Chronic Lymphocytic LeukemiaPhase 1/2NCT02427451
Bcl-2 Inhibitor GDC-0199 in Combination With Obinutuzumab and Ibrutinib in Treating Patients With Relapsed, Refractory, or Previously Untreated Chronic Lymphocytic Leukemia
A Phase 1/2 study testing Bcl-2 Inhibitor GDC-0199, Obinutuzumab and Ibrutinib in people with Chronic Lymphocytic Leukemia and Refractory Chronic Lymphocytic Leukemia, run by Kerry Rogers at 1 site in United States.
Trial summary
This phase Ib/II trial studies the best dose and safety of Bcl-2 inhibitor GDC-0199 in combination with obinutuzumab and ibrutinib and to see how well they work in treating patients with chronic lymphocytic leukemia that has returned (relapsed), does not respond to treatment (refractory), or is previously untreated. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia
- What is being tested?
- Bcl-2 Inhibitor GDC-0199, Obinutuzumab and Ibrutinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Aug 2015to 15 Apr 2027
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Diagnosis of CLL meeting criteria established in the World Health Organization (WHO) classification of hematologic disorders
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- Relapsed or refractory CLL patients must meet the following requirements:
- Received at least 1 prior therapy
- Require treatment in the opinion of the investigator
- Relapsed patients must have developed progressive disease following a response to a prior therapy
Show all 30Show fewer
- Refractory patients must have failed to respond or relapsed within 6 months to the last prior therapy
- Treatment-naïve CLL patients must meet the following requirements (Phase II only):
- Symptomatic disease as defined by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria
- Received no prior chemotherapy, immunotherapy, or targeted therapy for the treatment of CLL with the exceptions of palliative loco-regional radiotherapy and corticosteroids for symptom control
- Hemoglobin >= 8 g/dL
- Absolute neutrophil count (ANC) >= 1000/mm^3
- Platelets >= 40,000/mm^3
- Prothrombin time (PT)/partial thromboplastin time (PTT) =< 1.5 x upper limit of normal (ULN)
- Total bilirubin =< 1.5 x ULN (excepting Gilbert's syndrome)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 × ULN
- Serum creatinine < 2.0 mg/dL or creatinine clearance (Cockcroft) >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Female patients must be surgically sterile, post-menopausal (for at least 1 year), or have negative results from a pregnancy test performed as follows:
- At screening, on a serum sample obtained within 14 days prior to the first study drug administration, and
- Prior to dosing, on a urine sample obtained on day 1 of treatment if it has been > 7 days since obtaining the serum pregnancy test result
- All female patients not surgically sterile or post-menopausal (for at least 1 year) and non-vasectomized male patients must practice at least one of the following methods of birth control:
- Total abstinence from sexual intercourse (minimum one complete menstrual cycle)
- A vasectomized partner
- Hormonal contraceptives for at least 2 months prior to day 1 of treatment
- Double-barrier method
- Non-vasectomized male patients must practice at least one of the following methods of birth control throughout the duration of study participation and for at least 3 months after study treatment:
- A partner who is surgically sterile or postmenopausal (for at least 1 year) or who is taking hormonal contraceptives (oral, parenteral, vaginal ring, or transdermal) for at least 3 months prior to study drug administration
- Total abstinence from sexual intercourse
- Double-barrier method (condom, diaphragm or cervical cup with spermicidal, contraceptive sponge, jellies, or cream)
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients who have had chemotherapy, immunotherapy, radiotherapy, or investigational therapy within 28 days prior to entering the study or those who have not recovered from adverse events due to agents administered more than 28 days earlier; steroids for control of disease related symptoms are permitted
- Patients who are receiving any other investigational agents
- Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
- Active Richter's transformation
- Known active involvement of the central nervous system by lymphoma or leukemia
- Patients who require warfarin anticoagulation or who have received warfarin or equivalent vitamin K antagonists =< 7 days prior to treatment day 1; patients may be eligible if able to be taken off warfarin and started on an alternative anticoagulant
Show all 28Show fewer
- Received potent cytochrome P450 3A4 (CYP3A4) inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 7 days prior to the first dose of study treatment
- Received potent CYP3A4 inducers (such as rifampin, carbamazepine, phenytoin, St. John's wort) within 7 days prior to the first dose of study treatment
- Consumed grapefruit or grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study treatment
