Trial Title:
A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination with Venetoclax/Azacitidine, Venetoclax, or 7+3 in Patients with AML
NCT ID:
NCT05735184
Condition:
Acute Myeloid Leukemia
Mixed Lineage Acute Leukemia
Mixed Lineage Leukemia Gene Mutation
Mixed Phenotype Acute Leukemia
Refractory AML
AML with Mutated NPM1
Acute Myeloid Leukemia Recurrent
Acute Myeloid Leukemia, in Relapse
NPM1 Mutation
KMT2Ar
Myeloid Sarcoma
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Sarcoma, Myeloid
Leukemia, Biphenotypic, Acute
Acute Disease
Cytarabine
Azacitidine
Venetoclax
Daunorubicin
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:
Ziftomenib
Description:
Oral Administration
Arm group label:
Dose Escalation: Ziftomenib/7+3 in 1L KMT2A-r (B-2)
Arm group label:
Dose Escalation: Ziftomenib/7+3 in 1L NPM1-m (A-2)
Arm group label:
Dose Escalation: Ziftomenib/Venetoclax/Azacitidine in R/R KMT2A-r (B-1)
Arm group label:
Dose Escalation: Ziftomenib/Venetoclax/Azacitidine in R/R NPM1-m (A-1)
Arm group label:
Dose Validation/Expansion: Ziftomenib/7+3 in 1L KMT2A-r (B-2)
Arm group label:
Dose Validation/Expansion: Ziftomenib/7+3 in 1L NPM1-m (A-2)
Arm group label:
Dose Validation/Expansion: Ziftomenib/Venetoclax in R/R NPM1-m (A-3)
Arm group label:
Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in 1L KMT2A-r (B-3)
Arm group label:
Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in 1L NPM1-m (A-4)
Arm group label:
Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in R/R KMT2A-r (B-1)
Arm group label:
Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in R/R NPM1-m (A-1)
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Oral Administration
Arm group label:
Dose Escalation: Ziftomenib/Venetoclax/Azacitidine in R/R KMT2A-r (B-1)
Arm group label:
Dose Escalation: Ziftomenib/Venetoclax/Azacitidine in R/R NPM1-m (A-1)
Arm group label:
Dose Validation/Expansion: Ziftomenib/Venetoclax in R/R NPM1-m (A-3)
Arm group label:
Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in 1L KMT2A-r (B-3)
Arm group label:
Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in 1L NPM1-m (A-4)
Arm group label:
Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in R/R KMT2A-r (B-1)
Arm group label:
Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in R/R NPM1-m (A-1)
Intervention type:
Drug
Intervention name:
Azacitidine
Description:
Subcutaneous or Intravenous Administration
Arm group label:
Dose Escalation: Ziftomenib/Venetoclax/Azacitidine in R/R KMT2A-r (B-1)
Arm group label:
Dose Escalation: Ziftomenib/Venetoclax/Azacitidine in R/R NPM1-m (A-1)
Arm group label:
Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in 1L KMT2A-r (B-3)
Arm group label:
Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in 1L NPM1-m (A-4)
Arm group label:
Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in R/R KMT2A-r (B-1)
Arm group label:
Dose Validation/Expansion: Ziftomenib/Venetoclax/Azacitidine in R/R NPM1-m (A-1)
Intervention type:
Drug
Intervention name:
Daunorubicin
Description:
Intravenous Administration
Arm group label:
Dose Escalation: Ziftomenib/7+3 in 1L KMT2A-r (B-2)
Arm group label:
Dose Escalation: Ziftomenib/7+3 in 1L NPM1-m (A-2)
Arm group label:
Dose Validation/Expansion: Ziftomenib/7+3 in 1L KMT2A-r (B-2)
Arm group label:
Dose Validation/Expansion: Ziftomenib/7+3 in 1L NPM1-m (A-2)
Intervention type:
Drug
Intervention name:
Cytarabine
Description:
Intravenous Administration
Arm group label:
Dose Escalation: Ziftomenib/7+3 in 1L KMT2A-r (B-2)
Arm group label:
Dose Escalation: Ziftomenib/7+3 in 1L NPM1-m (A-2)
Arm group label:
Dose Validation/Expansion: Ziftomenib/7+3 in 1L KMT2A-r (B-2)
Arm group label:
Dose Validation/Expansion: Ziftomenib/7+3 in 1L NPM1-m (A-2)
Summary:
This Phase 1 study will assess the safety, tolerability, and preliminary antileukemic
activity of ziftomenib in combination with venetoclax and azacitidine (ven/aza), ven, and
7+3 for two different molecularly-defined arms, NPM1-m and KMT2A-r.
