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RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

Study of AZD4512 Monotherapy or in Combination With Anticancer Agents in Participants With Acute Lymphoblastic Leukemia

A Modular Phase I/II, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Preliminary Efficacy of AZD4512 Monotherapy or in Combination With Anticancer Agent(s) in Participants With Acute Lymphoblastic Leukemia

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

The study is intended to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of AZD4512 in patients with relapsed/refractory B-Cell acute lymphoblastic leukemia (r/r B-ALL).

Who May Be Eligible (Plain English)

Who May Qualify: - 1\. Age: - 16 years old in Module 1 (US only: ≥18year) - 12 years old in Module 2 2\. Diagnosis: Known Diagnosis of CD22-positive B-ALL based on criteria established by WHO (Alaggio et al. 2022). - Participants must have relapsed or refractory B-ALL ('relapsed' defined as bone marrow blasts \> 5% or reappearance of blasts in PB) - Module 1 (DE): Ph(-) B-ALL and Ph(+) B-ALL - R/R - Backfill of Module 1 and Module 2 (DO): R/R Ph(-) B-ALL 3\. Performance status (ECOG ≤ 2; KPS ≥ 50; LPS ≥ 50) 4\. Peripheral lymphoblast count \< 10,000/µL (may receive cytoreduction prior to C1D1 per protocol-specified criteria) 5\. At least 2 prior therapies with refractoriness or relapse, or 1 prior therapy with refractoriness or relapse and no standard options available. Participants who have received prior CD22 targeted therapies are eligible. - Ph+ B-ALL (Module 1 DE only): intolerant to or have contraindications to TKI therapy or R/R disease despite treatment with at least 2 prior TKIs or at least one 3rd generation TKI 6\. Prior DLI \>4 weeks, prior cell therapy or autoHSCT \>8 weeks, alloHSCT \>12 weeks Who Should NOT Join This Trial: 1. Burkitt lymphoma and leukemia 2. Isolated extramedullary disease; Active testicular or CNS (\> CNS1) involvement 3. Unresolved non-heme toxicities Grade ≥ 2 (except alopecia, stable Grade ≤ 2 neuropathy, vitiligo, endocrine disorders controlled with therapy) 4. History of drug-induced non-infectious ILD/pneumonitis requiring oral or IV steroids or supplemental oxygen or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening 5. Prior/concomitant therapy - Cytotoxic treatment within 14 days (except ALL maintenance medications or cytoreduction) - Biologic (immuno-oncology) treatment within 28 days or 5 half-lives (whichever is shorter) - Non-CNS radiation within 2 weeks \& CNS radiation within 4 weeks ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * 1\. Age: * 16 years old in Module 1 (US only: ≥18year) * 12 years old in Module 2 2\. Diagnosis: Known Diagnosis of CD22-positive B-ALL based on criteria established by WHO (Alaggio et al. 2022). * Participants must have relapsed or refractory B-ALL ('relapsed' defined as bone marrow blasts \> 5% or reappearance of blasts in PB) * Module 1 (DE): Ph(-) B-ALL and Ph(+) B-ALL - R/R * Backfill of Module 1 and Module 2 (DO): R/R Ph(-) B-ALL 3\. Performance status (ECOG ≤ 2; KPS ≥ 50; LPS ≥ 50) 4\. Peripheral lymphoblast count \< 10,000/µL (may receive cytoreduction prior to C1D1 per protocol-specified criteria) 5\. At least 2 prior therapies with refractoriness or relapse, or 1 prior therapy with refractoriness or relapse and no standard options available. Participants who have received prior CD22 targeted therapies are eligible. * Ph+ B-ALL (Module 1 DE only): intolerant to or have contraindications to TKI therapy or R/R disease despite treatment with at least 2 prior TKIs or at least one 3rd generation TKI 6\. Prior DLI \>4 weeks, prior cell therapy or autoHSCT \>8 weeks, alloHSCT \>12 weeks Exclusion Criteria: 1. Burkitt lymphoma and leukemia 2. Isolated extramedullary disease; Active testicular or CNS (\> CNS1) involvement 3. Unresolved non-heme toxicities Grade ≥ 2 (except alopecia, stable Grade ≤ 2 neuropathy, vitiligo, endocrine disorders controlled with therapy) 4. History of drug-induced non-infectious ILD/pneumonitis requiring oral or IV steroids or supplemental oxygen or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening 5. Prior/concomitant therapy * Cytotoxic treatment within 14 days (except ALL maintenance medications or cytoreduction) * Biologic (immuno-oncology) treatment within 28 days or 5 half-lives (whichever is shorter) * Non-CNS radiation within 2 weeks \& CNS radiation within 4 weeks * Medications known to prolong QTc and/or associated with Torsades de Pointes within 5 half-lives * Strong inhibitors of CYP 3A4 within 14 days or 5 half-lives (whichever is longer) * Investigational agents or study interventions in the last 30 days or 5 half-lives prior to the first dose of AZD4512 whichever is longer. If the investigational product is an agent to treat B-ALL and meets the modality criteria, then a specific washout period must be adhered to instead.

Treatments Being Tested

COMBINATION_PRODUCT

AZD4512 monotherapy

Patients will receive AZD4512 as monotherapy via intravenous infusion. AZD4512 is an antibody-drug conjugate targeting CD22

Locations (20)

Research Site
Duarte, California, United States
Research Site
Jacksonville, Florida, United States
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Chicago, Illinois, United States
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Iowa City, Iowa, United States
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Franklin, Tennessee, United States
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Houston, Texas, United States
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Melbourne, Australia
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Vancouver, British Columbia, Canada
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Toronto, Ontario, Canada
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Guangzhou, China
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Tianjin, China
Research Site
Bunkyō City, Japan
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Chūōku, Japan
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Seoul, South Korea
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Seoul, South Korea
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Seoul, South Korea
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Seoul, South Korea
Research Site
Badalona(Barcelona), Spain
Research Site
Barcelona, Spain
Research Site
Salamanca, Spain