- History of a prior significant toxicity, other than thrombocytopenia, from another Bcl-2 family protein inhibitor
- Known cysteine-481 Bruton's tyrosine kinase (BTK) mutation or CLL refractory to or progressed during ibrutinib or other Cys-481 binding BTK inhibitor treatment
- Known infection with the human immunodeficiency virus (HIV) virus
- A cardiovascular disability status of New York Heart Association class >= 2, defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or angina pain
- Positive hepatitis serology:
- Hepatitis B virus (HBV): patients with positive serology for hepatitis B defined as positivity for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc); patients who are positive for anti-HBc may be considered for inclusion in the study on a case-by-case basis if they are hepatitis B viral deoxyribonucleic acid (DNA) negative and are willing to undergo ongoing HBV DNA testing by real-time polymerase chain reaction (PCR); patients with positive serology may be referred to a hepatologist or gastroenterologist for appropriate monitoring and management
- Patients with positive HBSAg consistent with prior vaccination to HBV (i.e., anti-HBs+, anti-HBc-) may participate
- Patients suspected to have false positive serologic studies because of IV immunoglobulin administration are potentially eligible after negative PCR studies for viral DNA/ribonucleic acid (RNA) and discussion with the principal investigator
- Hepatitis C (HCV): patients with positive hepatitis C serology unless HCV RNA is confirmed negative and may be considered for inclusion in the study on a case-by-case basis (e.g., patients with negative viral load after HCV-specific treatment)
- History of severe (defined as grade 4 and/or requiring permanent discontinuation of prior antibody therapy) allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies
- Patients who received a live viral vaccination within 6 months prior to the first dose of study drug
- A female patient who is pregnant or breast-feeding
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- History of other active malignancies other than CLL within the past 3 years prior to study entry, with the exception of:
- Adequately treated in situ carcinoma or the cervix uteri or breast
- Basal cell or localized squamous cell carcinoma of the skin
- Previous malignancy confirmed and surgically resected (or treated with other modalities) with curative intent or without relapse for >= 2 years
- Vaccination with a live vaccine < 28 days prior to the start of treatment
- Inability to swallow capsules or tablets, or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption (malabsorption syndrome, resection of the small bowel, poorly controlled inflammatory bowel disease, etc.)
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
About this study
Official title: Obinutuzumab, Ibrutinib, and Venetoclax for Relapsed and Previously Untreated Chronic Lymphocytic Leukemia (CLL)
This phase Ib/II trial studies the best dose and safety of Bcl-2 inhibitor GDC-0199 in combination with obinutuzumab and ibrutinib and to see how well they work in treating patients with chronic lymphocytic leukemia that has returned (relapsed), does not respond to treatment (refractory), or is previously untreated. Bcl-2 inhibitor GDC-0199 and ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as obinutuzumab, may block cancer growth in different ways by targeting certain cells. Giving Bcl-2 inhibitor GDC-0199 together with obinutuzumab and ibrutinib may be a better treatment for chronic lymphocytic leukemia.
Read the detailed description
PRIMARY OBJECTIVES:
- To identify the dose of venetoclax (Bcl-2 inhibitor GDC-0199) that can be safely administered in combination with obinutuzumab and ibrutinib for the treatment of relapsed/refractory or previously untreated chronic lymphocytic leukemia (CLL).
II. To evaluate the feasibility, safety, and tolerability of venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated CLL.
III. To determine the minimal residual disease (MRD)-negative complete response (CR) rate after 12 cycles of treatment with venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated CLL.
SECONDARY OBJECTIVES:
- To determine the overall response rate (ORR) and complete response rate (CR) of venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated patients with CLL.
II. To estimate progression free survival (PFS) after treatment with venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated patients with CLL.
III. To conduct pharmacokinetic and pharmacodynamic studies of venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated patients with CLL.
IV. To examine pre-treatment and serial biomarkers associated with response and mechanisms of resistance to venetoclax, obinutuzumab and ibrutinib when given in combination for relapsed/refractory or previously untreated patients with CLL.
OUTLINE: This is a phase Ib, dose-escalation study of Bcl-2 inhibitor GDC-0199 followed by a phase II study.
