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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)

Phase 2/3
Recruiting
Conditions
Chronic Lymphocytic Leukemia
Interventions
Registration Number
2024-512147-23-00
Lead Sponsor
AbbVie Deutschland GmbH & Co. KG
Brief Summary

To evaluate the incidence of treatment-emergent laboratory TLS per Howard criteria or treatment-emergent hyperkalemia (potassium > 6.0 mmol/L), both requiring clinical intervention that has been confirmed by an Independent Review Committee (IRC) assessment in previously untreated subjects with CLL achieving either a medium tumor burden with CrCl of at least 80 mL/min or low tumor burden (regardless of CrCl level) after debulking therapy, during the venetoclax ramp-up period (5-, 6- or 7-week).

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
Not specified
Target Recruitment
115
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

Exclusion Criteria

Active/uncontrolled infection or Richter's transformation or active immune thrombocytopenia.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm D: Venetoclax + AcalabrutinibAcalabrutinibParticipants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up B.
Arm D: Venetoclax + AcalabrutinibVenetoclaxParticipants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up B.
Arm A: Venetoclax + ObinutuzumabObinutuzumabParticipants will receive venetoclax in combination with obinutuzumab, with a 5 week venetoclax ramp up.
Arm A: Venetoclax + ObinutuzumabVenetoclaxParticipants will receive venetoclax in combination with obinutuzumab, with a 5 week venetoclax ramp up.
Arm B: Venetoclax + AcalabrutinibVenetoclaxParticipants will receive venetoclax in combination with acalabrutinib, with a 5 week venetoclax ramp up.
Arm B: Venetoclax + AcalabrutinibAcalabrutinibParticipants will receive venetoclax in combination with acalabrutinib, with a 5 week venetoclax ramp up.
Arm C: Venetoclax + AcalabrutinibVenetoclaxParticipants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up A.
Arm C: Venetoclax + AcalabrutinibAcalabrutinibParticipants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up A.
Primary Outcome Measures
NameTimeMethod
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

Reduction of Tumor Burden from Baseline

Reduction of Tumor Burden from Baseline

Secondary Outcome Measures
NameTimeMethod
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: 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 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 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 Laboratory TLS per Howard criteria irrespective of clinical intervention

Part 1: Incidence of Hyperkalemia 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 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)

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

Adverse Events (AE) of TLS

Reduction of tumor burden from baseline

Reduction of tumor burden from baseline

Trial Locations

Locations (65)

Arizona Oncology - Tucson - Rudasill /ID# 267552

🇺🇸

Tucson, Arizona, United States

Southern VA Health Care System /ID# 266254

🇺🇸

Tucson, Arizona, United States

UCSF FRESNO/Community Cancer Institute /ID# 270874

🇺🇸

Clovis, California, United States

Valkyrie Clinical Trials /ID# 268151

🇺🇸

Los Angeles, California, United States

Rocky Mountain Cancer Centers - Aurora /ID# 267549

🇺🇸

Aurora, Colorado, United States

Yale University School of Medicine /ID# 266224

🇺🇸

New Haven, Connecticut, United States

Malcolm Randall V.A. Medical Center /ID# 267825

🇺🇸

Gainesville, Florida, United States

Cancer Specialists of North Florida - Jacksonville - AC Skinner Parkway /ID# 266713

🇺🇸

Jacksonville, Florida, United States

Mid Florida Hematology And Oncology Center /ID# 269159

🇺🇸

Orange City, Florida, United States

Comprehensive Hematology Oncology /ID# 267644

🇺🇸

Saint Petersburg, Florida, United States

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Arizona Oncology - Tucson - Rudasill /ID# 267552
🇺🇸Tucson, Arizona, United States
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