AML (Acute Myeloid Leukemia)
Conditions
Keywords
Newly diagnosed AML, TP53-mutated AML
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.
Interventions
DRUGCLN-049
CLN-049 will be initiated using two step-up doses (SUDs), followed by the first target dose (TD) one week later, and weekly thereafter.
DRUGAzacitidine
Azacitidine 75 mg/m2 will initially be administered sub-cutaneous or intravenous on days 1 through 7 of a 28-day cycle
DRUGVenetoclax
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.
Sponsors
Cullinan Therapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients aged ≥ 18 years of age with newly diagnosed, previously untreated AML (including MDS/AML) 2. Patients are not candidates for intensive induction chemotherapy because they are either unfit or otherwise clinically unsuitable for anthracycline/ cytarabine-based induction therapy 3. White blood cell (WBC) count at the time of C1D1 ≤ 20,000/μL 4. 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. 5. Eastern Cooperative Oncology Group (ECOG) performance status is 0 to 2 6. The patient's laboratory values meet the following criteria: 1. Creatinine clearance (CrCl) ≥ 45 mL/min; 2. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) 3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN
Exclusion criteria
1. Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML to enter the study). 2. Diagnosis of acute promyelocytic leukemia or PML:RARA-positive AML. 3. Chronic myeloid leukemia in blast phase or AML with BCR:ABL1. 4. Mixed phenotype acute leukemia or acute leukemia of ambiguous lineage. 5. Active CNS involvement by AML. 6. Signs of leukostasis requiring urgent therapy. 7. Prior organ allograft, or prior allogeneic hematopoietic stem cell transplant within the last 12 months, or with active graph-versus-host disease. 8. Treatment with systemic glucocorticoid therapy or other immune-suppressive drugs ≤ 14 days prior to the first dose of CLN-049. 9. Patients with concomitant second malignancies requiring active treatment in the past 12 months, or if additional therapy is required or anticipated during study participation. 10. 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 11. Active uncontrolled infection until infection is treated and brought under control. 12. Has a history of, or a positive test for human immunodeficiency virus (HIV) 1/2 or primary immunodeficiency disease such as HIV. 13. Known history of hepatitis B, hepatitis C (HCV) infection, or acute hepatitis A. 14. Active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. 15. 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 16. History of the following events in conjunction with prior treatment with immunotherapy: Grade 3 or greater neurotoxicity, ocular toxicity, pneumonitis, myocarditis, or colitis; liver dysfunction meeting the laboratory criteria for Hy's Law. 17. Live virus vaccines within 28 days of the first dose of CLN-049, during treatment, and until the end of last dose of CLN-049. 18. QT interval corrected for heart rate using Fridericia's formula (QTcF) of ≥ 480 milliseconds. 19. Patient has a history of drug-related anaphylactic reactions to any components of CLN-049, or a history of Grade 4 anaphylactic reaction to any bispecific molecule or monoclonal antibody therapy. 20. Known history of prior human anti-human antibody response.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 48 weeks | 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) |
| Determine recommended dose/schedule of CLN-049 in combination with azacitidine and venetoclax | 48 weeks | — |
Countries
United States
Contacts
CONTACTTimna Serino
Outcome results
None listed