AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia

B-cell Acute Lymphoblastic Leukemia (B-ALL) Clinical Trial

Official title:

A Phase 1/2 Study to Evaluate the Safety and Efficacy of AZD0486 in Adolescent and Adult Participants With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukaemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06137118
• Other study ID #: D7405C00001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 29, 2023
• Est. completion date: February 4, 2027

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1/2, global multicentre, open-label, single-arm, dose escalation and dose optimisation study of AZD0486 to evaluate the safety, tolerability, and efficacy of AZD0486 monotherapy in participants with R/R B ALL who have received ≥ 2 prior lines of therapies. The study will consist of 3 parts. Part A monotherapy dose escalation. Part B dose optimisation. Part C Dose expansion at the recommended phase 2 dose (RP2D)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: February 4, 2027
• Est. primary completion date: January 29, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age: 16 years and older (Part A), 12 years and older (Parts B and C).
• Participants with CD19+ B-cell Acute Lymphoblastic Leukemia by local lab with:

1. Bone marrow infiltration with >/= 5% blasts

2. Either relapsed or refractory after a minimum of 2 prior therapies or after 1 prior line of therapy if no SOC available option.

3. Philadelphia positive participants are allowed in Part A if intolerant or refractory to TKIs.

• Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2 OR Lansky score more or equal to 50%. The above is a summary, other inclusion criteria details may apply.

Exclusion Criteria:

• Active CNS involvement by B-ALL, defined by presence of ALL blasts in CSF (CNS2 and CNS3 criteria).
• Isolated extramedullary disease relapse.
• Testicular leukemia
• History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis; or prior Grade 4 neurotoxicity with CAR-T or TCE therapy.
• History of other malignancy (with certain exceptions).
• Unresolved AEs >/= Grade 2, from prior therapies
• Prior therapy with TCEs within 4 weeks, CAR T-cell therapy or autologous HSCT within 8 weeks or prior alloSCT within 12 weeks of start of therapy.
• GVHD requiring immunosuppressive therapy within 3 weeks prior to AZD0486 treatment. The above is a summary, other exclusion criteria details may apply.

Related Conditions & MeSH terms

• B-cell Acute Lymphoblastic Leukemia (B-ALL)
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• AZD0486
Investigational Product administered via intravenous infusion.

Locations

Country	Name	City	State
Australia	Research Site	Melbourne
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Suzhou
China	Research Site	Zhengzhou
France	Research Site	Marseille
France	Research Site	Nantes
France	Research Site	Paris
France	Research Site	Pierre Bénite
Germany	Research Site	Essen
Germany	Research Site	Frankfurt A. Main
Germany	Research Site	Freiburg
Germany	Research Site	Halle
Germany	Research Site	Hamburg
Germany	Research Site	Köln
Germany	Research Site	Muenchen
Germany	Research Site	Münster
Germany	Research Site	Würzburg
Italy	Research Site	Bologna
Italy	Research Site	Monza
Italy	Research Site	Roma
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Valencia
Taiwan	Research Site	Kaohsiung City
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United States	Research Site	Birmingham	Alabama
United States	Research Site	Chicago	Illinois
United States	Research Site	Duarte	California
United States	Research Site	Houston	Texas
United States	Research Site	Los Angeles	California
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	New York	New York
United States	Research Site	Palo Alto	California
United States	Research Site	Richmond	Virginia
United States	Research Site	Seattle	Washington
United States	Research Site	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  France,  Germany,  Italy,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Frequency of DLTs	DLTs are dose-limiting toxicities as defined in the study protocol	28 days
Primary	Parts A, B, C: Safety Evaluation of AZD0486	Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in physical examination and safety procedures.	From signing of informed consent through study completion, an average of 8 months
Primary	Parts B & C: Overall Response Rate (ORR)	The Primary analysis for ORR be conducted in RP2D-treated participants (in Part B and C).	From First dose to end of treatment or data cutoff, whichever comes first, assessed up to 24 months
Secondary	Part A: Objective Response Rate (ORR)	Overall response rate (ORR) in the evaluable participant set, defined as proportion of participants who achieve overall response (CR/CRi).	From First dose to end of treatment or data cutoff, whichever comes first, assessed up to 12 months
Secondary	Parts A, B, C: Duration of response (DoR)	Date of first documented CR/CRi until the date of relapse or death	Up to 36 months
Secondary	Parts A, B, C: CR rate at any time during the study	CR rate as defined as the percentage of participants achieving CR at any time by NCCN criteria	From first dose until end of study, up to 36 months
Secondary	Parts A, B, C: Event-free survival (EFS)	Event-free survival is defined as the time from the date of the first dose until the date of a relapse after achieving a CR/ CRi, or death due to any cause.	From first dose until end of study, up to 36 months
Secondary	Parts A, B, C: Overall survival (OS)	OS measured from first dose of study drug until death	From first dose until end of study, up to 36 months
Secondary	Parts B & C: Subsequent alloSCT	Number of patients who after achieve CR/CR underwent an alloSCT	From first dose until end of study, up to 24 months
Secondary	Parts B &C: CR MRD-negative rate	Number of patients who achieve CR MRD-negative by NGS at any time on study	First dose until end of study, up to 24 months
Secondary	Parts A, B, & C: PK characterization of AZD0486	Derived PK parameter: AUC	From first dose until end of study, up to 36 months
Secondary	Parts A, B & C: PK Characterization of AZD0486	Derived PK parameter: Cmax	From first dose until end of study, up to 36 months
Secondary	Parts A, B, C: PK Characterization of AZD0486	Derived PK Parameter: tmax	From first dose until end of study, up to 36 months
Secondary	Parts A, B, C: PK Characterization of AZD0486	Derived PK parameter: Ctrough	From first dose until end of study, up to 36 months
Secondary	Parts A, B, C: PK Characterization of AZD0486	Derived PK Parameter: t1/2	Pre-defined intervals from day 1 to day 28
Secondary	Parts A, B, C: PK Characterization of AZD0486	Derived PK Parameter: CL of AZD0486	From first dose until end of study, up to 36 months
Secondary	Parts A, B, C: ADA characterization of AZD0486	Number of participants who develop ADA during study.	First dose up to 36 months