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

NCT ID: NCT02336048

Last Updated: 2021-04-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-26
• Study Completion Date: 2018-09-21

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo + Obinutuzumab + Chlorambucil

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.

Group Type: ACTIVE_COMPARATOR

Chlorambucil

Intervention Type: 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.

Obinutuzumab

Intervention Type: 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.

Placebo

Intervention Type: DRUG

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

Standard Premedication

Intervention Type: 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).

Tocilizumab + Obinutuzumab + Chlorambucil

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.

Group Type: EXPERIMENTAL

Chlorambucil

Intervention Type: 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.

Obinutuzumab

Intervention Type: 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.

Standard Premedication

Intervention Type: 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).

Tocilizumab

Intervention Type: 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).

Interventions

Chlorambucil

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.

Intervention Type: DRUG

Obinutuzumab

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Standard Premedication

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).

Intervention Type: OTHER

Tocilizumab

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).

Intervention Type: DRUG

Other Intervention Names

RO5072759, GA101, Gazya, Gazyvaro; RO4877533, RoActemra, Actemra

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

Barcelona, , Spain

Hospital Univ. 12 de Octubre; Servicio de Hematologia

Madrid, , Spain

Hospital Universitario Virgen del Rocio; Servicio de Hematologia

Seville, , Spain

Barts & London School of Med; Medical Oncology

London, , United Kingdom

Countries

Israel; Italy; Latvia; Spain; United Kingdom

Other Identifiers

2014-004594-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO29448

Identifier Type: -

Identifier Source: org_study_id