Patients receive obinutuzumab intravenously (IV) on day 1 (days 1, 2, 8, and 15 for course 1 only) every 28 days for up to 8 courses. Beginning in course 2, patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Beginning in course 3, patients receive Bcl-2 inhibitor GDC-0199 PO QD on days 1-28. Treatment repeats every 28 days for up to 14 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4 and 8 weeks, every 3 months for 2 years, and then every 6 months thereafter.
- Being tested
- Bcl-2 Inhibitor GDC-0199, Obinutuzumab, Ibrutinib, Pharmacological Study, Laboratory Biomarker Analysis
- 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.
Bcl-2 Inhibitor GDC-0199Drug
Also called ABT-0199, ABT-199, GDC-0199, RG7601
Given PO
ObinutuzumabBiological
Also called Anti-CD20 Monoclonal Antibody R7159, GA101, Gazyva, R7159
Given IV
IbrutinibDrug
Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765
Given PO
Also called pharmacological studies
Correlative studies
Laboratory Biomarker AnalysisOther
Correlative studies
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199) | Experimental | Patients receive obinutuzumab IV on day 1 (days 1, 2, 8, and 15 for course 1 only) every 28 days for up to 8 courses. Beginning in course 2, patients receive ibrutinib PO QD on days 1-28. Beginning in course 3, patients receive Bcl-2 inhibitor GDC-0199 PO QD on days 1-28. Treatment repeats every 28 days for up to 14 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Bcl-2 Inhibitor GDC-0199; Biological: Obinutuzumab; Drug: Ibrutinib; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose of Bcl-2 Inhibitor GDC-0199 in Combination With Obinutuzumab and Ibrutinib (Phase Ib)
Measured: 28 days (course 3)
Minimal Residual Disease (MRD)-Complete Response (CR) Defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria (Phase II)
Assessments of MRD will be used in patients classified as CR to further evaluate their status as disease-free and if this further impacts their ability to remain progression-free and alive. MRD will be determined by high sensitivity 4 color flow cytometric analysis of the bone marrow using validated panels.
Measured: Up to 8 weeks post-treatment
Secondary outcomes (17)
Number of Adverse Events Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
For all patients who receive at least one day of treatment, toxicities will be tabulated by type and grade and displayed in summary form. Serious adverse events are listed with "(SAE)" after the event name.
Measured: Up to 4 years
Number of Courses Started/Completed
May be summarized.
Measured: Up to 14 months
Number of Patients Who Reach the Target Dose of Bcl-2 Inhibitor GDC-0199
May be summarized.
Measured: Up to 14 months
Number of Patients Requiring Dose Reductions
May be summarized.
Measured: Up to 14 months
Reason for Going Off Treatment
May be summarized.
Measured: Up to 14 months
Overall Response Rate
Overall response rate will be reported for all evaluable patients in the phase II setting, within and potentially across cohorts, assuming a binomial distribution.
Measured: Up to 4 years
Progression-free Survival (PFS)
Will be summarized by the Kaplan-Meier method for each of the phase II cohorts.
Measured: Time from first treatment date until the date of progression or death, whichever occurs first, assessed up to 8 years
Emotional Distress Assessment
Validated instruments will be administered serially to assess longitudinal changes in measures of health related quality of life using 36-Item Short Form Survey (SF-36) Mental Component Scale (MCS) T-scores for each time point with pairwise comparison p-values. Scores on the SF-36 scale range from 0 to 100, with higher scores indicating better mental health. Scores for the MCS are standardized using U.S. general population norms with summary scores set relative to a t-score mean of 50 and a standard deviation of 10.
Measured: Cycle 1 day 1, cycle 2 day 1, cycle 3 day 1, cycle 6 day 1 and cycle 12 day 1
Health Related Quality of Life
Validated instruments will be administered serially to assess longitudinal changes in measures of health related quality of life using 36-Item Short Form Survey (SF-36) Physical Component Scale (PCS) T-scores for each time point with pairwise comparison p-values. Scores on the SF-36 scale range from 0 to 100, with higher scores indicating better physical health. Scores for the PCS are standardized using U.S. general population norms with summary scores set relative to a t-score mean of 50 and a standard deviation of 10.
