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)

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06428019
• Other study ID #: M24-287
• Secondary ID: 2024-512147-23-0
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 6, 2024
• Est. completion date: October 21, 2026

Study information

• Verified date: May 2024
• Source: AbbVie
• Contact: ABBVIE CALL CENTER
• Phone: 844-663-3742
• Email: abbvieclinicaltrials[@]abbvie.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: October 21, 2026
• Est. primary completion date: October 21, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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, while individuals with lymph nodes > 5 cm and CrCl < 80 mL/min are excluded.

Exclusion Criteria:

• Active/uncontrolled infection, no Richter's transformation, no active immune thrombocytopenia.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Venetoclax
Oral: Tablet
• Acalabrutinib
Oral: Tablet
• Obinutuzumab
Intravenous Infusion

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Percentage of Participants with Treatment-Emergent Laboratory Tumor Lysis Syndrome (TLS)-Venetoclax	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.	Up to 28 Months
Primary	Part 1: Percentage of Participants with Hyperkalemia-Venetoclax	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.	Up to 28 Months
Secondary	Part 1: Percentage of Participants with Treatment-Emergent Laboratory TLS	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.	Up to 28 Months
Secondary	Part 1: Percentage of Participants with Hyperkalemia	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.	Up to 28 Months
Secondary	Part 1: Percentage of Participants with TLS-Related Events	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.	Up to 28 Months
Secondary	Part 1: Percentage of Participants with Adverse Events (AE) of TLS	AEs of TLS is defined as a blood chemistry changes or symptom suggestive of TLS.	Up to 28 Months
Secondary	Part 1: Percentage of Participants with Reduction of Tumor Burden from Baseline	Percentage of participants with reduction of tumor burden.	Up to 28 Months

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