Criteria for eligibility:
Criteria:
Key Inclusion Criteria:
- Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either
newly diagnosed or relapsed/refractory AML
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Adequate liver, renal, and cardiac function according to protocol defined criteria
- A female of childbearing potential must agree to use adequate contraception from the
time of screening through 180 days following the last dose of study intervention. A
male of childbearing potential must agree to use abstinence or adequate
contraception from the time of screening through 90 days following the last dose of
study intervention
Key Exclusion Criteria:
- Diagnosis of either acute promyelocytic leukemia or blast chronic myelomonocytic
leukemia
- Known history of BCR-ABL alteration
- Advanced malignant hepatic tumor [for patients receiving ven/aza combination]
- Administration of live attenuated vaccines within 14 days prior to, during, or after
treatment until B-cell recovery
- Active central nervous system (CNS) involvement by AML.
- Clinical signs/symptoms of leukostasis or WBC > 25,000 / microliter. Hydroxyurea
and/or leukapheresis are permitted to meet this criterion
- Not recovered to Grade ≤1 (NCI-CTCAE v5.0) from all nonhematological toxicities
except for alopecia
- Known clinically active human immunodeficiency virus, active hepatitis B or active
hepatitis C infection
- For newly diagnosed cohorts: received prior chemotherapy for leukemia, except
hydroxyurea and/or leukapheresis to control leukocytosis, prior treatment with
all-transretinoic acid for initially suspected acute promyelocytic leukemia, or
non-HMA therapy for prior myelodysplastic syndrome
- For relapsed/refractory cohorts: received chemotherapy, immunotherapy, radiotherapy,
or any ancillary therapy that is considered to be investigational < 14 days prior to
the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of
study drug
- Uncontrolled intercurrent illness including, but not limited to, cardiac illness as
defined in the protocol
- Mean corrected QT interval corrected for heart rate by Fredericia's formula (QTcF)
>480 ms on triplicate ECGs
- Uncontrolled infection
- Women who are pregnant or lactating
- An active malignancy and currently receiving chemotherapy for that malignancy or
disease that is uncontrolled/progressing
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Moores UC San Diego Cancer Center
Address:
City:
La Jolla
Zip:
92093
Country:
United States
Status:
Recruiting
Contact:
Last name:
Krisma Montalvo
Email:
k1montalvo@health.ucsd.edu
Facility:
Name:
USC University of Southern California / Norris Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christine Duran
Phone:
323-865-0371
Email:
duran_c@med.usc.edu
Facility:
Name:
UCLA - Bowyer Oncology Center
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Contact:
Last name:
Bruck Habtemariam
Phone:
310 794 0242
Email:
bhabtemariam@mednet.ucla.edu
Facility:
Name:
UCI Health Chao Family Comprehensive Cancer Center
Address:
City:
Orange
Zip:
92868
Country:
United States
Status:
Recruiting
Contact:
Last name:
Deepa Jeyakumar, MD
Phone:
877 827 8839
Email:
ucstudy@hs.uci.edu
Facility:
Name:
UC Health Blood Disorders and Cell Therapies Center - Anschutz Medical Campus
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christine McMahon, MD
Email:
CHRISTINE.MCMAHON@CUANSCHUTZ.EDU
Facility:
Name:
Colorado Blood Cancer Institute
Address:
City:
Denver
Zip:
80218
Country:
United States
Status:
Recruiting
Contact:
Last name:
Marcello Rotta, MD
Phone:
7207544800
Email:
PSLMDLCBCINewClinicPatient@HCAHealthcare.com
Facility:
Name:
Yale Cancer Center and Smilow Cancer Hospital
Address:
City:
New Haven
Zip:
06510
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christina Wiess
Phone:
2037373472
Email:
christina.wiess@yale.edu
Facility:
Name:
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Status:
Recruiting
Contact:
Phone:
3126951102
