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

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

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 .

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory
• Intervention / Treatment: Drug: CB-012

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249-0001
      • The University of Alabama at Birmingham (UAB)
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • The Blood & Marrow Transplant Group of Georgia (BMTGA)
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center (MSKCC)
    • New York, New York, United States, 10022
      • Weill Cornell Medical College
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • TriStar Bone Marrow Transplant, LLC
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109-1023
      • Fred Hutchinson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation of CB-012; 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; CB-012 allogeneic CAR-T cell therapy targeting CLL-1 Cyclophosphamide and Fludarabine chemotherapy for lymphodepletion; Other Names: Cyclophosphamide; Fludarabine
Experimental: Dose Expansion of CB-012; 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; CB-012 allogeneic CAR-T cell therapy targeting CLL-1 Cyclophosphamide and Fludarabine chemotherapy for lymphodepletion; Other Names: Cyclophosphamide; Fludarabine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Caribou Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2024
• Primary Completion (Actual): May 30, 2025
• Study Completion (Actual): May 30, 2025

Study Registration Dates

• First Submitted: November 6, 2023
• First Submitted That Met QC Criteria: November 9, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 6, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: CB12A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No