Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL (AMPLIFY)

Acerta Pharma

Status and phase: Active, not recruiting; Phase 3

Conditions: Chronic Lymphocytic Leukemia

Treatments: Drug: Venetoclax; Drug: Obinutuzumab; Drug: Chemoimmunotherapy; Drug: Acalabrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03836261

ACE-CL-311

2018-002443-28 (EudraCT Number)

D8221C00001 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of acalabrutinib in combination with venetoclax and acalabrutinib in combination with venetoclax with and without obinutuzumab compared to chemoimmunotherapy in subjects with previously untreated CLL

Full description

This randomized, global, multicenter, open-label, Phase 3 study will evaluate the efficacy and safety of AV and AVG versus chemoimmunotherapy (FCR or BR) in subjects with previously untreated CLL without del(17p) or TP53. Subjects will be randomized in a 1:1:1 ratio into 3 arms through a block stratified randomization procedure.

The study includes screening (35 days), treatment (from randomization until study drug discontinuation) and follow-up phase.

Enrollment: 984 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Men and women ≥18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Diagnosis of CLL that meets published diagnostic criteria (Hallek et al. 2018)
• Active disease per IWCLL 2018 criteria that requires treatment.
• Participants must use highly effective birth control throughout the study.

Exclusion criteria

• Any prior CLL-specific therapies.
• Detected del(17p) or TP53 mutation.
• Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (e.g., Richter's transformation, prolymphocytic leukemia [PLL], or diffuse large B cell lymphoma [DLBCL]), or central nervous system (CNS) involvement by leukemia.
• History of confirmed progressive multifocal leukoencephalopathy (PML).
• Received any investigational drug within 30 days before first dose of study drug.
• Major surgical procedure within 30 days before the first dose of study drug.
• Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 or 4 cardiac disease. Note: Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach, or extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
• Received a live virus vaccination within 28 days of first dose of study drug.
• Known history of infection with human immunodeficiency virus (HIV).
• Serologic status reflecting active hepatitis B or C infection.
• History of known hypersensitivity or anaphylactic reactions to study drugs or excipients.
• History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
• Known bleeding disorders.
• Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
• Female participants must not be breastfeeding or pregnant.
• Concurrent participation in another therapeutic clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

984 participants in 3 patient groups

Acalabrutinib, Venetoclax

Experimental group

Description:

Acalabrutinib in combination with Venetoclax

Treatment:

Drug: Acalabrutinib

Drug: Venetoclax

Acalabrutinib, Venetoclax, Obinutuzumab

Experimental group

Description:

Acalabrutinib in combination with Venetoclax with Obinutuzumab

Treatment:

Drug: Acalabrutinib

Drug: Obinutuzumab

Drug: Venetoclax

Chemoimmunotherapy

Active Comparator group

Description:

Chemoimmunotherapy FCR: Fludarabine, Cyclophosphamide and Rituximab BR: Bendamustine and Rituximab

Treatment:

Drug: Chemoimmunotherapy