CRISPR-Edited Allogeneic Anti-CLL-1 CAR-T Cell Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Study Overview
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Brief Summary
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CB-012 is an allogeneic chimeric antigen receptor (CAR-T) cell therapy that targets C-type lectin-like molecule-1 (CLL-1). This is a Phase 1 study to evaluate the safety, preliminary efficacy, and pharmacokinetics, of CB-012 (the study treatment) in adults with acute myeloid leukemia (AML) that has come back after prior treatment (relapsed) or did not respond or is no longer responding to other treatment (refractory). Participants must have received at least 1 but not more than 3 prior lines of treatment for AML .

Official Title
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A Phase 1, Multicenter, Open-Label Study of CB-012, a CRISPR-Edited Allogeneic Anti-CLL-1 CAR-T Cell Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia Refractory

Intervention / Treatment
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* Drug: CB-012


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of AML with either refractory or relapsed disease, Non-proliferative disease No more than 3 prior lines of therapy (induction, consolidation with or without allogeneic stem cell transplant, and maintenance are considered 1 line of therapy) No available therapy with reasonable survival benefit Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 and fit for allogeneic stem cell transplant Adequate renal, hepatic, pulmonary, and cardiac function, with specific laboratory criteria Women of child-bearing potential and men with a female partner who has child-bearing potential must agree to use acceptable, effective methods of birth control. Exclusion Criteria: Acute promyelocytic leukemia Extra-medullary disease (EMD) that is metabolically inactive by 18-FDG PET-CT Prior treatment with CAR-T cell therapy Allogeneic stem cell transplant within 100 days before lymphodepletion Active graft-vs-host disease requiring therapy Known active or prior history of central nervous system involvement Seropositive for or history of human immunodeficiency virus (HIV) Vaccinated with live, attenuated vaccine within 4 weeks prior to lymphodepletion Active hepatitis B or C infection Primary immunodeficiency or autoimmune disease Known life-threatening allergies, hypersensitivity, or intolerance to CB-012 or its excipients Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation of CB-012<br>Part A (Dose Escalation) of CB-012 with increasing doses using a 3+3 design, during which the MTD and/or RDE will be identified. | Drug: CB-012<br>* CB-012 allogeneic CAR-T cell therapy targeting CLL-1 Cyclophosphamide and Fludarabine chemotherapy for lymphodepletion<br>* Other names: Fludarabine;|
| Experimental: Dose Expansion of CB-012<br>Part B (Dose Expansion) - participants will be enrolled to receive CB-012 at the RDE and/or MTD determined in Part A in order to the determine the RP2D. | Drug: CB-012<br>* CB-012 allogeneic CAR-T cell therapy targeting CLL-1 Cyclophosphamide and Fludarabine chemotherapy for lymphodepletion<br>* Other names: Fludarabine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Part A) Number of patients with dose limiting toxicities (DLT) | Number of patients with DLTs during the 28 days following the first administration of CB-012. | 28 days | 
| (Part B) Overall Response Rate (ORR) | The ORR will be evaluated by European Leukemia Net (ELN) criteria | 12 months |