Bcl-2 Inhibitor GDC-0199 in Combination With Obinutuzumab and Ibrutinib in Treating Patients With Relapsed, Refractory, or Previously Untreated Chronic Lymphocytic Leukemia

NCT02427451 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: OSU-14266NCI-2015-00252
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose of Bcl-2 Inhibitor GDC-0199 in Combination With Obinutuzumab and Ibrutinib (Phase Ib)

  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.

  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

  Up to 4 years

• Number of Courses Started/Completed

  Up to 14 months

• Number of Patients Who Reach the Target Dose of Bcl-2 Inhibitor GDC-0199

  Up to 14 months

• Number of Patients Requiring Dose Reductions

  Up to 14 months

• Reason for Going Off Treatment

  Up to 14 months

Study Arms (1)

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.

Drug: Bcl-2 Inhibitor GDC-0199; Biological: Obinutuzumab; Drug: Ibrutinib; Other: Pharmacological Study; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment

Interventions

Bcl-2 Inhibitor GDC-0199 DRUG

Given PO

Also known as: ABT-0199, ABT-199, GDC-0199, RG7601

Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA101, Gazyva, R7159, RO 5072759

Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199)

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199)

Pharmacological Study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (obinutuzumab, ibrutinib, Bcl-2 inhibitor GDC-0199)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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:
• Patients with positive HBSAg consistent with prior vaccination to HBV (i.e., anti-HBs+, anti-HBc-) may participate

Sponsors & Collaborators

• Kerry Rogers: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (3)

• 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.

  PMID: 34608724 DERIVED

• Rogers 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.

  PMID: 32795224 DERIVED

• Rogers 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.

  PMID: 30111609 DERIVED

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

venetoclax; obinutuzumab; ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Kerry Rogers
• Organization: The Ohio State University Comprehensive Cancer Center

Kerry.Rogers@osumc.edu

614-293-3873

Study Officials

• Kerry Rogers, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 4, 2015
• First Posted: April 28, 2015
• Study Start: August 3, 2015
• Primary Completion: December 24, 2021
• Study Completion: April 15, 2026
• Last Updated: January 27, 2026
• Results First Posted: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)