AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia

NCT06137118 | Recruiting Phase 1 FDA Drug

• 1 other identifier: D7405C00001
• Study Type: interventional
• Target: 163
• Locations: 13 countries
• Sites: 80

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)

Conditions

B-cell Acute Lymphoblastic Leukemia (B-ALL)

Keywords

B-cell acute lymphoblastic leukemia; Leukemia; B-lymphocytes; AZD0486

Outcome Measures

Primary Outcomes (3)

• Part A: Frequency of DLTs

  DLTs are dose-limiting toxicities as defined in the study protocol

  Up to 28 days

• Parts A & B: Safety Evaluation of AZD0486

  Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in laboratory evaluations; QTc, and vital signs changes.

  From signing of informed consent through data cutoff, up to 42 months

• Parts B & C: Rate of CR within 3 cycles

  To evaluate the efficacy of AZD0486 based on NCCN response criteria (in Part B and C).

  Up to three cycles of 28 days each

Secondary Outcomes (16)

• Part A: Rate of CR within 3 cycles

  Up to 3 cycles of 28 days each

• Part A,B,C: Rate of CR/CRh and CR/CRh/CRi within 3 cycles

  Up to 3 cycles of 28 days each

• Parts A, B, C: Rate of CR, CR/CRh and CR/CRh/CRi at any time during the study

  From first dose to end of treatment or data cutoff, whichever comes first, assessed up to 42 months

• Parts A, B, C: Duration of CR, CR/CRh and CR/CRh/CRi

  From first dose to last progression or data cutoff, whichever comes first, assessed up to 42 months

• Parts A, B, C: Event-free survival (EFS)

  From First dose to last progression or data cutoff, whichever comes first, assessed up to 42 months

Study Arms (3)

Part A: AZD0486 Dose Escalation

EXPERIMENTAL

Ascending dose level cohorts of AZD0486 in B-ALL participants aged 12 years and above.

Drug: AZD0486

Part B: Dose Optimization

EXPERIMENTAL

Up to 2 cohorts will be evaluated prior declared safe-doses and schedules in order to determine the recommended phase 2 dose (RP2D). Participants, aged 12 years and above, will receive AZD0486 IV infusions and will be randomized in a 1:1 ratio.

Drug: AZD0486

Part C: Dose Expansion

EXPERIMENTAL

Part C will consist of 1 cohort of participants aged 12 years and above, treated with the optimal dose selected in Part B and receive IV AZD0486 monotherapy.

Drug: AZD0486

Interventions

AZD0486 DRUG

Investigational Product administered via intravenous infusion.

Part A: AZD0486 Dose Escalation; Part B: Dose Optimization; Part C: Dose Expansion

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 12 years and above (Parts A, B and C).
• Participants with B-cell Acute Lymphoblastic Leukemia with CD19 expression by local lab with:
• Bone marrow infiltration with \>/= 5% blasts
• Either relapsed or refractory after a minimum of 2 prior therapies or after 1 prior line of therapy if no SOC available option.
• Philadelphia positive participants are allowed in all parts of the study, 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%.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (80)

Research Site

Birmingham, Alabama, 35233, United States

WITHDRAWN

Research Site

Duarte, California, 91010, United States

RECRUITING

Research Site

Los Angeles, California, 90048, United States

RECRUITING

Research Site

Palo Alto, California, 94304, United States

RECRUITING

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Tampa, Florida, 33612, United States

RECRUITING

Research Site

Atlanta, Georgia, 30322, United States

RECRUITING

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Chicago, Illinois, 60637, United States

RECRUITING

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New York, New York, 10016, United States

RECRUITING

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Houston, Texas, 77030, United States

RECRUITING

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Richmond, Virginia, 23298, United States

RECRUITING

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Seattle, Washington, 98109, United States

WITHDRAWN

Research Site

Milwaukee, Wisconsin, 53226, United States

RECRUITING

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Melbourne, 3000, Australia

RECRUITING

Research Site

Porto Alegre, 90035903, Brazil

RECRUITING

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São Paulo, 01401-002, Brazil

RECRUITING

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São Paulo, 05652-900, Brazil

RECRUITING

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Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Research Site

