treatment with glucocorticoids (\> 5 days duration) is also prohibited during the 4-week screening period
• Ongoing treatment with immunosuppressive medications or anti-tumor necrosis factor biologic therapies
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with this protocol or interpretation of results, including significant cardiovascular or pulmonary disease
• Known active or history of recurrent bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) requiring treatment with intravenous (IV) antibiotics or hospitalization within 4 weeks prior to the start of Cycle 1 Day 1
• Active tuberculosis (TB) requiring treatment within 3 years prior to baseline or latent TB diagnosed during screening that has not been appropriately treated
• Vaccination with live or attenuated vaccines within 28 days prior to start of treatment
• Major surgery (within 4 weeks prior to Cycle 1 Day 1), other than for diagnosis

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (14)

Carmel medical center

Haifa, 3436212, Israel

Location

Meir Medical Center; Heamatology Dept

Kfar Saba, 4428164, Israel

Location

Kaplan Medical Center; Hematology Institute; Hematolgy Institute

Rehovot, 7610001, Israel

Location

Ziv Medical Center

Zfat, 1311001, Israel

Location

A.O. Universitaria S. Martino Di Genova; Ematologia 1

Genoa, Liguria, 16132, Italy

Location

Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

Milan, Lombardy, 20162, Italy

Location

Ospedale Businco; Ematologia

Cagliari, Sardinia, 09121, Italy

Location

Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica

Sant'Andrea Delle Fratte (PG), Umbria, 06132, Italy

Location

RECUH, Oncology Centre of Latvia; Clinic of Chemotherapy and Heamatology

Riga, 1079, Latvia

Location

Hospital Universitari Vall d'Hebron; Servicio de Hematologia

Barcelona, 08035, Spain

Location

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

Barcelona, 08036, Spain

Location

Hospital Univ. 12 de Octubre; Servicio de Hematologia

Madrid, 28041, Spain

Location

Hospital Universitario Virgen del Rocio; Servicio de Hematologia

Seville, 41013, Spain

Location

Barts & London School of Med; Medical Oncology

London, EC1A 7BE, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Chlorambucil; obinutuzumab; tocilizumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2015
• First Posted: January 12, 2015
• Study Start: June 26, 2015
• Primary Completion: September 21, 2018
• Study Completion: September 21, 2018
• Last Updated: April 8, 2021

Record last verified: 2021-04

Locations

LA (1); IT (4); ES (4); GB (1); IL (4)