Trial Title:
Palbociclib or Tazemetostat in Combination With CPX-351 for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
NCT ID:
NCT05627232
Condition:
Recurrent Acute Myeloid Leukemia
Refractory Acute Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Diphenhydramine
Promethazine
Cytarabine
Daunorubicin
Palbociclib
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tazemetostat
Description:
Given PO
Arm group label:
Part I (tazemetostat, CPX-351)
Other name:
1403254-99-8
Other name:
E7438
Other name:
EPZ-6438
Other name:
EPZ6438
Other name:
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
Other name:
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
Intervention type:
Drug
Intervention name:
Liposome-encapsulated Daunorubicin-Cytarabine
Description:
Given IV
Arm group label:
Part I (tazemetostat, CPX-351)
Arm group label:
Part II (palbociclib, CPX-351)
Other name:
CPX-351
Other name:
Cytarabine-Daunorubicin Liposome for Injection
Other name:
Daunorubicin and Cytarabine (Liposomal)
Other name:
Liposomal AraC-Daunorubicin CPX-351
Other name:
Liposomal Cytarabine-Daunorubicin
Other name:
Liposome-encapsulated Combination of Daunorubicin and Cytarabine
Other name:
Vyxeos
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration and Biopsy
Description:
Undergo bone marrow aspiration and biopsy
Arm group label:
Part I (tazemetostat, CPX-351)
Arm group label:
Part II (palbociclib, CPX-351)
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Part I (tazemetostat, CPX-351)
Arm group label:
Part II (palbociclib, CPX-351)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Palbociclib
Description:
Given PO
Arm group label:
Part II (palbociclib, CPX-351)
Other name:
571190-30-2
Other name:
6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one
Other name:
Ibrance
Other name:
PD 0332991
Other name:
PD 332991
Other name:
PD 991
Other name:
PD-0332991
Other name:
Pyrido(2,3-d)pyrimidin-7(8H)-one
Other name:
6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(1-piperazinyl)-2-pyridinyl)amino)-
Summary:
This phase I trial tests the safety, side effects, and best dose of palbociclib or
tazemetostat in combination with CPX-351 in treating patients with acute myeloid leukemia
(AML) that has come back (relapsed) or does not respond to treatment (refractory).
CPX-351 is a combination of the chemotherapy drugs, daunorubicin and cytarabine, which is
the standard of care for AML. Chemotherapy drugs work in different ways to stop the
growth of cancer cells, either by killing the cells, by stopping them from dividing, or
by stopping them from spreading. Palbociclib and tazemetostat are enzyme inhibitor drugs
that are approved for treating certain cancers but not AML. These drugs may stop the
growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving
CPX-351 chemotherapy with enzyme inhibitors palbociclib or tazemetostat may kill more
cancer cells.
Detailed description:
PRIMARY OBJECTIVE:
Part 1: To determine the maximum tolerated dose (MTD) of tazemetostat in combination with
CPX-351 in patients with relapsed/refractory (R/R)-acute myeloid leukemia (AML).
Part 2: To determine the maximum tolerated dose (MTD) of palbociclib in combination with
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 CPX-351 following pre-treatment with palbociclib (part 2).
EXPLORATORY OBJECTIVES:
I. To determine whether treatment with the EZH2 inhibitor tazemetostat de-condenses the
H3K27me3-marked chromatin of AML blasts.
Il. 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.
OUTLINE: This is a dose-escalation study of tazemetostat or palbociclib in combination
with fixed dose CPX-351. Patients are assigned to 1 of 2 parts.
PART I: Patients receive tazemetostat orally (PO) twice a day (BID) on days -1 to 6, and
CPX-351 intravenously (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.
PART II: Patients receive palbociclib PO daily (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.
After completion of study treatment, patients are followed up at 3 months, 6 months, and
1 year for clinical outcomes including survival.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Thomas Jefferson University Hospital
Address:
City:
Philadelphia
Zip:
19107
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gina Keiffer, MD
Phone:
215-955-2929
Email:
gina.keiffer@jefferson.edu
Start date:
August 28, 2023
Completion date:
January 2026
Lead sponsor:
Agency:
Thomas Jefferson University
Agency class:
Other
Source:
Thomas Jefferson University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05627232
