Chronic Lymphocytic LeukemiaPhase 1NCT02537613
A Study of Ibrutinib + Obinutuzumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
A Phase 1 study testing Obinutuzumab and Ibrutinib in people with Chronic Lymphocytic Leukemia, run by Dana-Farber Cancer Institute at 4 sites in United States.
Trial summary
This research study is evaluating a combination of two drugs, ibrutinib and obinutuzumab, as a possible treatment for Chronic Lymphocytic Leukemia (CLL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- Obinutuzumab and Ibrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 4 sitesUnited States
- Study dates
- Dec 2015to Jan 2027
- Phase
- Phase 1
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
- Must have a confirmed diagnosis of Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma as per IW-CLL 2008 criteria and require therapy based on meeting at least one of the following criteria:
- Evidence of progressive marrow failure with anemia (hemoglobin <11.0 g/L) and/or thrombocytopenia (platelets <100 x 10^9/L)
- Massive (≥6 cm below the left costal margin), progressive, or symptomatic splenomegaly
- Massive nodes (at least 10 cm longest diameter), progressive, or symptomatic lymphadenopathy
- Progressive lymphocytosis with an increase of more than 50% over a 2-month period or LDT of <6 months.
- Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids
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- Constitutional symptoms, defined as 1 or more of the following:
- unintentional weight loss >10% within 6 months prior to screening
- significant fatigue (inability to work or perform usual activities) fevers >100.5° F or 38.0° C for 2 or more weeks prior to screening without evidence of infection
- night sweats for more than 1 month prior to screening without evidence of infection
- Relapsed after or refractory to at least one prior Chronic Lymphocytic Leukemia-directed therapy
- Age greater than or equal to 18 years
- ECOG Performance Status <2
- Heme criteria at screening, unless significant bone marrow involvement of Chronic Lymphocytic Leukemia confirmed on biopsy:
- Absolute Neutrophil Count (ANC) ≥500 cells/mm3 (0.5 x 10^9/L). Growth factor allowed to achieve
- Platelet count ≥25,000 cells/mm3 (25 x 10^9/L) independent of transfusion within 7 days of screening
- Adequate hepatic function defined as: AST and ALT ≤ 4.0 x upper limit of normal (ULN), bilirubin ≤2.0 x upper limit of normal (ULN) unless bilirubin rise is due to Gilbert's syndrome)
- Adequate renal function defined by serum creatinine <2.0 x upper limit of normal (ULN) unless due to biopsy proven Chronic Lymphocytic Leukemia kidney infiltration
- Women of child-bearing potential and men must agree to use adequate contraception
- Patients who have undergone prior allo transplant are eligible provided that their transplant day 0 is > 6 months from their first dose of study drug
Who cannot join
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
- Prior treatment with either obinutuzumab or ibrutinib
- History of other malignancies, except:
- Malignancy treated with curative intent and with no known active disease present for ≥3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- Adequately treated carcinoma in situ without evidence of disease.
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- Low-risk prostate cancer on active surveillance
- Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc., or chronic administration of >20 mg/day of prednisone) within 28 days of the first dose of study drug.
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
- Recent infection requiring systemic treatment that was completed ≤7 days before the first dose of study drug.
- Known bleeding disorders or hemophilia.
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- Known history of HIV or active hepatitis C virus (HCV) or hepatitis B virus (HBV).
- Any uncontrolled active systemic infection.
- Major surgery within 4 weeks of first dose of study drug.
- Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 CHF as defined by the NYHA Functional Classification; or a history of Myocardial Infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
- Lactating or pregnant.
- Patients receiving any other study agents
- Patients with known Central Nervous System involvement
- Baseline QT Interval Corrected by the Fridericia Correction Formula (QTcF) >480 ms unless Left Bundle Branch Block
- Patients who require warfarin or other vitamin K antagonists for anticoagulation
- Concurrent administration of strong inhibitors or inducers of CYP3A
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Duke University Medical Center
Durham, North Carolina, 27710
University of Rochester Wilmot Cancer Inst.
Rochester, New York, 14642
About this study
Official title: A Phase Ib Study of Ibrutinib in Combination With Obinutuzumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
This research study is evaluating a combination of two drugs, ibrutinib and obinutuzumab, as a possible treatment for Chronic Lymphocytic Leukemia (CLL).
Read the detailed description
This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the best order of administration of these two drugs. "Investigational" means that the intervention is being studied. The FDA (the U.S. Food and Drug Administration) has approved ibrutinib and obinutuzumab individually for the treatment of patients with Chronic Lymphocytic Leukemia, your type of cancer. However, the FDA has not approved the combination of these two drugs as a treatment for any disease.
