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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

21 Nov 2024 → ongoing

Decision date (initial)

2024-10-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Inc.

External identifiers

EU CT number

2024-512147-23-00

ClinicalTrials.gov

NCT06428019

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic

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).

Secondary objectives 4

1. To evaluate the incidence of treatment-emergent laboratory TLS per Howard criteria or treatment-emergent hyperkalemia, requiring clinical intervention that has been confirmed by an 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 at each dose level and at each laboratory monitoring point during the ramp-up period
2. To assess the incidence of the treatment-emergent TLS-related events detailed below (overall, at each dose level and at each laboratory monitoring point during the ramp-up period) in previously untreated subjects 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: 1. Laboratory TLS per Howard criteria requiring clinical intervention that has been confirmed by an IRC assessment. 2. Hyperkalemia requiring clinical intervention that has been confirmed by an IRC assessment. 3. Laboratory TLS per Howard criteria irrespective of clinical intervention. 4. Hyperkalemia irrespective of clinical intervention. 5. Clinical TLS per Howard criteria irrespective of clinical intervention. 6. One of the following lab abnormalities requiring clinical intervention per Investigator: a. Hyperuricemia b. Hyperphosphatemia c. Hyperkalemia d. Hypocalcemia
3. To assess AEs of TLS as reported by the Investigator during the venetoclax ramp-up period 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.
4. To evaluate reduction of tumor burden from baseline to after debulking in all enrolled subjects who have TLS assessments performed at both baseline and after debulking.

Conditions and MedDRA coding

Chronic Lymphocytic Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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.
2. 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.
3. Eastern Cooperative Oncology Group (ECOG) performance status <= 2.
4. 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.
5. Creatinine clearance (CrCl) >= 30 mL/min using the Cockcroft-Gault formula

Exclusion criteria 1

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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
2. Reduction of Tumor Burden from Baseline

Secondary endpoints 9

1. 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
2. Part 1: Incidence of Laboratory TLS per Howard criteria that require a clinical intervention that has been confirmed by an IRC assessment
3. Part 1: Incidence of Hyperkalemia per Howard criteria that require a clinical intervention that has been confirmed by an IRC assessment
4. Part 1: Incidence of Laboratory TLS per Howard criteria irrespective of clinical intervention
5. Part 1: Incidence of Hyperkalemia irrespective of clinical intervention
6. Part 1: Incidence of Clinical TLS per Howard criteria irrespective of clinical intervention
7. Part 1: Incidence of any single TLS-related lab abnormality requiring clinical intervention per Investigator (Hyperuricemia or Hyperphosphatemia or Hyperkalemia or Hypocalcemia)
8. Adverse Events (AE) of TLS
9. Reduction of tumor burden from baseline

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation

AbbVie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 2

Locations

3 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications