Clinical trial NCT06137118: AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-cell Acute Lymphoblastic Leukemia (B-ALL)
Keywords: B-cell acute lymphoblastic leukemia
Leukemia
B-lymphocytes
AZD0486
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-11-18
Enrollment: 120
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The trial will assess AZD0486 IV infusion in monotherapy. Part A will evaluate ascending dose levels of AZD0486 in participants 12 years and above with B-ALL. Part B will evaluate up to 2 safe-declared dose levels in participants with Ph(-) B-ALL aged 12 years and above to select the RP2D. Part C will expand the RP2D dose level cohort to assess efficacy in a large number of subjects.
Primary purpose: TREATMENT

Brief 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)

Detailed description: This dose escalation and optimization study is evaluating the safety, tolerability, PK, PD and clinical activity of AZD0486 monotherapy in r/r B-ALL.

Eligibility criteria: Inclusion Criteria:

* Age: 12 years and above (Parts A, B and C).
* Participants with B-cell Acute Lymphoblastic Leukemia with CD19 expression 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.
* For participants older than 16 years, Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2. For Participants 16 years or younger, 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.

Primary outcomes:
measure: Part A: Frequency of DLTs
timeFrame: 28 days
measure: Parts A & B: Safety Evaluation of AZD0486
timeFrame: From signing of informed consent through completion of study treatment, an average of 6 months
measure: Parts B & C: Overall Response Rate (ORR)
timeFrame: From First dose to end of treatment or data cutoff, whichever comes first, assessed up to 24 months
Secondary outcomes:
measure: Part A: Objective Response Rate (ORR)
timeFrame: From First dose to end of treatment or data cutoff, whichever comes first, assessed up to 12 months
measure: Parts A, B, C: Duration of response (DoR)
timeFrame: Up to 36 months
measure: Parts A, B, C: CR rate at any time during the study
timeFrame: From first dose until end of study, up to 36 months
measure: Parts A, B, C: Event-free survival (EFS)
timeFrame: From first dose until end of study, up to 36 months
measure: Parts A, B, C: Overall survival (OS)
timeFrame: From first dose until end of study, up to 36 months
measure: Parts B & C: Subsequent alloSCT or Donor Lymphocyte Infusion
timeFrame: From first dose until end of study, up to 24 months
measure: Parts B &C: CR MRD-negative rate
timeFrame: First dose until end of study, up to 24 months
measure: Parts A, B, & C: PK characterization of AZD0486
timeFrame: From first dose until end of study, up to 36 months
measure: Parts A, B & C: PK Characterization of AZD0486
timeFrame: From first dose until end of study, up to 36 months
measure: Parts A, B, C: PK Characterization of AZD0486
timeFrame: From first dose until end of study, up to 36 months
measure: Parts A, B, C: PK Characterization of AZD0486
timeFrame: From first dose until end of study, up to 36 months
measure: Parts A, B, C: PK Characterization of AZD0486
timeFrame: Pre-defined intervals from day 1 to day 28
measure: Parts A, B, C: PK Characterization of AZD0486
timeFrame: From first dose until end of study, up to 36 months
measure: Parts A, B, C: ADA characterization of AZD0486
timeFrame: Consent until 36 months after first dose
measure: Part C: Safety Evaluation of AZD0486
timeFrame: From signing of informed consent through completion of study treatment, an average of 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Duarte
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Palo Alto
country: United States
facility: Research Site
state: California
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: New York
country: United States
facility: Research Site
state: New York
city: Houston
country: United States
facility: Research Site
state: Texas
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Melbourne
country: Australia
facility: Research Site
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Caen
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Nantes
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Pierre Bénite
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Halle
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Münster
country: Germany
facility: Research Site
city: Wuerzburg
country: Germany
facility: Research Site
city: Bergamo
country: Italy
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Monza
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Kaohsiung City
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Surrey
country: United Kingdom
facility: Research Site
Study officials:
References: