The purpose of this study is to assess the safety and efficacy of AZD0486 administered as monotherapy or in combination with other anticancer agents in participants with hematological malignancies.
This is open-label, multi-center study to evaluate the safety and preliminary efficacy of AZD0486 administered as monotherapy and in combination with other anticancer agents in participants with mature B-cell hematologic malignancies. This master study currently includes 3 substudies and each substudy focusing on a defined population: Substudy 1: Relapsed/refractory (R/R) Chronic lymphocytic leukaemia (CLL)/ Small lymphocytic lymphoma (SLL) Substudy 2: R/R Mantle-cell lymphoma (MCL) Substudy 3: Large B-cell lymphoma (LBCL) or R/R B-cell non-Hodgkin lymphoma (B-NHL) (not applicable to US) The study will have the following sequential periods: 1. Screening period of 28 days 2. Treatment period 3. Follow-up period
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
276
Number of Participants with Adverse Events, Serious Adverse Events and Adverse Events of Special Interest
Safety and tolerability of AZD0486 as monotherapy and in combination with other anticancer agents across mature B-cell malignancies.
Time frame: Up to 6 years 4 months
Number of Participants with Dose Limiting Toxicity (DLTs)
Safety and tolerability of AZD0486 as monotherapy and in combination with other anticancer agents across mature B-cell malignancies.
Time frame: Up to 2 months
Objective Response Rate (ORR)
ORR is defined as percentage of participants achieving either a partial response (PR) or complete response (CR) based on response criteria for International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 and Lugano 2014 assessed by investigator (substudy 1) and percentage of participants achieving CR as best response based on Lugano 2014 Response Criteria by investigator assessment (substudies 2 and 3).
Time frame: Up to 6 years 4 months
Complete Response (CR) Rate
CR rate is defined as percentage of participants achieving CR as best response based on response criteria for iwCLL 2018 and Lugano 2014 assessed by investigator (substudy 1) and percentage of participants achieving CR as best response based on Lugano 2014 Response Criteria by investigator assessment (substudies 2 and 3).
Time frame: Up to 6 years 4 months
Duration of Response (DoR)
DoR is defined as time from the date of first documented response until date of documented progression based on response criteria for iwCLL 2018 and Lugano 2014 assessed by investigator, relapse or death (substudy 1) and time from the date of first documented response until date of documented progression based on Lugano 2014 Response Criteria by investigator assessment, relapse or death (substudies 2 and 3).
AstraZeneca Clinical Study Information Center
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Cyclophosphamide will be administered as IV infusion as per standard of care.
Vincristine will be administered as IV infusion as per standard of care.
Doxorubicin will be administered as IV infusion as per standard of care.
Acalabrutinib will be administered orally
Research Site
Boston, Massachusetts, United States
RECRUITINGResearch Site
Hackensack, New Jersey, United States
NOT_YET_RECRUITINGResearch Site
New Brunswick, New Jersey, United States
RECRUITINGResearch Site
New York, New York, United States
RECRUITINGResearch Site
New York, New York, United States
NOT_YET_RECRUITINGResearch Site
Charlotte, North Carolina, United States
RECRUITINGResearch Site
Charlotte, North Carolina, United States
NOT_YET_RECRUITINGResearch Site
Columbus, Ohio, United States
NOT_YET_RECRUITINGResearch Site
Portland, Oregon, United States
RECRUITINGResearch Site
Philadelphia, Pennsylvania, United States
RECRUITING...and 53 more locations
Time frame: Up to 6 years 4 months
Maximum Observed Concentration (Cmax)
The PK (Cmax) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated.
Time frame: Up to 90 days after last dose
Area Under the Concentration-time Curve (AUC)
The PK (AUC) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated.
Time frame: Up to 90 days after last dose
Minimum Observed Concentration (Cmin)
The PK (Cmin) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated.
Time frame: Up to 90 days after last dose
Time to Reach Maximum Concentration (Tmax)
The PK (Tmax) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated.
Time frame: Up to 90 days after last dose
Trough Plasma Concentration (Ctrough)
The PK (Ctrough) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated.
Time frame: Up to 90 days after last dose
Half Life (t1/2) of AZD0486
The PK (t1/2) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated.
Time frame: Up to 90 days after last dose
Clearance (CL) of AZD0486
The PK (CL) of AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated.
Time frame: Up to 90 days after last dose
Number of Participants with Anti-drug Antibody (ADA) for AZD0486
The incidence of immunogenicity of SC AZD0486 as monotherapy and in combination with other anti-cancer agents will be evaluated.
Time frame: Up to 90 days after last dose