Measured: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 6 Day 1, and Cycle 12 Day 1 (each cycle is 28 days)
Serial Assessment of Immune Effector Cell Number and Function.
Peripheral blood immunophenotyping will be used to enumerate immune effector cells (counts and percentages of T-, and Natural Killer (NK)-cell subsets).
Measured: 4 weeks post-treatment
Baseline Prognostic Factors: Number of Prior Therapies
Relationships between baseline prognostic factors and response may be screened and analyzed quantitatively using logistic regression and adjusting for disease cohort, particularly if a sufficient number of patients respond to this combination therapy.
Measured: Baseline
Baseline Prognostic Factors: Tumor Lysis Syndrome (TLS) Risk
Relationships between baseline prognostic factors and response may be screened and analyzed quantitatively using logistic regression and adjusting for disease cohort, particularly if a sufficient number of patients respond to this combination therapy.
Measured: Baseline
Baseline Prognostic Factors: Hemoglobin
Measured: Baseline
Baseline Prognostic Factors: Investigations
Absolute neutrophil count (ANC), Absolute lymphocyte count (ALC) and Platelets.
Measured: Baseline
Baseline Prognostic Factor: Beta-2-microglobulin (B2M)
Beta-2-microglobulin (B2M)
Measured: At baseline
Baseline Prognostic Factors: Lactate Dehydrogenase (LDH)
lactate dehydrogenase (LDH)
Measured: At baseline
Baseline Prognostic Factors: Genetic Factors
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2015 (estimated)
- Study start3 Aug 2015
- Primary completion24 Dec 2021
- Study completion15 Apr 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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kerry Rogers
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Kerry Rogers, Ohio State University Comprehensive Cancer Center
- Investigators
- Kerry Rogers, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02427451
- Sponsor's protocol ID
- OSU-14266
- Other IDs
- NCI-2015-00252
- Status last verified
- May 2026
- First submitted
- 4 Mar 2015
- Last updated
- 15 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Arrato NA, Valentine TR, Byrd JC, Jones JA, Maddocks KJ, Woyach JA, Andersen BL. Illness representations and psychological outcomes in chronic lymphocytic leukaemia. Br J Health Psychol. 2022 May;27(2):553-570. doi: 10.1111/bjhp.12562. Epub 2021 Oct 4.
PubMed 34608724Rogers KA, Huang Y, Ruppert AS, Abruzzo LV, Andersen BL, Awan FT, Bhat SA, Dean A, Lucas M, Banks C, Grantier C, Heerema NA, Lozanski G, Maddocks KJ, Valentine TR, Weiss DM, Jones JA, Woyach JA, Byrd JC. Phase II Study of Combination Obinutuzumab, Ibrutinib, and Venetoclax in Treatment-Naive and Relapsed or Refractory Chronic Lymphocytic Leukemia. J Clin Oncol. 2020 Nov 1;38(31):3626-3637. doi: 10.1200/JCO.20.00491. Epub 2020 Aug 14.
PubMed 32795224Rogers KA, Huang Y, Ruppert AS, Awan FT, Heerema NA, Hoffman C, Lozanski G, Maddocks KJ, Moran ME, Reid MA, Lucas M, Woyach JA, Whitlow WT, Jones JA, Byrd JC. Phase 1b study of obinutuzumab, ibrutinib, and venetoclax in relapsed and refractory chronic lymphocytic leukemia. Blood. 2018 Oct 11;132(15):1568-1572. doi: 10.1182/blood-2018-05-853564. Epub 2018 Aug 15.
PubMed 30111609
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Obinutuzumab, Ibrutinib, and Venetoclax for Relapsed and Previously Untreated Chronic Lymphocytic Leukemia (CLL)
- ClinicalTrials.gov ID
- NCT02427451
- Acronym / sponsor ID
- OSU-14266
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Kerry RogersUniversity, hospital or other
- Study start
- 3 Aug 2015 (actual)
- Primary completion
- 24 Dec 2021 (actual)
- Study completion
- 15 Apr 2027 (estimated)
- First posted
- 28 Apr 2015 (estimated)
- Results
- Posted 27 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase Ib/II trial studies the best dose and safety of Bcl-2 inhibitor GDC-0199 in combination with obinutuzumab and ibrutinib and to see how well they work in treating patients with chronic lymphocytic leukemia that has returned (relapsed), does not respond to treatment (refractory), or is previously untreated. Bcl-2 inhibitor GDC-0199 and ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as obinutuzumab, may block cancer growth in different ways by targeting certain cells. Giving Bcl-2 inhibitor GDC-0199 together with obinutuzumab and ibrutinib may be a better treatment for chronic lymphocytic leukemia.
Detailed description
PRIMARY OBJECTIVES:
- To identify the dose of venetoclax (Bcl-2 inhibitor GDC-0199) that can be safely administered in combination with obinutuzumab and ibrutinib for the treatment of relapsed/refractory or previously untreated chronic lymphocytic leukemia (CLL).
II. To evaluate the feasibility, safety, and tolerability of venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated CLL.
III. To determine the minimal residual disease (MRD)-negative complete response (CR) rate after 12 cycles of treatment with venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated CLL.
SECONDARY OBJECTIVES:
- To determine the overall response rate (ORR) and complete response rate (CR) of venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated patients with CLL.
II. To estimate progression free survival (PFS) after treatment with venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated patients with CLL.
III. To conduct pharmacokinetic and pharmacodynamic studies of venetoclax in combination with obinutuzumab and ibrutinib in patients with relapsed/refractory or previously untreated patients with CLL.
IV. To examine pre-treatment and serial biomarkers associated with response and mechanisms of resistance to venetoclax, obinutuzumab and ibrutinib when given in combination for relapsed/refractory or previously untreated patients with CLL.
OUTLINE: This is a phase Ib, dose-escalation study of Bcl-2 inhibitor GDC-0199 followed by a phase II study.
Patients receive obinutuzumab intravenously (IV) on day 1 (days 1, 2, 8, and 15 for course 1 only) every 28 days for up to 8 courses. Beginning in course 2, patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Beginning in course 3, patients receive Bcl-2 inhibitor GDC-0199 PO QD on days 1-28. Treatment repeats every 28 days for up to 14 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4 and 8 weeks, every 3 months for 2 years, and then every 6 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199) | Experimental | Drug: Bcl-2 Inhibitor GDC-0199, Biological: Obinutuzumab, Drug: Ibrutinib, Other: Pharmacological Study, Other: Laboratory Biomarker Analysis, Other: Quality-of-Life AssessmentPatients receive obinutuzumab IV on day 1 (days 1, 2, 8, and 15 for course 1 only) every 28 days for up to 8 courses. Beginning in course 2, patients receive ibrutinib PO QD on days 1-28. Beginning in course 3, patients receive Bcl-2 inhibitor GDC-0199 PO QD on days 1-28. Treatment repeats every 28 days for up to 14 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Diagnosis of CLL meeting criteria established in the World Health Organization (WHO) classification of hematologic disorders
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- Relapsed or refractory CLL patients must meet the following requirements:
- Treatment-naïve CLL patients must meet the following requirements (Phase II only):
- Hemoglobin >= 8 g/dL
Key exclusion criteria (28 listed)
- Patients who have had chemotherapy, immunotherapy, radiotherapy, or investigational therapy within 28 days prior to entering the study or those who have not recovered from adverse events due to agents administered more than 28 days earlier; steroids for control of disease related symptoms are permitted
- Patients who are receiving any other investigational agents
- Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
- Active Richter's transformation
- Known active involvement of the central nervous system by lymphoma or leukemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bcl-2 Inhibitor GDC-0199Also: ABT-0199, ABT-199, GDC-0199, RG7601Given PO | Drug | Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199) |
| ObinutuzumabAlso: Anti-CD20 Monoclonal Antibody R7159, GA101, Gazyva, R7159Given IV | Biological | Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199) |
| IbrutinibAlso: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765Given PO | Drug | Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199) |
| Pharmacological StudyAlso: pharmacological studiesCorrelative studies | Other | Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199) |
Primary outcome
Maximum Tolerated Dose of Bcl-2 Inhibitor GDC-0199 in Combination With Obinutuzumab and Ibrutinib (Phase Ib)
Time frame: 28 days (course 3)
Minimal Residual Disease (MRD)-Complete Response (CR) Defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria (Phase II)
Time frame: Up to 8 weeks post-treatment
Assessments of MRD will be used in patients classified as CR to further evaluate their status as disease-free and if this further impacts their ability to remain progression-free and alive. MRD will be determined by high sensitivity 4 color flow cytometric analysis of the bone marrow using validated panels.
