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B-Cell Chronic Lymphocytic LeukemiaPhase 1NCT02336048

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

A Phase 1 study testing Chlorambucil, Obinutuzumab and Standard Premedication in people with B-Cell Chronic Lymphocytic Leukemia, run by Hoffmann-La Roche at 14 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
B-Cell Chronic Lymphocytic Leukemia
What is being tested?
Chlorambucil, Obinutuzumab and Standard Premedication
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
38 participants
Where
14 sitesin 5 countries
Study dates
26 Jun 2015to 21 Sep 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 24Show fewer
  • 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

Trial locations and contacts

14 sites in 5 countries.

14 sites in 5 countries

Israel4 sites

  • Carmel medical center

    Haifa, 3436212

  • Meir Medical Center; Heamatology Dept

    Kfar Saba, 4428164

  • Kaplan Medical Center; Hematology Institute; Hematolgy Institute

    Rehovot, 7610001

  • Ziv Medical Center

    Zfat, 1311001

Other trials in Israel

Italy4 sites

  • Ospedale Businco; Ematologia

    Cagliari, Sardinia, 09121

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

    Genoa, Liguria, 16132

  • Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

    Milan, Lombardy, 20162

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

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

Other trials in Italy

Spain4 sites

  • Hospital Universitari Vall d'Hebron; Servicio de Hematologia

    Barcelona, 08035

  • Hospital Clínic i Provincial; Servicio de Hematología y Oncología

    Barcelona, 08036

  • Hospital Univ. 12 de Octubre; Servicio de Hematologia

    Madrid, 28041

  • Hospital Universitario Virgen del Rocio; Servicio de Hematologia

    Seville, 41013

Other trials in Spain

Latvia1 site

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

    Riga, 1079

Other trials in Latvia

United Kingdom1 site

  • Barts & London School of Med; Medical Oncology

    London, EC1A 7BE

Other trials in United Kingdom

About this study

Official title: A Multicenter, Double-Blind, Randomized, and Placebo-controlled Phase Ib Study Evaluating the Safety of Adding Tocilizumab to Standard Premedications Prior to Administration of Obinutuzumab in Combination With Chlorambucil in Patients With Previously Untreated B-Cell Chronic Lymphocytic Leukemia and Comorbidities

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).

Being tested
Chlorambucil, Obinutuzumab, Placebo, Standard Premedication, Tocilizumab
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ChlorambucilDrug

    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.

  • ObinutuzumabDrug

    Also called RO5072759, GA101, Gazya, Gazyvaro

    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.

  • PlaceboDrug

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

  • 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).

  • TocilizumabDrug

    Also called RO4877533, RoActemra, Actemra

    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).

Study groups in NCT02336048
Study groupRoleWhat they receive
Placebo + Obinutuzumab + ChlorambucilActive comparatorParticipants 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.
Receives: Drug: Chlorambucil; Drug: Obinutuzumab; Drug: Placebo; Other: Standard Premedication
Tocilizumab + Obinutuzumab + ChlorambucilExperimentalParticipants 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.
Receives: Drug: Chlorambucil; Drug: Obinutuzumab; Other: Standard Premedication; Drug: Tocilizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Baseline up to approximately 196 days

Secondary outcomes (24)

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

    Measured: Day 1 (within 24 hours of first obinutuzumab infusion)

  2. 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)

    Measured: Day 1 (within 24 hours of first obinutuzumab infusion)

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

    Measured: Day 1 (within 24 hours of first obinutuzumab infusion)

  4. Number of Interruptions or Administration rate modifications of the First Infusion of Obinutuzumab

    Measured: Day 1 (within 24 hours of first obinutuzumab infusion)

  5. Percentage of Treatment Discontinuations due to IRR

    Measured: Day 1 (within 24 hours of first obinutuzumab infusion)

  6. Percentage of Participants With Overall Response as Assessed by Investigator According to NCI/ International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines

    Measured: 84 days after last treatment (up to approximately 280 days)

  7. Percentage of Participants With Negative Results for Minimal Residual Disease (MRD) Measured According to NCI/IWCLL Guidelines

    Measured: 84 days after last treatment (up to approximately 280 days)

  8. Area Under the Serum Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC[0-inf]) of Obinutuzumab

    Measured: Cycle 1 Day 1 (C1D1), C1D2: Pre-dose (0 hours [hrs]), immediately after obinutuzumab infusion (approximately 7 hrs); C1D8, C1D15, C2D1, C6D1: pre-dose (0 hrs); additionally at 3 months after last treatment (9 months) (1 cycle=28 days)

  9. Maximum Observed Serum Concentration (Cmax) of Obinutuzumab

    Measured: C1D1, C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D8, C1D15, C2D1, C6D1: pre-dose (0 hrs); additionally at 3 months after last treatment (9 months) (1 cycle=28 days)

  10. Terminal Half-Life (t1/2) of Obinutuzumab

    Measured: C1D1, C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D8, C1D15, C2D1, C6D1: pre-dose (0 hrs); additionally at 3 months after last treatment (9 months) (1 cycle=28 days)

  11. Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC[0-last]) of Obinutuzumab

