Study of the Use of Venetoclax in Participants With Chronic Lymphocytic Leukemia (CLL) Under Real-Life Setting

Study Overview
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Brief Summary
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An observational study to assess the effectiveness, health economic-relevant costs and participant reported outcomes in participants with Chronic lymphocytic leukemia (CLL) receiving venetoclax as a monotherapy or in combination with rituximab or obinutuzumab as prescribed at the discretion of the physician and in accordance with local clinical practice and label.

Official Title
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Observational Study of the Use of Venetoclax in Patients With Chronic Lymphocytic Leukemia (CLL) Under Real-Life Setting in Austria, Germany and Switzerland

Conditions
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Chronic Lymphocytic Leukemia (CLL)

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant with chronic lymphocytic leukemia (CLL) administering venetoclax and who meets the following conditions as specified in the label for venetoclax: Venetoclax monotherapy for the treatment of CLL in the presence of deletion chromosome 17 (del[17p]) or tumor protein p53 (TP53) mutation in adult participants, who are unsuitable for or have failed to a B-cell receptor pathway inhibitor. Venetoclax monotherapy for the treatment of CLL in the absence of del(17p) or TP53 mutation in adult participants, who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor. Venetoclax in combination with rituximab for the treatment of adult participants with CLL who have received at least one prior therapy. Venetoclax in combination with obinutuzumab for previously untreated adult participants with CLL. Exclusion Criteria: - None

