Tazemetostat and Palbociclib With CPX-351for R/R AML

NCT05627232 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 22G.769JT 242524100095617
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two-part phase Ib dose escalation study to evaluate the safety and preliminary efficacy of the combination of tazemetostat and CPX-351 (Part 1) and of pre-treatment with palbociclib followed by CPX-351 (Part 2) for patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). Part 1 of the study will seek to establish the safety, tolerability, biological activity and recommended dose for further evaluation (RDFE) of tazemetostat in combination with standard-dose CPX-351. Part 2 of the study will seek to establish the safety, tolerability, biological activity RDFE of pre-treatment palbociclib prior CPX-351.

Conditions

Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Incidence of grade >= 3 non-hematologic dose limiting toxicities

  The primary outcome measure will be grade \>= 3 non-hematologic dose limiting toxicities. Adverse events will be coded by organ system and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0. the calculation of adverse events incidences will be passed on number of patients per adverse event category. Standard proportions will be used to report rates of safety endpoints. Summary tables will be presented by dose level, seriousness, severity and relatedness.

  Up to 1 year

Secondary Outcomes (10)

• Incidence of adverse events

  Up to 1 year

• Complete response

  Up to 1 year

• Partial remission (PR)

  Up to 1 year

• Relapse

  Up to 1 year

• Induction failure/refractory acute myeloid leukemia (AML)

  Up to 1 year

Other Outcomes (1)

• Deoxyribonucleic acid (DNA) damage and apoptosis

  Up to day 5

Study Arms (2)

Part I (tazemetostat, CPX-351)

EXPERIMENTAL

Patients receive tazemetostat PO BID on days -1 to 6, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.

Drug: Tazemetostat; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Biospecimen Collection

Part II: (Palbociclib Pre-Treatment Followed by CPX-351)

EXPERIMENTAL

Patients receive palbociclib PO QD on days -3 to -1 and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.

Drug: Tazemetostat; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Biospecimen Collection; Drug: Palbociclib

Interventions

Tazemetostat DRUG

Given PO

Also known as: 1403254-99-8, E7438, EPZ-6438, EPZ6438, N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(oxan-4-yl)amino)-4-methyl-4'-((morpholin-4-yl)methyl)(1,1'-biphenyl)-3-carboxamide, N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-carboxamide

Part I (tazemetostat, CPX-351); Part II: (Palbociclib Pre-Treatment Followed by CPX-351)

Liposome-encapsulated Daunorubicin-Cytarabine DRUG

Given IV

Also known as: CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Daunorubicin and Cytarabine (Liposomal), Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, Vyxeos

Part I (tazemetostat, CPX-351); Part II: (Palbociclib Pre-Treatment Followed by CPX-351)

Bone Marrow Aspiration and Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Part I (tazemetostat, CPX-351); Part II: (Palbociclib Pre-Treatment Followed by CPX-351)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Part I (tazemetostat, CPX-351); Part II: (Palbociclib Pre-Treatment Followed by CPX-351)

Palbociclib DRUG

Given PO

Also known as: 571190-30-2, 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991, PD 991, PD-0332991, Pyrido(2,3-d)pyrimidin-7(8H)-one, 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(1-piperazinyl)-2-pyridinyl)amino)-

Part II: (Palbociclib Pre-Treatment Followed by CPX-351)

Eligibility Criteria

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

You may qualify if:

• Provide signed and dated informed consent form
• Willing to comply with all study procedures and be available for the duration of the study
• Male or female \>= 18 years of age
• Histologically confirmed acute myeloid leukemia (non-M3) relapsed from or refractory to at least 1 prior line of therapy. Bone marrow aspirate and biopsy within 28 days of screening is acceptable. If no prior bone marrow biopsy is available, bone marrow biopsy must be performed during screening unless:
• \* If the subject has \>= 20% myeloblasts present in the peripheral blood, a bone marrow biopsy is not necessary to meet this criterion
• Treatment with a prior investigational agent is acceptable so long as it has not been administered within 2 weeks of enrollment and any prior adverse effects have resolved to grade 1 or less with the exception of alopecia
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
• Life expectancy of at least 4 weeks
• Must be able to consume oral medication
• Subjects must have recovered from the toxic effect of any prior therapy to =\< grade 1 (except alopecia)
• Creatine clearance (CrCL) \>= 45
• Total bilirubin \< 2 x upper limit of normal (ULN)
• Female subjects of childbearing age must have a negative pregnancy test

You may not qualify if:

• Subjects with acute promyelocytic leukemia
• Subjects receiving any active chemotherapy agents (except hydroxyurea). Intrathecal methotrexate and cytarabine are permissible
• Subjects whose participation would result in a total cumulative dose of daunorubicin greater than 550 mg/m\^2 or greater than 450 mg/m\^2 if they previously received mediastinal radiation
• Subjects with evidence of active central nervous system (CNS) leukemia involvement. Lumbar puncture is not required for enrollment in the absence of neurologic symptoms
• Subjects must not be receiving growth factors (except erythropoietin)
• Subjects with currently active second malignancy with the exception of nonmelanoma skin cancer, carcinoma in situ of the cervix, resected prostate cancer with Gleason score =\< 6
• Subjects with unstable cardiac disease or uncontrolled arrhythmia
• Subjects with other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate to receive high-intensity therapy
• Subjects who are pregnant or breastfeeding
• Subjects with known allergic reactions to components of the study product(s)
• Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Pennsylvania Department of Health: collaborator

Study Sites (1)

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

tazemetostat; CPX-351; Injections; Daunorubicin; Cytarabine; Liposomes; Biopsy; Specimen Handling; palbociclib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Membranes, Artificial; Biomedical and Dental Materials; Drug Carriers; Dosage Forms; Pharmaceutical Preparations; Manufactured Materials; Technology, Industry, and Agriculture; Biomimetic Materials; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Gina Keiffer, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gina Keiffer, MD

CONTACT

215-955-2929; gina.keiffer@jefferson.edu

Study Design

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

Study Record Dates

• First Submitted: November 16, 2022
• First Posted: November 25, 2022
• Study Start: August 28, 2023
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: March 12, 2026

Record last verified: 2026-03

Locations

US (1)