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

NCT06128044 | Terminated Phase 1 FDA Drug

• 1 other identifier: CB12A
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 10

Brief Summary

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 .

Conditions

Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory

Outcome Measures

Primary Outcomes (2)

• (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

Study Arms (2)

Dose Escalation of CB-012

EXPERIMENTAL

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

Dose Expansion of CB-012

EXPERIMENTAL

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

Interventions

CB-012 DRUG

CB-012 allogeneic CAR-T cell therapy targeting CLL-1 Cyclophosphamide and Fludarabine chemotherapy for lymphodepletion

Also known as: Cyclophosphamide, Fludarabine

Dose Escalation of CB-012; Dose Expansion of CB-012

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Caribou Biosciences, Inc.: lead

Study Sites (10)

The University of Alabama at Birmingham (UAB)

Birmingham, Alabama, 35249-0001, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

The Blood & Marrow Transplant Group of Georgia (BMTGA)

Atlanta, Georgia, 30342, United States

Location

Weill Cornell Medical College

New York, New York, 10022, United States

Location

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, 10065, United States

Location

TriStar Bone Marrow Transplant, LLC

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109-1023, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

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

Study Record Dates

• First Submitted: November 6, 2023
• First Posted: November 13, 2023
• Study Start: February 8, 2024
• Primary Completion: May 30, 2025
• Study Completion: May 30, 2025
• Last Updated: June 11, 2025

Record last verified: 2025-05

Locations

US (10)