Ibrutinib is a type of drug called a kinase inhibitor. It is believed to block a type of protein called a kinase that helps leukemia cells live and grow. By blocking this, it is possible that the study drug will kill cancer cells or stop them from growing.
Obinutuzumab is a type of drug called a monoclonal antibody. It is believed to attach to a protein called CD20 on the outside of a Chronic Lymphocytic Leukemia cell. By attaching to the cell, the antibody can cause the Chronic Lymphocytic Leukemia cell to die.
In this research study, the investigators are assessing the safety of various dosing regimens of ibrutinib and obinutuzumab. The investigators are trying to determine whether it is better to give one drug before the other or if they can be started at the same time.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Obinutuzumab, Ibrutinib
- Keywords
- Chronic Lymphocytic Leukemia
- 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.
ObinutuzumabDrug
Also called Gazyva, GA-101
Obinutuzumab given weekly during cycle 1, then monthly during cycles 2-6
IbrutinibDrug
Also called Imbruvica
Ibrutinib given once daily by mouth
| Study group | Role | What they receive |
|---|---|---|
| Arm A- obinutuzumab -> ibrutinib | Experimental | Participants enrolled in Arm A will receive obinutuzumab weekly starting cycle 1, and will receive obinutuzumab monthly during cycles 2-6. Participants will begin to take ibrutinib daily starting cycle 2 and will continue with daily ibrutinib until the end of treatment. Receives: Drug: Obinutuzumab; Drug: Ibrutinib |
| Arm B- ibrutinib -> obinutuzumab | Experimental | Participants enrolled in Arm B will begin to take ibrutinib daily starting cycle 1 and will continue with daily ibrutinib until the end of treatment. Participants will begin to receive obinutuzumab weekly starting cycle 2, and will receive obinutuzumab monthly during cycles 3-7 Receives: Drug: Obinutuzumab; Drug: Ibrutinib |
| Arm C- obinutuzumab/ibrutinib | Experimental | Participants enrolled in Arm C will begin to take ibrutinib daily starting cycle 1 and will continue with daily ibrutinib until the end of treatment. At the same time, participants will begin to receive obinutuzumab weekly starting cycle 1, and will receive obinutuzumab monthly during cycles 2-6. Receives: Drug: Obinutuzumab; Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Grade 3-5 Treatment-related Toxicity Rate
All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 that are not resolved in accordance with treatment guidelines were counted. Rate is the proportion of treated participants experiencing at least one of these adverse events as defined during the time of observation.
Measured: AE evaluated at cycle 1 day day 1, 2, 8 and 15; cycle 2 day 1, 8, 15 and 22; then each cycle day 1 until end of treatment.
Secondary outcomes (5)
Overall Response Rate (ORR)
The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on Chronic Lymphocytic Leukemia (IW-CLL) criteria.
Measured: Disease screening at baseline, cycle 3-7 at day one and end of treatment or disease progression (PD). Median (range) duration of treatment is 29.9 (range 0.5, 98.1) months.
Partial Response Rate (PRR)
The PRR was defined as the proportion of participants achieving partial response (PR) based on Chronic Lymphocytic Leukemia (IW-CLL) criteria.
Measured: Disease screening at baseline, cycle 3-7 at day one and end of treatment or disease progression (PD). Median (range) duration of treatment is 29.9 (range 0.5, 98.1) months.
Complete Response Rate (CRR)
The CRR was defined as the proportion of participants achieving complete response (CR) based on Chronic Lymphocytic Leukemia (IW-CLL) criteria.
Measured: Disease screening at baseline, cycle 3-7 at day one and end of treatment or disease progression (PD). Median (range) duration of treatment is 29.9 (range 0.5, 98.1) months.
Minimal Residual Disease (MRD) Rate
MRD rate was defined as the proportion of participants achieving MRD in bone marrow
Measured: Disease screening at baseline, cycle 3-7 at day one and end of treatment or disease progression (PD).
Median Progression-Free Survival (PFS)
Progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) or death, or is censored at time of last dsease assessment.
Measured: Through final follow-up visit (up to 9.63 years).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2015 (estimated)
- Study startDec 2015
- Primary completionMar 2020
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Matthew S. Davids, MD, Dana-Farber Cancer Institute
- Investigators
- Matthew Davids, MD, MMSc, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02537613
- Sponsor's protocol ID
- 15-283
- Status last verified
- Sep 2026
- First submitted
- 27 Aug 2015
- Last updated
- 22 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No