Email:
cancertrials@northwestern.edu
Facility:
Name:
The University of Kansas Cancer Center
Address:
City:
Fairway
Zip:
66205
Country:
United States
Status:
Recruiting
Contact:
Last name:
Thania Medrano
Email:
tmedrano@kumc.edu
Facility:
Name:
Norton Cancer Institute - St. Matthews
Address:
City:
Louisville
Zip:
40207
Country:
United States
Status:
Recruiting
Contact:
Phone:
(502)899-3366
Email:
leukemia-NCIResearch@nortonhealthcare.org
Facility:
Name:
Ochsner MD Anderson Cancer Center
Address:
City:
Jefferson
Zip:
70121
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amanda Woolery, RN
Phone:
504 842 0275
Email:
amanda.woolery@ochsner.org
Facility:
Name:
Massachusetts General Hospital
Address:
City:
Boston
Zip:
02114
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amir Fathi, MD
Phone:
6177241124
Facility:
Name:
Karmanos Cancer Institute
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Karmanos Cancer Institute
Phone:
8005276266
Facility:
Name:
University of Minnesota
Address:
City:
Minneapolis
Zip:
55455
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mark Juckett, MD
Email:
Juck0001@umn.edu
Facility:
Name:
Rutgers Cancer Institute
Address:
City:
New Brunswick
Zip:
08903
Country:
United States
Status:
Recruiting
Contact:
Last name:
Anita Trupiano
Email:
ar2069@cinj.rutgers.edu
Facility:
Name:
Roswell Park Comprehensive Cancer Center
Address:
City:
Buffalo
Zip:
14203
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amaris Pilcher
Phone:
716-845-5602
Email:
leukresearchteam@roswellpark.org
Facility:
Name:
New York - Presbyterian / Weill Cornell Medicine
Address:
City:
New York
Zip:
10021
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tania J Curcio
Email:
tjc9003@med.cornell.edu
Facility:
Name:
Mount Sinai - Ruttenberg Treatment Center
Address:
City:
New York
Zip:
10029
Country:
United States
Status:
Recruiting
Contact:
Last name:
Marina Kremyanskaya, MD, PhD
Email:
Marina.Kremyanskaya@mssm.edu
Facility:
Name:
Stony Brook Cancer Center
Address:
City:
Stony Brook
Zip:
11794
Country:
United States
Status:
Recruiting
Contact:
Last name:
Zita Makselyte
Email:
zita.makselyte@stonybrookmedicine.edu
Facility:
Name:
Duke Blood Cancer Center
Address:
City:
Durham
Zip:
27705
Country:
United States
Status:
Recruiting
Contact:
Last name:
Quinna Lawson
Email:
quinna.marshburn@duke.edu
Facility:
Name:
Cleveland Clinic
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Status:
Recruiting
Contact:
Last name:
Anjali Advani, MD
Email:
ADVANIA@ccf.org
Facility:
Name:
OU Health Stephenson Cancer Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Cynthia Lowery
Email:
Cynthia-Lowery@ouhsc.edu
Facility:
Name:
Hospital of the University of Pennsylvania
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jessica Ritter
Email:
Jessica.Ritter@pennmedicine.upenn.edu
Facility:
Name:
TriStar Bone Marrow Transplant
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ask Sarah
Phone:
8444824812
Facility:
Name:
Sarah Cannon Research Institute - St. David's South Austin Medical Center / Texas Oncology South Austin
Address:
City:
Austin
Zip:
78704
Country:
United States
Status:
Recruiting
Facility:
Name:
UT Southwestern - Simmons Cancer Center
Address:
City:
Dallas
Zip:
75235
Country:
United States
Status:
Recruiting
Contact:
Last name:
Yazan Madanat, MD
Phone:
833-722-6237
Email:
canceranswerline@utsouthwestern.edu
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ramya Ganesh
Phone:
7137925640
Email:
rganesh@mdanderson.org
Contact backup:
Last name:
Ghayas Issa, MD
Facility:
Name:
UW Health - Carbone Cancer Center
Address:
City:
Madison
Zip:
53792
Country:
United States
Status:
Recruiting
Contact:
Last name:
UW Cancer Connect
Phone:
800 622 8922
Email:
clinicaltrials@cancer.wisc.edu
Start date:
July 18, 2023
Completion date:
May 2027
Lead sponsor:
Agency:
Kura Oncology, Inc.
Agency class:
Industry
Source:
Kura Oncology, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05735184
