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NCT Number: NCT06428019

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 (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.

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Key information

Conditions

Chronic Lymphocytic Leukemia Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Calvary Mater Newcastle /ID# 267408, Waratah, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Venetoclax

Drug

Oral: Tablet

Other names: ABT-199

Acalabrutinib

Drug

Oral: Tablet

Obinutuzumab

Drug

Intravenous Infusion

Primary outcomes

  1. Part 1: Percentage of Participants with Treatment-Emergent Laboratory Tumor Lysis Syndrome (TLS)-Venetoclax

    Time frame: 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.

  2. Part 1: Percentage of Participants with Hyperkalemia-Venetoclax

    Time frame: 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 outcomes

  1. Part 1: Percentage of Participants with Treatment-Emergent Laboratory TLS

    Time frame: 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.

  2. Part 1: Percentage of Participants with Hyperkalemia

    Time frame: 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.

  3. Part 1: Percentage of Participants with Treatment-Emergent TLS-Related Events

    Time frame: 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.

  4. Part 1: Percentage of Participants with Adverse Events (AE) of TLS

    Time frame: Up to 28 Months

    AEs of TLS is defined as a blood chemistry changes or symptom suggestive of TLS.

  5. Part 1: Percentage of Participants with Reduction of Tumor Burden from Baseline

    Time frame: Up to 28 Months

    Percentage of participants with reduction of tumor burden.

Study contacts

Contact information is provided by the study sponsor or research team.

ABBVIE CALL CENTER

CONTACT

[email protected]

844-663-3742

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Registry information

Official study 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

Important dates

Study start
2024
Primary completion
2028
Study completion
2028
First posted
May 24, 2024
Registry last updated
Apr 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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