Montreal, Quebec, H3T1C5, Canada

WITHDRAWN

Research Site

Montreal, Quebec, H4A 3J1, Canada

WITHDRAWN

Research Site

Changsha, 410008, China

RECRUITING

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Chengdu, 610041, China

RECRUITING

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Guangzhou, 510060, China

RECRUITING

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Guangzhou, 510280, China

RECRUITING

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Hangzhou, 310003, China

RECRUITING

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Nanjing, 210008, China

RECRUITING

Research Site

Nanjing, 210009, China

RECRUITING

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Suzhou, 215006, China

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Tianjin, 300020, China

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Zhengzhou, 450008, China

RECRUITING

Research Site

Caen, 14033, France

RECRUITING

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Marseille, 13009, France

RECRUITING

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Nantes, 44000, France

RECRUITING

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Paris, 75019, France

RECRUITING

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Pierre-Bénite, 69495, France

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Toulouse, 31059, France

RECRUITING

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Cologne, 50924, Germany

RECRUITING

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Düsseldorf, 40225, Germany

RECRUITING

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Essen, 45147, Germany

WITHDRAWN

Research Site

Frankfurt, 60590, Germany

RECRUITING

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Freiburg im Breisgau, 79106, Germany

RECRUITING

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Halle, 06120, Germany

RECRUITING

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Hamburg, 20246, Germany

RECRUITING

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Kiel, 24105, Germany

RECRUITING

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München, D-81337, Germany

RECRUITING

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Münster, 48149, Germany

RECRUITING

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Würzburg, 97080, Germany

RECRUITING

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Bergamo, 24127, Italy

RECRUITING

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Bologna, 40138, Italy

RECRUITING

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Monza, 20900, Italy

RECRUITING

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Naples, 80123, Italy

RECRUITING

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Roma, 00165, Italy

RECRUITING

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Bunkyō City, 113-8677, Japan

RECRUITING

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Chiba, 260-8677, Japan

RECRUITING

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Chūōku, 104-0045, Japan

RECRUITING

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Fukuoka, 810-8563, Japan

RECRUITING

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Kashiwa, 277-8577, Japan

RECRUITING

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Kyoto, 606-8507, Japan

RECRUITING

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Okayama, 701-1192, Japan

RECRUITING

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Osaka, 545-8586, Japan

RECRUITING

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Sapporo, 003-0006, Japan

RECRUITING

Research Site

Toyohashi, 441-8570, Japan

RECRUITING

Research Site

Yamagata, 990-9585, Japan

RECRUITING

Research Site

Seoul, 03080, South Korea

RECRUITING

Research Site

Seoul, 03722, South Korea

RECRUITING

Research Site

Seoul, 06351, South Korea

RECRUITING

Research Site

Seoul, 6591, South Korea

RECRUITING

Research Site

Barcelona, 08036, Spain

RECRUITING

Research Site

Barcelona, 8035, Spain

RECRUITING

Research Site

Madrid, 28025, Spain

RECRUITING

Research Site

Madrid, 28046, Spain

RECRUITING

Research Site

Salamanca, 37007, Spain

RECRUITING

Research Site

Valencia, 46026, Spain

ACTIVE NOT RECRUITING

Research Site

Kaohsiung City, 833401, Taiwan

RECRUITING

Research Site

Taichung, 40705, Taiwan

RECRUITING

Research Site

Tainan, 70403, Taiwan

RECRUITING

Research Site

Taipei, 10002, Taiwan

RECRUITING

Research Site

Taoyuan, 333, Taiwan

RECRUITING

Research Site

London, EC1A 7BE, United Kingdom

RECRUITING

Research Site

Manchester, M20 4BX, United Kingdom

RECRUITING

Research Site

Surrey, SM1 2DL, United Kingdom

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma; Leukemia

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 both Ph(+) and 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.

Study Record Dates

• First Submitted: November 3, 2023
• First Posted: November 18, 2023
• Study Start: December 29, 2023
• Primary Completion (Estimated): November 13, 2026
• Study Completion (Estimated): June 29, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

KR (4); CN (10); US (12); ES (6); CA (3); TW (5); GB (3); IT (5); AU (1); JP (11); DE (11); BR (3); FR (6)