    Measured: C1D1, C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D8, C1D15, C2D1, C6D1: pre-dose (0 hrs); additionally at 3 months after last treatment (9 months) (1 cycle=28 days)

  12. Total Clearance (CL) of Obinutuzumab

    Measured: C1D1, C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D8, C1D15, C2D1, C6D1: pre-dose (0 hrs); additionally at 3 months after last treatment (9 months) (1 cycle=28 days)

  13. Volume of Distribution (Vd) of Obinutuzumab

    Measured: C1D1, C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D8, C1D15, C2D1, C6D1: pre-dose (0 hrs); additionally at 3 months after last treatment (9 months) (1 cycle=28 days)

  14. AUC(0-inf) of Tocilizumab

    Measured: C1D1, C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D1: immediately after tocilizumab infusion (1 hr); C1D3; C1D8, C1D15, C2D1: pre-dose (0 hrs) (1 cycle=28 days)

  15. Cmax of Tocilizumab

    Measured: C1D1, C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D1: immediately after tocilizumab infusion (1 hr); C1D3; C1D8, C1D15, C2D1: pre-dose (0 hrs) (1 cycle=28 days)

  16. t1/2 of Tocilizumab

    Measured: C1D1, C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D1: immediately after tocilizumab infusion (1 hr); C1D3; C1D8, C1D15, C2D1: pre-dose (0 hrs) (1 cycle=28 days)

  17. AUC(0-last) of Tocilizumab

    Measured: C1D1, C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D1: immediately after tocilizumab infusion (1 hr); C1D3; C1D8, C1D15, C2D1: pre-dose (0 hrs) (1 cycle=28 days)

  18. Change From Baseline in Interleukin (IL)-6 Level

    1 cycle=28 days

    Measured: C1D1: pre-dose (0 hrs) (Baseline), immediately after tocilizumab and obinutuzumab infusion (1 hr, approximately 7 hrs); C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D8, C1D15, C2D1: pre-dose (0 hrs); C1D3

  19. Change From Baseline in Level of Downstream Biomarker of IL-6 Activation: Soluble IL-6 Receptor (sIL-6R)

    1 cycle=28 days

    Measured: C1D1: pre-dose (0 hrs) (Baseline), immediately after tocilizumab and obinutuzumab infusion (1 hr, approximately 7 hrs); C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D8, C1D15, C2D1: pre-dose (0 hrs); C1D3

  20. Change From Baseline in Level of Downstream Biomarker of IL-6 Activation: Ferritin

    1 cycle=28 days

    Measured: C1D1: pre-dose (0 hrs) (Baseline), immediately after tocilizumab and obinutuzumab infusion (1 hr, approximately 7 hrs); C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D8, C1D15, C2D1: pre-dose (0 hrs); C1D3

  21. Change From Baseline in Level of Downstream Biomarker of IL-6 Activation: C-Reactive Protein (CRP)

    1 cycle=28 days

    Measured: C1D1: pre-dose (0 hrs) (Baseline), immediately after tocilizumab and obinutuzumab infusion (1 hr, approximately 7 hrs); C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D8, C1D15, C2D1: pre-dose (0 hrs); C1D3

  22. Change From Baseline in Level of Downstream Biomarker of IL-6 Activation: Soluble Glycoprotein (gp) 130

    1 cycle=28 days

    Measured: C1D1: pre-dose (0 hrs) (Baseline), immediately after tocilizumab and obinutuzumab infusion (1 hr, approximately 7 hrs); C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D8, C1D15, C2D1: pre-dose (0 hrs); C1D3

  23. Change From Baseline in Level of Downstream Biomarker of IL-6 Activation: Serum Amyloid A (SAA)

    1 cycle=28 days

    Measured: C1D1: pre-dose (0 hrs) (Baseline), immediately after tocilizumab and obinutuzumab infusion (1 hr, approximately 7 hrs); C1D2: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D8, C1D15, C2D1: pre-dose (0 hrs); C1D3

  24. Percentage of Participants With Depletion in Absolute Lymphocyte Count (ALC)

    Measured: C1D1,C1D2,C1D8,C1D15: pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C1D3; C2D1: Pre-dose (0 hrs), immediately after obinutuzumab infusion (approximately 7 hrs); C3D1,C4D1,C5D1,C6D1: pre-dose (0 hrs) (1 cycle=28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2015 (estimated)
  2. Study start26 Jun 2015
  3. Primary completion21 Sep 2018
  4. Study completion21 Sep 2018

Why it stopped: This study was terminated early because premedication with tocilizumab was unlikely to reduce the risk of IRR.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02336048
Sponsor's protocol ID
BO29448
Other IDs
2014-004594-16, 2014
Status last verified
Apr 2021
First submitted
6 Jan 2015
Last updated
8 Apr 2021
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Chlorambucil, Obinutuzumab and Standard Premedication in people with B-Cell Chronic Lymphocytic Leukemia, run by Hoffmann-La Roche at 14 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Israel, Italy, Spain, Latvia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: This study was terminated early because premedication with tocilizumab was unlikely to reduce the risk of IRR.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Baseline up to approximately 196 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02336048.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2021.

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