17 secondary outcomes
Number of Adverse Events Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Time frame: Up to 4 years
Number of Courses Started/Completed
Time frame: Up to 14 months
Number of Patients Who Reach the Target Dose of Bcl-2 Inhibitor GDC-0199
Time frame: Up to 14 months
Number of Patients Requiring Dose Reductions
Time frame: Up to 14 months
Reason for Going Off Treatment
Time frame: Up to 14 months
Overall Response Rate
Time frame: Up to 4 years
Progression-free Survival (PFS)
Time frame: Time from first treatment date until the date of progression or death, whichever occurs first, assessed up to 8 years
Emotional Distress Assessment
Time frame: Cycle 1 day 1, cycle 2 day 1, cycle 3 day 1, cycle 6 day 1 and cycle 12 day 1
Health Related Quality of Life
Time frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 6 Day 1, and Cycle 12 Day 1 (each cycle is 28 days)
Serial Assessment of Immune Effector Cell Number and Function.
Time frame: 4 weeks post-treatment
Baseline Prognostic Factors: Number of Prior Therapies
Time frame: Baseline
Baseline Prognostic Factors: Tumor Lysis Syndrome (TLS) Risk
Time frame: Baseline
Baseline Prognostic Factors: Hemoglobin
Time frame: Baseline
Baseline Prognostic Factors: Investigations
Time frame: Baseline
Baseline Prognostic Factor: Beta-2-microglobulin (B2M)
Time frame: At baseline
Baseline Prognostic Factors: Lactate Dehydrogenase (LDH)
Time frame: At baseline
Baseline Prognostic Factors: Genetic Factors
Time frame: At baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34608724Arrato NA, Valentine TR, Byrd JC, Jones JA, Maddocks KJ, Woyach JA, Andersen BL. Illness representations and psychological outcomes in chronic lymphocytic leukaemia. Br J Health Psychol. 2022 May;27(2):553-570. doi: 10.1111/bjhp.12562. Epub 2021 Oct 4.
- Derived from this study: PubMed 32795224Rogers KA, Huang Y, Ruppert AS, Abruzzo LV, Andersen BL, Awan FT, Bhat SA, Dean A, Lucas M, Banks C, Grantier C, Heerema NA, Lozanski G, Maddocks KJ, Valentine TR, Weiss DM, Jones JA, Woyach JA, Byrd JC. Phase II Study of Combination Obinutuzumab, Ibrutinib, and Venetoclax in Treatment-Naive and Relapsed or Refractory Chronic Lymphocytic Leukemia. J Clin Oncol. 2020 Nov 1;38(31):3626-3637. doi: 10.1200/JCO.20.00491. Epub 2020 Aug 14.
- Derived from this study: PubMed 30111609Rogers KA, Huang Y, Ruppert AS, Awan FT, Heerema NA, Hoffman C, Lozanski G, Maddocks KJ, Moran ME, Reid MA, Lucas M, Woyach JA, Whitlow WT, Jones JA, Byrd JC. Phase 1b study of obinutuzumab, ibrutinib, and venetoclax in relapsed and refractory chronic lymphocytic leukemia. Blood. 2018 Oct 11;132(15):1568-1572. doi: 10.1182/blood-2018-05-853564. Epub 2018 Aug 15.
- The JameslineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kerry Rogers, MD principal investigator
Ohio State University Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bcl-2 Inhibitor GDC-0199, Obinutuzumab and Ibrutinib in people with Chronic Lymphocytic Leukemia and Refractory Chronic Lymphocytic Leukemia, run by Kerry Rogers at 1 site in United States.
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 30 inclusion and 28 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: under way, not looking for participants, as of the sponsor's last update on 15 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Tolerated Dose of Bcl-2 Inhibitor GDC-0199 in Combination With Obinutuzumab and Ibrutinib (Phase Ib) (time frame: 28 days (course 3)). The study lists 2 primary outcomes in all. 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 NCT02427451, which also lists 3 linked publications.
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 15 Jun 2026.