## Protocol Section
### Identification Module
**NCT ID:** NCT06428019

**Brief Title:** 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)

**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

#### Organization Study ID Info
**ID:** M24-287
#### Organization
**Class:** INDUSTRY
**Full Name:** AbbVie
#### Secondary ID Infos
**Domain:** EU CT
**ID:** 2024-512147-23-00
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2026-10-21

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-20

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-10-21

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-06

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-20
**Study First Submit QC Date:** 2024-05-20
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** AbbVie

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** True

**Oversight Has DMC:** False

### Description Module

**Brief 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.

### Conditions Module

**Conditions:**

- Chronic Lymphocytic Leukemia

**Keywords:**

- Chronic Lymphocytic Leukemia

- CLL

- Venetoclax

- ABT-199

- Obinutuzumab

- Acalabrutinib

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 120

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

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

**Intervention Names:**

- Drug: Venetoclax

- Drug: Obinutuzumab

**Label:** Arm A: Venetoclax + Obinutuzumab

**Type:** EXPERIMENTAL

#### Arm Group 2

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

**Intervention Names:**

- Drug: Venetoclax

- Drug: Acalabrutinib

**Label:** Arm B: Venetoclax + Acalabrutinib

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** Participants will receive venetoclax in combination with acalabrutinib, with a 6 week venetoclax ramp up.

**Intervention Names:**

- Drug: Venetoclax

- Drug: Acalabrutinib

**Label:** Arm C: Venetoclax + Acalabrutinib

**Type:** EXPERIMENTAL

#### Arm Group 4

**Description:** Participants will receive venetoclax in combination with acalabrutinib, with a 7 week venetoclax ramp up.

**Intervention Names:**

- Drug: Venetoclax

- Drug: Acalabrutinib

**Label:** Arm D: Venetoclax + Acalabrutinib

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Arm A: Venetoclax + Obinutuzumab

- Arm B: Venetoclax + Acalabrutinib

- Arm C: Venetoclax + Acalabrutinib

- Arm D: Venetoclax + Acalabrutinib

**Description:** Oral: Tablet

**Name:** Venetoclax

**Other Names:**

- ABT-199

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Arm B: Venetoclax + Acalabrutinib

- Arm C: Venetoclax + Acalabrutinib

- Arm D: Venetoclax + Acalabrutinib

**Description:** Oral: Tablet

**Name:** Acalabrutinib

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Arm A: Venetoclax + Obinutuzumab

**Description:** Intravenous Infusion

**Name:** Obinutuzumab

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

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

**Time Frame:** Up to 28 Months

**Description:** 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.

**Measure:** Part 1: Percentage of Participants with Hyperkalemia-Venetoclax

**Time Frame:** Up to 28 Months

#### Secondary Outcomes

**Description:** 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.

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

**Time Frame:** Up to 28 Months

**Description:** 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.

**Measure:** Part 1: Percentage of Participants with Hyperkalemia

**Time Frame:** Up to 28 Months

**Description:** 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.

**Measure:** Part 1: Percentage of Participants with TLS-Related Events

**Time Frame:** Up to 28 Months

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

**Measure:** Part 1: Percentage of Participants with Adverse Events (AE) of TLS

**Time Frame:** Up to 28 Months

**Description:** Percentage of participants with reduction of tumor burden.

**Measure:** Part 1: Percentage of Participants with Reduction of Tumor Burden from Baseline

**Time Frame:** Up to 28 Months

### Eligibility Module

**Eligibility Criteria:** 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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** abbvieclinicaltrials@abbvie.com

**Name:** ABBVIE CALL CENTER

**Phone:** 844-663-3742

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** AbbVie

**Name:** ABBVIE INC.

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**Access Criteria:** Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/

**Description:** AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

**Info Types:**

- STUDY_PROTOCOL

- SAP

- CSR

**IPD Sharing:** YES

**Time Frame:** For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/

**URL:** https://vivli.org/ourmember/abbvie/

### References Module

#### See Also Links

**Label:** Related Info

**URL:** https://www.abbvieclinicaltrials.com/study/?id=M24-287

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000008232

- Term: Lymphoproliferative Disorders

- ID: D000008206

- Term: Lymphatic Diseases

- ID: D000007160

- Term: Immunoproliferative Disorders

- ID: D000007154

- Term: Immune System Diseases

- ID: D000015448

- Term: Leukemia, B-Cell

- ID: D000002908

- Term: Chronic Disease

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M10945

- Name: Leukemia

- Relevance: HIGH

- As Found: Leukemia

- ID: M10951

- Name: Leukemia, Lymphoid

- Relevance: HIGH

- As Found: Lymphocytic Leukemia

- ID: M18116

- Name: Leukemia, Lymphocytic, Chronic, B-Cell

- Relevance: HIGH

- As Found: Chronic Lymphocytic Leukemia

- ID: M17975

- Name: Tumor Lysis Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11225

- Name: Lymphoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M11203

- Name: Lymphatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10206

- Name: Immunoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M18115

- Name: Leukemia, B-Cell

- Relevance: LOW

- As Found: Unknown

- ID: M6147

- Name: Chronic Disease

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

- ID: T1308

- Name: Chronic Lymphocytic Leukemia

- Relevance: HIGH

- As Found: Chronic Lymphocytic Leukemia

### Condition Browse Module - Meshes

- ID: D000007938

- Term: Leukemia

- ID: D000007945

- Term: Leukemia, Lymphoid

- ID: D000015451

- Term: Leukemia, Lymphocytic, Chronic, B-Cell

### Intervention Browse Module - Ancestors

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000074322

- Term: Antineoplastic Agents, Immunological

- ID: D000092004

- Term: Tyrosine Kinase Inhibitors

- ID: D000047428

- Term: Protein Kinase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: AA

- Name: Amino Acids

### Intervention Browse Module - Browse Leaves

- ID: M249656

- Name: Venetoclax

- Relevance: HIGH

- As Found: Extended

- ID: M288906

- Name: Obinutuzumab

- Relevance: HIGH

- As Found: Contraction

- ID: M42185

- Name: Acalabrutinib

- Relevance: HIGH

- As Found: Vinorelbine

- ID: M1346

- Name: Antineoplastic Agents, Immunological

- Relevance: LOW

- As Found: Unknown

- ID: M2889

- Name: Tyrosine Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M25820

- Name: Protein Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: T22

- Name: Tyrosine

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000579720

- Term: Venetoclax

- ID: C000543332

- Term: Obinutuzumab

- ID: C000604908

- Term: Acalabrutinib

### Misc Info Module

- Version Holder: 2024-05-31
