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

Phase 1TerminatedNCT02336048

Hoffmann-La Roche38 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

B-Cell Chronic Lymphocytic Leukemia

Interventions

Chlorambucil

ObinutuzumabDRUG

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.

Standard PremedicationOTHER

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).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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 * Positive test results for chronic hepatitis B infection or positivity for hepatitis B core antibody * Positive test results for hepatitis C * Known history of human immuno-deficiency virus (HIV) seropositive status * Positive test results for human T-lymphotropic virus 1 (HTLV 1) * Pregnant or lactating women * Participation in another clinical study with drug intervention unless the last dose administered was greater than 5 half-lives of the study product prior to study start * Any participant actively taking anti-platelet medication or any participant who is fully anticoagulated with warfarin, low-molecular weight heparin or a novel oral anticoagulant including dabigatran, rivaroxiban, epixiban, and similar * Previous treatment with B-cell depleting agents * Any inherited bleeding disorder

Locations (14)

Carmel medical center

Haifa, Israel

Meir Medical Center; Heamatology Dept

Kfar Saba, Israel

Kaplan Medical Center; Hematology Institute; Hematolgy Institute

Rehovot, Israel

Ziv Medical Center

Zfat, Israel

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

Genoa, Liguria, Italy

Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

Milan, Lombardy, Italy

Ospedale Businco; Ematologia

Cagliari, Sardinia, Italy

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

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

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

Riga, Latvia

Hospital Universitari Vall d'Hebron; Servicio de Hematologia

Barcelona, Spain

...and 4 more locations

Outcomes

Primary Outcomes

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

Time frame: Baseline up to approximately 196 days

Secondary Outcomes

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