Chronic Lymphocytic Leukemia
Conditions
Keywords
Chronic Lymphocytic Leukemia, CLL, Venetoclax, ABT-199, Obinutuzumab, Acalabrutinib
Brief summary
Chronic lymphocytic leukemia (CLL) is the most common leukemia (cancer of blood cells). The purpose of this study is to assess the safety of venetoclax in combination with obinutuzumab or acalabrutinib in the treatment of CLL. Adverse events and change in disease activity will be assessed. Venetoclax in combination with obinutuzumab or acalabrutinib is being investigated in the treatment of CLL. Study doctors put the participants in 1 of 4 groups, called treatment arms. Participants will receive oral venetoclax in combination with intravenously (IV) infused obinutuzumab or oral acalabrutinib at in different dosing schemes as part of treatment. Approximately 170 adult participants with CLL who are being treated with venetoclax will be enrolled in the study in approximately 80 sites worldwide. Participants in Arm A will receive oral venetoclax in combination with IV infused obinutuzumab, with a 5 week venetoclax ramp up. Participants in Arm B will receive oral venetoclax in combination with oral acalabrutinib, with a 5 week venetoclax ramp up. Participants in Arm C and Arm D will receive oral venetoclax in combination with oral acalabrutinib, with differing venetoclax ramp up periods. The total study duration is approximately 28 months. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Interventions
DRUGVenetoclax
Oral: Tablet
DRUGAcalabrutinib
Oral: Tablet
DRUGObinutuzumab
Intravenous Infusion
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of documented, previously untreated, chronic lymphocytic leukemia (CLL) requiring treatment according to the 2018 international workshop on chronic lymphocytic leukemia (iwCLL) criteria and have a life expectancy of \> 6 months. * Previously untreated small lymphocytic lymphoma (SLL) meeting the 2018 iwCLL criteria for treatment will also be equally considered as CLL for eligibility, screening, treatment and evaluation. * Eastern Cooperative Oncology Group (ECOG) performance status \<= 2. * Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening, unless cytopenia is due to marrow involvement of CLL as listed in the protocol. * Creatinine clearance (CrCl) \>= 30 mL/min using the Cockcroft-Gault formula are eligible for inclusion.
Exclusion criteria
\- Active/uncontrolled infection, no Richter's transformation, no active immune thrombocytopenia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Participants with Treatment-Emergent Laboratory Tumor Lysis Syndrome (TLS)-Venetoclax | Up to 28 Months | TLS is defined per Howard criteria that require a clinical intervention per independent review committee (IRC) assessment during the venetoclax ramp-up period in previously untreated participants with chronic lymphocytic leukemia (CLL) achieving a medium tumor burden with creatinine clearance (CrCl) of at least 80 ml/min or low tumor burden (regardless of CrCl level) after debulking therapy. |
| Part 1: Percentage of Participants with Hyperkalemia-Venetoclax | Up to 28 Months | Hyperkalemia (potassium \>6.0 mmol/L) is defined per Howard criteria that require a clinical intervention per IRC assessment during the venetoclax ramp-up period in previously untreated participants with CLL achieving a medium tumor burden with CrCl of at least 80 ml/min or low tumor burden (regardless of CrCl level) after debulking therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Participants with Treatment-Emergent Laboratory TLS | Up to 28 Months | TLS is defined per Howard criteria that require a clinical intervention per IRC assessment, at each dose level and at each laboratory monitoring point during ramp-up period in previously untreated participants with CLL achieving a medium tumor burden with CrCl of at least 80 ml/min or low tumor burden (regardless of CrCl level) after debulking therapy. |
| Part 1: Percentage of Participants with Hyperkalemia | Up to 28 Months | Hyperkalemia (potassium \>6.0 mmol/L) is defined per Howard criteria that require a clinical intervention per independent review committee (IRC) assessment during the venetoclax ramp-up period in previously untreated participants with CLL achieving a medium tumor burden with CrCl of at least 80 ml/min or low tumor burden (regardless of CrCl level) after debulking therapy. |
| Part 1: Percentage of Participants with Treatment-Emergent TLS-Related Events | Up to 28 Months | TLS-related events are defined as laboratory TLS per Howard criteria requiring clinical intervention per IRC assessment, hyperkalemia (potassium \>6.0 mmol/L) requiring clinical intervention per IRC assessment, laboratory TLS per Howard criteria irrespective of clinical intervention, Hyperkalemia (potassium \>6.0 mmol/L) irrespective of clinical intervention, clinical TLS per Howard criteria irrespective of clinical intervention, any single TLS-related lab abnormality requiring clinical intervention per Investigator. |
| Part 1: Percentage of Participants with Adverse Events (AE) of TLS | Up to 28 Months | AEs of TLS is defined as a blood chemistry changes or symptom suggestive of TLS. |
| Part 1: Percentage of Participants with Reduction of Tumor Burden from Baseline | Up to 28 Months | Percentage of participants with reduction of tumor burden. |
Countries
Australia, France, Greece, Puerto Rico, Serbia, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTABBVIE CALL CENTER
STUDY_DIRECTORABBVIE INC.
AbbVie
Outcome results
None listed