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Recurrent Acute Myeloid LeukemiaPhase 1NCT05627232

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

A Phase 1 study testing Tazemetostat, Liposome-encapsulated Daunorubicin-Cytarabine and Bone Marrow Aspiration and Biopsy in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by Thomas Jefferson University at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tazemetostat, Liposome-encapsulated Daunorubicin-Cytarabine and Bone Marrow Aspiration and Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
28 Aug 2023to Jan 2029
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Gina Keiffer, MD contact

215-955-2929

gina.keiffer@jefferson.edu

United States1 site, 1 recruiting

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

    Gina Keiffer, MD, 215-955-2929, gina.keiffer@jefferson.edu

    Recruiting

Other trials in United States

About this study

Official title: A Two-Part Phase 1b Study Evaluating the Combination of Tazemetostat and CPX-351 (Part 1) and Palbociclib Pre-Treatment Followed by CPX-351 (Part 2) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

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.

Read the detailed description

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:

  1. 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:

  1. To determine whether treatment with the EZH2 inhibitor tazemetostat de-condenses the H3K27me3-marked chromatin of AML blasts.
  2. To determine whether cell cycle re-entry of AML cells after palbociclib treatment influences DNA damage and apoptosis induced by combining EZH2 inhibition with anthracycline-based therapy

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.

Being tested
Tazemetostat, Liposome-encapsulated Daunorubicin-Cytarabine, Bone Marrow Aspiration and Biopsy, Biospecimen Collection, Palbociclib
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TazemetostatDrug

    Also called 1403254-99-8, E7438, EPZ-6438, EPZ6438

    Given PO

  • Liposome-encapsulated Daunorubicin-CytarabineDrug

    Also called CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Daunorubicin and Cytarabine (Liposomal), Liposomal AraC-Daunorubicin CPX-351

    Given IV

  • Bone Marrow Aspiration and BiopsyProcedure or surgery

    Undergo bone marrow aspiration and biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • PalbociclibDrug

    Also called 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

    Given PO

Study groups in NCT05627232
Study groupRoleWhat they receive
Part I (tazemetostat, CPX-351)ExperimentalPatients 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.
Receives: 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)ExperimentalPatients 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.
Receives: Drug: Tazemetostat; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Biospecimen Collection; Drug: Palbociclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 1 year

Secondary outcomes (10)

  1. 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.

    Measured: Up to 1 year

  2. 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.

    Measured: Up to 1 year

  3. 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.

    Measured: Up to 1 year

  4. 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.

    Measured: Up to 1 year

  5. Induction failure/refractory acute myeloid leukemia (AML)

    Induction failure/refractory AML defined as failure to attain CR or CRi.

    Measured: Up to 1 year

  6. Time to blood count recovery

    95% confidence intervals will be calculated using Kaplan-Meier method.

    Measured: 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

  7. Relapse free survival

    95% confidence intervals will be calculated using Kaplan-Meier method.

    Measured: The time measured in months to relapse from day 1 of treatment, assessed up to 1 year

  8. Overall survival

    95% confidence intervals will be calculated using Kaplan-Meier method.

    Measured: The time measured in months from day 1 of treatment, assessed up to 1 year

  9. Rate of allogeneic stem cell transplantation

    Defined as the proportion of patients who undergo allogeneic stem cell transplantation during the study period.

    Measured: Up to 1 year

  10. Time to transplant

    95% confidence intervals will be calculated using Kaplan-Meier method.

    Measured: The time measured in months to allogeneic stem cell transplantation from day 1 of treatment, assessed up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Nov 2022
  2. Study start28 Aug 2023
  3. Primary completionJan 2028 (estimated)
  4. Study completionJan 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05627232
Sponsor's protocol ID
22G.769
Other IDs
JT 24252, 4100095617
Status last verified
Mar 2026
First submitted
16 Nov 2022
Last updated
12 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tazemetostat, Liposome-encapsulated Daunorubicin-Cytarabine and Bone Marrow Aspiration and Biopsy in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by Thomas Jefferson University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 12 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Gina Keiffer, MD (215-955-2929, gina.keiffer@jefferson.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of grade >= 3 non-hematologic dose limiting toxicities (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05627232.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2026.

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