A Study to Evaluate the Risk of Tumor Lysis Syndrome (TLS) in Adult Participants Receiving Oral Venetoclax in Combination With Intravenously Infused Obinutuzumab or Oral Acalabrutinib for Previously Untreated Chronic Lymphocytic Leukemia (CLL)

AbbVie

Status and phase: Enrolling; Phase 3

Conditions: Chronic Lymphocytic Leukemia

Treatments: Drug: Acalabrutinib; Drug: Obinutuzumab; Drug: Venetoclax

Study type: Interventional

Funder types: Industry

Identifiers

NCT06428019

2024-512147-23-00 (Other Identifier)

M24-287

Details and patient eligibility

About

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 120 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

120 participants in 4 patient groups

Arm A: Venetoclax + Obinutuzumab

Experimental group

Description:

Participants will receive venetoclax in combination with obinutuzumab, with a 5 week venetoclax ramp up.

Treatment:

Drug: Venetoclax

Drug: Obinutuzumab

Arm B: Venetoclax + Acalabrutinib

Experimental group

Description:

Participants will receive venetoclax in combination with acalabrutinib, with a 5 week venetoclax ramp up.

Treatment:

Drug: Venetoclax

Drug: Acalabrutinib

Arm C: Venetoclax + Acalabrutinib

Experimental group

Description:

Participants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up A.

Treatment:

Drug: Venetoclax

Drug: Acalabrutinib

Arm D: Venetoclax + Acalabrutinib

Experimental group

Description:

Participants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up B.

Treatment:

Drug: Venetoclax

Drug: Acalabrutinib