Phase 3
Completed N=445
Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia
Lymphocytic Leukemia, Chronic
Source: ClinicalTrials.gov NCT02242942 ↗
Enrolled (actual)
445
Serious AEs
46.5%
Results posted
Oct 2019
Primary outcomePrimary: Progression Free Survival (PFS) Based on Investigator Assessment According to IWCLL Criteria — NA; NA months — p=<0.0001
◆ Published Evidence
Highly cited
117citations · ~59 / year
Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study.
Summary
This open-label, multicenter, randomized Phase III study is designed to compare the efficacy and safety of a combined regimen of obinutuzumab and venetoclax versus obinutuzumab + chlorambucil in participants with chronic lymphocytic leukemia (CLL) and coexisting medical conditions. The time on study treatment was approximately one year and the follow-up period will be up to 9 years
Linked Publications (5)
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Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study.
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Transcriptomic profiles and 5-year results from the randomized CLL14 study of venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab in chronic lymphocytic leukemia.
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Reassessing the chronic lymphocytic leukemia International Prognostic Index in the era of targeted therapies.
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Bioavailability Evaluation of Venetoclax Lower-Strength Tablets and Oral Powder Formulations to Establish Interchangeability with the 100 mg Tablet.
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Indirect Comparisons of the Efficacy and Safety of Zanubrutinib versus Venetoclax plus Obinutuzumab in Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression Free Survival (PFS) Based on Investigator Assessment According to IWCLL Criteria |
NA; NA | <0.0001 sig |
| SECONDARY Progression Free Survival (PFS) Based on Institutional Review Committee (IRC)-Assessments According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria |
NA; NA | <0.0001 sig |
| SECONDARY Percentage of Participants With an Overall Response (OR) at Completion of Treatment, as Determined by the Investigator According to IWCLL Criteria |
71.3; 84.7 | 0.0007 sig |
| SECONDARY Percentage of Participants With a Complete Response Rate (CRR) at the Completion of Treatment Assessment as Determined by the Investigator According to IWCLL Criteria |
23.1; 49.5 | <0.0001 sig |
| SECONDARY Percentage of Participants With Minimal Residual Disease (MRD) Negativity in Peripheral Blood as Measured by Allele-Specific Oligonucleotide Polymerase Chain Reaction (ASO-PCR) at Completion of Treatment |
35.2; 75.5 | <0.0001 sig |
| SECONDARY Percentage of Participants With MRD Negativity in Bone Marrow as Measured by ASO-PCR at Completion of Treatment |
17.1; 56.9 | <0.0001 sig |
| SECONDARY Overall Survival (OS) |
— | — |
| SECONDARY Percentage of Participants With MRD Negativity in Peripheral Blood as Measured by ASO-PCR at Completion of Combination Treatment Assessment |
38.4; 71.3 | <0.0001 sig |
| SECONDARY Percentage of Participants With MRD Negativity in Bone Marrow as Measured by ASO-PCR at Completion of Combination Treatment Assessment |
13.0; 51.4 | <0.0001 sig |
| SECONDARY Percentage of Participants With OR at Completion of Combination Treatment Response Assessment |
86.6; 88.4 | 0.5612 |
| SECONDARY Duration of Objective Response (DOR) |
— | — |
| SECONDARY Percentage of Participants By Best Response Achieved (CR, CRi, PR, Stable Disease (SD), or PD) |
56.0; 70.4; 5.6; 7.9; 29.2; 13.4 | 0.7169 |
| SECONDARY Event-Free Survival |
— | — |
| SECONDARY Time to Next Anti-Leukemic Treatment |
— | — |
| SECONDARY Number of Participants With Adverse Events (AEs) |
— | — |
| SECONDARY Percentage of Participants With CD19 + /CD5+ B Cells or CD14+ Monocytes |
— | — |
| SECONDARY Percentage of Participants With Human-Anti-Human Antibodies |
— | — |
| SECONDARY Percentage of Participants Recorded as Premature Study Withdrawals |
— | — |
| SECONDARY Plasma Concentrations of Venetoclax |
0.578; 1.21 | — |
| SECONDARY Serum Concentrations of Obinutuzumab |
258; 568 | — |
| SECONDARY Change From Baseline in M.D. Anderson Symptom Inventory-CLL (MDASI-CLL) Score |
— | — |
| SECONDARY Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQC30) |
— | — |
| SECONDARY Change From Baseline in EuroQol 5 Dimension Questionnaire (EQ-5D-3L) |
— | — |
Eligibility Criteria
Inclusion Criteria
- Documented previously untreated CLL according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
- CLL requiring treatment according to IWCLL criteria
- Total Cumulative Illness Rating Scale (CIRS score) greater than (>) 6
- Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening as per protocol, unless cytopenia is due to marrow involvement of CLL
- Adequate liver function
- Life expectancy > 6 months
- Agreement to use highly effective contraceptive methods per protocol
Exclusion Criteria
- Transformation of CLL to aggressive Non-Hodgkin's lymphoma (Richter's transformation or pro-lymphocytic leukemia)
- Known central nervous system involvement
- Participants with a history of confirmed progressive multifocal leukoencephalopathy (PML)
- An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system
- Participants with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
- Inadequate renal function
- History of prior malignancy, except for conditions as listed in the protocol if participants have recovered from the acute side effects incurred as a result of previous therapy
- Use of investigational agents or concurrent anti-cancer treatment within the last 4 weeks of registration
- Participants with active bacterial, viral, or fungal infection requiring systemic treatment within the last two months prior to registration
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
- Hypersensitivity to chlorambucil, obinutuzumab, or venetoclax or to any of the excipients
- Pregnant women and nursing mothers
- Positive test results for chronic hepatitis B virus (HBV) infection (defined as positive hepatitis B surface antigen [HBsAg] serology) or positive test result for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
- Participants with known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus-1 (HTLV-1)
- Requires the use of warfarin, marcumar, or phenprocoumon
- Received agents known to be strong and moderate Cytochrome P450 3A inhibitors or inducers within 7 days prior to the first dose of study drug
Data sourced from ClinicalTrials.gov (NCT02242942) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.