A Prospective, Open-Label, Phase IIb/III Study to Evaluate the Risk of TLS and Optimization of the Initiation of Venetoclax in Combination with Obinutuzumab or Acalabrutinib With Different Ramp-Up Periods in Previously Untreated Subjects with CLL
Overview
- Phase
- Phase 2/3
- Intervention
- Not specified
- Conditions
- Not specified
- Sponsor
- AbbVie Deutschland GmbH & Co. KG
- Enrollment
- 170
- Locations
- 70
- Primary Endpoint
- Reduction of Tumor Burden from Baseline
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
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.
Investigators
Global Clinical Trials Helpdesk
Scientific
AbbVie Deutschland GmbH & Co. KG
Eligibility Criteria
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 \<=
- •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.
Outcomes
Primary Outcomes
Reduction of Tumor Burden from Baseline
Reduction of Tumor Burden from Baseline
Part 1: Incidence of treatment-emergent laboratory TLS or treatment-emergent hyperkalemia per Howard criteria that require a clinical intervention that has been confirmed by an IRC assessment
Part 1: Incidence of treatment-emergent laboratory TLS or treatment-emergent hyperkalemia per Howard criteria that require a clinical intervention that has been confirmed by an IRC assessment
Secondary Outcomes
- Part 1: The incidence of treatment-emergent laboratory TLS or treatment-emergent hyperkalemia per Howard criteria that require a clinical intervention that has confirmed by an IRC assessment
- Part 1: Incidence of Laboratory TLS per Howard criteria that require a clinical intervention that has been confirmed by an IRC assessment
- Part 1: Incidence of Hyperkalemia per Howard criteria that require a clinical intervention that has been confirmed by an IRC assessment
- Part 1: Incidence of Laboratory TLS per Howard criteria irrespective of clinical intervention
- Part 1: Incidence of Hyperkalemia irrespective of clinical intervention
- Part 1: Incidence of Clinical TLS per Howard criteria irrespective of clinical intervention
- Part 1: Incidence of any single TLS-related lab abnormality requiring clinical intervention per Investigator (Hyperuricemia or Hyperphosphatemia or Hyperkalemia or Hypocalcemia)
- Adverse Events (AE) of TLS
- Reduction of tumor burden from baseline