A Phase 1 interventional study of Tazemetostat and Liposome-encapsulated Daunorubicin-Cytarabine in Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, sponsored by Thomas Jefferson University. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-12.
Sponsored by Thomas Jefferson University · Phase 1, Interventional, and Treatment
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.
PRIMARY OBJECTIVE:
Part 1: To determine the RDFE of tazemetostat in combination with CPX-351 in patients with R/R-AML.
Part 2: To determine the RDFE of palbociclib pre-treatment prior to CPX-351 in patients with R/R-AML.
SECONDARY OBJECTIVE:
I. To evaluate the preliminary efficacy of tazemetostat in combination with CPX-351 (Part 1) and of palbociclib pre-treatment followed by CPX-351 (Part 2).
EXPLORATORY OBJECTIVES:
This is a phase 1b, single-institution, two-part, dose-escalation study utilizing tazemetostat in combination with CPX-351 (Part 1) and palbociclib pre-treatment followed by CPX-351 (Part 2) for patients with R/R-AML who are fit to receive intensive chemotherapy. The study will take place in two parts:
Part 1: Dose escalation via traditional 3+3 design of tazemetostat in combination with CPX-351 .
Part 2: Dose escalation via traditional 3+3 design of palbociclib pre-treatment followed by tazemetostat/CPX-351combination.
Once the RDFE of tazemetostat in combination with CPX-351 and the RDFE of palbociclib pre-treatment followed by CPX-351 have been determined, we hope to pursue further evaluation of the safety and preliminary efficacy of the three-drug combination pending further protocol amendment..
After completion of study treatment, patients are followed up at 3 months, 6 months, and 1 year for clinical outcomes including survival.
2,971 studies on the registry are indexed under Leukemia, Myeloid, Acute; 744 are open to participants now.
This study's planned enrollment of 24 is below the median of 41 across 2,508 interventional studies indexed under Leukemia, Myeloid, Acute.
Browse Leukemia, Myeloid, Acute studies →Thomas Jefferson University is the lead sponsor of 384 studies on the registry; 71 are open to participants now.
Of its 44 completed or terminated interventional studies of FDA-regulated products, 20 (45%) have results posted.
Counted across the registry records on this site, refreshed daily.
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
Exclusion Criteria:
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
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
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
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
Undergo bone marrow aspiration and biopsy
Undergo blood sample collection
Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection
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)-
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.
Time frame: Up to 1 year
Incidence of adverse events
Assessment of safety and tolerability: Incidence, nature, and severity of adverse events and incidence, nature and severity of treatment-emergent adverse events. 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 CTCAE 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.
Time frame: Up to 1 year
Complete response
Morphologic leukemia-free state: \< 5% blasts in bone marrow, no blasts with Auer rods or persistence of extramedullary disease. Morphologic complete response (CR): \< 5% blasts in bone marrow with transfusion independence, absolute neutrophil count (ANC) \> 1.0 x 10\^9/L, platelets \>= 100 x10\^9/L. CR without minimal residual disease: morphologic CR with negative molecular markers by real-time quantitative polymerase chain reaction or negative multi-parameter flow cytometry. CR with partial hematologic recovery (CRh): as \< 5% blasts in bone marrow with no evidence of disease and partial recovery of peripheral blood counts (ANC \> 0.5 x 10\^9/L and platelets \> 50 x 10\^9/L). CR with incomplete hematologic recovery (CRi): all CR criteria and transfusion independence but with persistence of neutropenia (ANC \< 1.0 x 10\^9/L) or thrombocytopenia (platelets \< 100 x 10\^9/L). Composite complete response: CR + CRh + CRi.
Time frame: Up to 1 year
Partial remission (PR)
PR is defined as decrease of at least 50% in the percentage of bone marrow blasts to 5% - 25% and normalization of blood counts.
Time frame: Up to 1 year
Relapse
Relapse is defined as reappearance of leukemic blasts in the peripheral blood or \> 5% blasts in the bone marrow not attributable to other cause (e.g., bone marrow regeneration after chemotherapy) or extramedullary relapse.
Time frame: Up to 1 year
Induction failure/refractory acute myeloid leukemia (AML)
Induction failure/refractory AML defined as failure to attain CR or CRi.
Time frame: Up to 1 year
Time to blood count recovery
95% confidence intervals will be calculated using Kaplan-Meier method.
Time frame: The number of days until ANC > 1.0 x 10^9/L and platelets >= 100 x 10^9/L from day 1 of treatment, assessed up to 1 year
Relapse free survival
95% confidence intervals will be calculated using Kaplan-Meier method.
Time frame: The time measured in months to relapse from day 1 of treatment, assessed up to 1 year
Overall survival
95% confidence intervals will be calculated using Kaplan-Meier method.
Time frame: The time measured in months from day 1 of treatment, assessed up to 1 year
Rate of allogeneic stem cell transplantation
Defined as the proportion of patients who undergo allogeneic stem cell transplantation during the study period.
Time frame: Up to 1 year
Time to transplant
95% confidence intervals will be calculated using Kaplan-Meier method.
Time frame: The time measured in months to allogeneic stem cell transplantation from day 1 of treatment, assessed up to 1 year
Deoxyribonucleic acid (DNA) damage and apoptosis
DNA damage (analysis of gammaH2AX-positive AML cells by confocal microscopy) and apoptosis (Annexin V and caspase 3 activation) will be assessed in S phase-enriched AML cells (16-24 hours post palbociclib treatment) following treatment with the EZH2 inhibitor tazemetostat to de-condense the H3K27me3-marked chromatin and chemotherapy (CPX-351) to induce DNA damage (double strand breaks).
Time frame: Up to day 5
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Thomas Jefferson University