A Phase 1b Study of CLN-049 in Combination With Azacitidine and Venetoclax in AML Patients

NCT07722767 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: CLN-049-AML-103
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 3

Brief Summary

A Phase 1b, open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of intravenously (IV) administered CLN-049 in combination with azacitidine (Aza) and venetoclax (Ven) in patients with newly diagnosed (ND) AML.

Conditions

AML (Acute Myeloid Leukemia)

Keywords

Newly diagnosed AML; TP53-mutated AML

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of adverse events (AEs)/adverse events of special interest (AESIs)/serious adverse events (SAEs) [safety and tolerability] of CLN-049 combined with azacitidine and venetoclax

  Safety assessments include: body measurements, vital signs, physical exam, EGOG (measure of patient function in terms of self-care, daily activity, and physical ability) performance status, lab assessments, ECGs, and ECHO/MUGA (tests to evaluate heart function)

  48 weeks

• Determine recommended dose/schedule of CLN-049 in combination with azacitidine and venetoclax

  48 weeks

Study Arms (2)

Part A: Dose Escalation

EXPERIMENTAL

Newly diagnosed AML patients treated with standard of care azacitidine and venetoclax in addition to CLN-049 in dose escalation cohorts

Drug: CLN-049; Drug: Azacitidine; Drug: Venetoclax

Part B: Dose Expansion

EXPERIMENTAL

Newly diagnosed AML patients treated with standard of care azacitidine and venetoclax in addition to CLN-049 at a dose determined in Part A (Dose Escalation)

Drug: CLN-049; Drug: Azacitidine; Drug: Venetoclax

Interventions

CLN-049 DRUG

CLN-049 will be initiated using two step-up doses (SUDs), followed by the first target dose (TD) one week later, and weekly thereafter.

Part A: Dose Escalation; Part B: Dose Expansion

Venetoclax DRUG

Venetoclax will initially be administered orally on days 1 through 28 of a 28-day cycle and then reduced to days 1 through 14 in consolidation cycles.

Part A: Dose Escalation; Part B: Dose Expansion

Azacitidine DRUG

Azacitidine 75 mg/m2 will initially be administered sub-cutaneous or intravenous on days 1 through 7 of a 28-day cycle

Part A: Dose Escalation; Part B: Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Patients aged ≥ 18 years of age with newly diagnosed, previously untreated AML (including MDS/AML)
• Patients are not candidates for intensive induction chemotherapy because they are either unfit or otherwise clinically unsuitable for anthracycline/ cytarabine-based induction therapy
• White blood cell (WBC) count at the time of C1D1 ≤ 20,000/μL
• Patients must have previously untreated AML; hydroxyurea for cytoreduction is permitted up to C1D1. Prior therapy for MDS is allowed except for hypomethylating agents and venetoclax.
• Eastern Cooperative Oncology Group (ECOG) performance status is 0 to 2
• The patient's laboratory values meet the following criteria:
• Creatinine clearance (CrCl) ≥ 45 mL/min;
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN

You may not qualify if:

• Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML to enter the study).
• Diagnosis of acute promyelocytic leukemia or PML:RARA-positive AML.
• Chronic myeloid leukemia in blast phase or AML with BCR:ABL1.
• Mixed phenotype acute leukemia or acute leukemia of ambiguous lineage.
• Active CNS involvement by AML.
• Signs of leukostasis requiring urgent therapy.
• Prior organ allograft, or prior allogeneic hematopoietic stem cell transplant within the last 12 months, or with active graph-versus-host disease.
• Treatment with systemic glucocorticoid therapy or other immune-suppressive drugs ≤ 14 days prior to the first dose of CLN-049.
• Patients with concomitant second malignancies requiring active treatment in the past 12 months, or if additional therapy is required or anticipated during study participation.
• Patients with any active autoimmune disease or a history of known or suspected autoimmune disease, or history of a syndrome that requires systemic corticosteroids or immunosuppressive medications
• Active uncontrolled infection until infection is treated and brought under control.
• Has a history of, or a positive test for human immunodeficiency virus (HIV) 1/2 or primary immunodeficiency disease such as HIV.
• Known history of hepatitis B, hepatitis C (HCV) infection, or acute hepatitis A.
• Active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
• Patients who have received an investigational agent (for any indication) within 5 half-lives of the agent and until toxicity from this has resolved to Grade 1 or less

Sponsors & Collaborators

• Cullinan Therapeutics Inc.: lead

Study Sites (3)

City of Hope

Duarte, California, 91010, United States

Location

New York University Langone Health

New York, New York, 10016, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Timna Serino

CONTACT

617-410-4650; ClinOps@cullinantx.com

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: July 15, 2026
• First Posted: July 23, 2026
• Study Start (Estimated): October 15, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): August 31, 2030
• Last Updated: July 23, 2026

Record last verified: 2026-07

Locations

US (3)