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants Receiving Venetoclax<br>Participants with Chronic Lymphocytic Leukemia (CLL) receiving venetoclax. | |
| Participants Receiving Venetoclax + Rituximab<br>Participants with CLL receiving venetoclax in combination with rituximab. | |
| Participants Receiving Venetoclax + Obinutuzumab<br>Participants with CLL receiving venetoclax in combination with obinutuzumab. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Best Overall Response Rate (ORR) | ORR is defined as the percentage of participants achieving partial response (PR) and complete response with incomplete regeneration of bone marrow (CRi) and complete response (CR) according to physician's assessment to therapy with venetoclax. | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Still on Venetoclax Monotherapy | Percentage of participants still on venetoclax monotherapy throughout the study. | Up to 24 months | 
| Percentage of Participants Still on Venetoclax in Combination with Rituximab | Percentage of participants still on venetoclax in combination with rituximab throughout the study. | Up to 24 months | 
| Percentage of Participants Receiving Venetoclax Monotherapy with Disease Progression | Disease progression as defined in the study protocol in participants receiving venetoclax monotherapy. | Up to 24 months | 
| Percentage of Participants Receiving Venetoclax in Combination with Obinutuzumab with Disease Progression | Disease progression as defined in the study protocol in participants receiving venetoclax in combination with obinutuzumab. | Up to 24 months | 
| Percentage of Participants Receiving Venetoclax in Combination with Rituximab with Disease Progression | Disease progression as defined in the study protocol in participants receiving venetoclax in combination with rituximab. | Up to 36 months | 
| Overall Survival (OS) Rate in Participants Receiving Venetoclax Monotherapy | Percentage of participants with OS where OS is defined as the number of days from the date of entry in the study to the date of death. | Up to 24 months | 
| Overall Survival (OS) Rate in Participants Receiving Venetoclax in Combination with Obinutuzumab | Percentage of participants with OS where OS is defined as the number of days from the date of entry in the study to the date of death. | Up to 24 months | 
| Overall Survival (OS) Rate in Participants Receiving Venetoclax in Combination with Rituximab | Percentage of participants with OS where OS is defined as the number of days from the date of entry in the study to the date of death. | Up to 36 months | 
| Progression-Free Survival (PFS) Rate in Participants Receiving Venetoclax Monotherapy | Percentage of participants with PFS where PFS is defined as the number of days from the date of entry in the study to the date of the first documented disease progression, start of a subsequent treatment regimen, or death due to any cause, whichever occurs first. | Up to 24 months | 
| Progression-Free Survival (PFS) Rate in Participants Receiving Venetoclax in Combination with Obinutuzumab | Percentage of participants with PFS where PFS is defined as the number of days from the date of entry in the study to the date of the first documented disease progression, start of a subsequent treatment regimen, or death due to any cause, whichever occurs first. | Up to 24 months | 
| Progression-Free Survival (PFS) Rate in Participants Receiving Venetoclax in Combination with Rituximab | Percentage of participants with PFS where PFS is defined as the number of days from the date of entry in the study to the date of the first documented disease progression, start of a subsequent treatment regimen, or death due to any cause, whichever occurs first. | Up to 36 months | 
| Minimal Residual Disease (MRD) measurement on plasma circulating tumor Deoxyribo nucleic acid (DNA) (Switzerland Only) | MRD is defined as less than 1 clonal lymphocyte per 10000 leukocytes in peripheral blood or bone marrow. | Up to 24 months | 
| Percentage of Participants Receiving Venetoclax Monotherapy and Achieving Complete Response (CR) | Complete Response as defined in the study protocol. | Up to 24 months | 
| Percentage of Participants Receiving Venetoclax in Combination with Obinutuzumab and Achieving Complete Response (CR) | Complete Response as defined in the study protocol. | Up to 24 months | 
| Percentage of Participants Receiving Venetoclax in Combination with Rituximab and Achieving Complete Response (CR) | Complete Response as defined in the study protocol. | Up to 36 months | 
| Percentage of Participants Receiving Venetoclax Monotherapy and Achieving Complete Response with Incomplete Regeneration of Bone Marrow (CRi) | Incomplete regeneration of bone marrow (CRi) as defined in the study protocol. | Up 24 months | 
| Percentage of Participants Receiving Venetoclax Combination with Obinutuzumab and Achieving Complete Response with Incomplete Regeneration of Bone Marrow (CRi) | Incomplete regeneration of bone marrow (CRi) as defined in the study protocol. | Up 24 months | 
| Percentage of Participants Receiving Venetoclax Combination with Rituximab and Achieving Complete Response with Incomplete Regeneration of Bone Marrow (CRi) | Incomplete regeneration of bone marrow (CRi) as defined in the study protocol. | Up 36 months | 
| Percentage of Participants Receiving Venetoclax Monotherapy and Achieving Partial Response (PR) | Partial response as defined in the study protocol. | Up to 24 months | 
| Percentage of Participants Receiving Venetoclax Combination with Obinutuzumab and Achieving Partial Response (PR) | Partial response as defined in the study protocol. | Up to 24 months | 
| Percentage of Participants Receiving Venetoclax Combination with Rituximab and Achieving Partial Response (PR) | Partial response as defined in the study protocol. | Up to 36 months | 
| Percentage of Participants Receiving Venetoclax Monotherapy with Progressive Disease | Progressive disease as defined in the study protocol. | Up to 24 months | 
| Percentage of Participants Receiving Venetoclax Combination with Obinutuzumab with Progressive Disease | Progressive disease as defined in the study protocol. | Up to 24 months | 
| Percentage of Participants Receiving Venetoclax Combination with Rituximab with Progressive Disease | Progressive disease as defined in the study protocol. | Up to 36 months | 
| Percentage of Participants Receiving Venetoclax Monotherapy with Stable Disease (SD) | SD is defined as percentage of all participants not having PD, but who do not meet the criteria for PR or CR. | Up to 24 months | 
| Percentage of Participants Receiving Venetoclax Combination with Obinutuzumab with Stable Disease (SD) | SD is defined as percentage of all participants not having PD, but who do not meet the criteria for PR or CR. | Up to 24 months | 
| Percentage of Participants Receiving Venetoclax Combination with Rituximab with Stable Disease (SD) | SD is defined as percentage of all participants not having PD, but who do not meet the criteria for PR or CR. | Up to 36 months | 
| Quality of Life using EORTC QLQ-C30 Scores | European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QLQ) developed to assess the quality of life of cancer patients. and is based on multi-item and single-item scales. The core questionnaire contains 5 functional scales, 3 symptom scales, 1 global health status scale, as well as 6 single-item measures. | Up to 104 weeks | 
| QLQ-CLL 16/17 Scores | Quality of Life Questionnaire - Chronic Lymphocytic Leukemia (QLQ-CLL)16/17 is designed for participants with stage 0 to stage 4 chronic lymphocytic leukemia. It is used to assess 5 domains of health-related quality of life important in CLL: fatigue, side effects and symptoms of disease, infection and social activities or future illness-related concerns. | Up to 104 weeks | 
| European Quality of Life 5 Dimensions (EQ-5D-5L) including visual analogue scale (VAS) | The EQ-5D-5L is a standardized non-disease specific instrument for describing and valuing health-related quality of life. EQ-5D-5L questionnaire consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L questionnaire plus a VAS will be used to assess general health in 5 dimensions (mobility, self-care, usual activities, pain/discomfort anxiety/depression). | Up 24 months | 
| Management of Venetoclax Therapy | Management of venetoclax therapy includes time from blood sampling to laboratory result availability, changes in laboratory values, occurence of tumor lysis syndrome and possible interventions, length and reason for hospitalizations, duration of IV hydration, therapy modifications, supportive therapies other criteria described in the protocol. | Up to 24 Months | 
| Health Resource Utilization (HRU) per year | Health Resource Utilization (HRU) per year will be assessed. | Up to 24 Months | 
| Clonal evolution and eradication of Tumor Protein p53 (TP53) mutated clones associated with treatment in relation to MRD negativity (Switzerland Only) | Clonal evolution and eradication of TP53 mutated clones associated with treatment in relation to MRD negativity is evaluated | Up to 24 months | 
| Value of MRD Assessment | Value of MRD assessment by flow cytometry compared to comprehensive MRD assessment including flow cytometry plus NGS in peripheral blood as described in Annex II (Switzerland only). | Up to 24 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Lymphocytic Leukemia (CLL), Cancer, Leukemia, venetoclax, rituximab, obinutuzumab, ABT-199, venclexta, venclyxto