Clinical trial NCT06697184: A Study to Investigate the Safety of Novel Dose Ramp-up Schedule(s) When Initiating Sonrotoclax in Participants Treated for Blood Cancers.
Official title: A Phase 1/2 Open-label Study to Investigate the Safety of Sonrotoclax Ramp-up Schedule(s) in Adult Patients With Hematological Malignancies.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Chronic Lymphocytic Leukemia
CLL
Keywords: CLL previously untreated
Hematological Malignancies
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-11-20
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to establish the safety of novel dosing and ramp-up schedules for sonrotoclax in participants with hematological malignancies.

Detailed description: This study will test the safety of novel sonrotoclax dosing with gradual increases of sonrotoclax dose over specified periods until the intended target daily dose is reached. The focus will be on tumor lysis syndrome (TLS) and related toxicity signals.

In the first part of the study, each ramp-up dosing schedule will first be tested in a small group of approximately 5 to 6 participants to assess safety and establish if the schedule is suitable for further testing in additional participants (schedule calibration). In the second part of the study, approved ramp-up schedules will be further assessed for safety in approximately 50 participants (schedule expansion).

Sonrotoclax is an experimental drug that works by blocking a protein called B-cell lymphoma-2 (BCL-2). This protein helps certain types of blood tumor cells to survive and grow. When sonrotoclax blocks Bcl-2 it slows down or stops the growth of tumor cells and helps them die. This can lead to improvements in patients with certain malignant diseases including Chronic Lymphocytic leukemia (CLL). The start of treatment by BCL2 inhibitor requires progressive ramp-up over the first weeks to avoid potential consequences of initial tumor cell breakage and the release of cell content in the bloodstream. Several ramp-up schedules have already been utilized so far, and this study aims to optimize the dosing schedule by evaluating novel ones as safe, while simpler and/or faster.

Zanubrutinib is a commercialized product that works by blocking a protein called Bruton's tyrosine kinase (BTK) and controlling the activity and survival of malignant B cells. Zanubrutinib has received approval in over 65 countries/regions worldwide for the treatment of adult participants with B cell malignancies, including CLL.

This study will take place at multiple centers worldwide. The overall time to participate in this study is approximately 17 months.

Eligibility criteria: Inclusion Criteria:

1. Stable ECOG Performance Status ≤ 2.
2. Adequate organ function and no very recent transfusion or blood growth factor
3. Participants of childbearing potential must be willing to use a highly effective method of birth control and refrain from egg donation for the duration of the study and for ≥ 90 days after the last dose of sonrotoclax or ≥ 30 days after the last dose of zanubrutinib, whichever is later.
4. Confirmed diagnosis of CLL, based on Hallek et al 2018, and requiring treatment due to certain features of their disease
5. At least 1 measurable lesion based on computed tomography (CT)/magnetic resonance imaging (MRI) and no history of prolymphocytic leukemia or Richter's transformation.

Exclusion Criteria:

1. Participants unable to comply with the requirements of the protocol
2. Serologic status reflecting active viral HBV or HCV infection
3. Positive HIV serology (HIVAb) status unless certain conditions are met.
4. Participants with any major surgical procedure ≤ 28 days before first dose of study treatment
5. Prior systemic treatment for the CLL
6. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring treatment

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Number of Participants who Experience Tumor Lysis Syndrome (TLS)
timeFrame: Approximately 4 months
Secondary outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Approximately 4 months
measure: Number of Participants with Dose Modifications During the SLT Evaluation Window
timeFrame: Approximately 4 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Blacktown
country: Australia
facility: Blacktown Cancer and Haematology Centre
state: New South Wales
city: Malvern East
country: Australia
facility: Cabrini Hospital Malvern
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Cooloongup
country: Australia
facility: Rockingham Hospital
state: Western Australia
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Bobigny
country: France
facility: Hopital Avicenne, Aphp, Bobigny
city: Dijon
country: France
facility: Chu Dijon
city: Montpellier
country: France
facility: Chu Montpellier Hopital Saint Eloi
city: Nice
country: France
facility: Hopital Larchet Chu Nice
city: Toulouse
country: France
facility: Iuct Oncopole
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Leeds
country: United Kingdom
facility: St Jamess University Hospital
city: Manchester
country: United Kingdom
facility: The Christie Nhs Foundation Trust Manchester
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: