Trial Title:
Venetoclax in Combination With ASTX727 for the Treatment of Chronic Myelomonocytic Leukemia and Other Myelodysplastic Syndrome/Myeloproliferative Neoplasm
NCT ID:
NCT05600894
Condition:
Chronic Myelomonocytic Leukemia
Myelodysplastic Syndrome
Myelodysplastic Syndrome With Excess Blasts
Myeloproliferative Neoplasm
Conditions: Official terms:
Leukemia
Neoplasms
Preleukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Myeloproliferative Disorders
Anemia, Refractory, with Excess of Blasts
Syndrome
Venetoclax
Decitabine
Decitabine and cedazuridine drug combination
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Crossover Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood and buccal samples
Arm group label:
Arm I (ASTX727, venetoclax)
Arm group label:
Arm II (ASTX727)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow biopsy
Arm group label:
Arm I (ASTX727, venetoclax)
Arm group label:
Arm II (ASTX727)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Drug
Intervention name:
Decitabine and Cedazuridine
Description:
Given PO
Arm group label:
Arm I (ASTX727, venetoclax)
Arm group label:
Arm II (ASTX727)
Other name:
ASTX 727
Other name:
ASTX-727
Other name:
ASTX727
Other name:
C-DEC
Other name:
CDA Inhibitor E7727/Decitabine Combination Agent ASTX727
Other name:
Cedazuridine/Decitabine Combination Agent ASTX727
Other name:
Cedazuridine/Decitabine Tablet
Other name:
DEC-C
Other name:
Inaqovi
Other name:
Inqovi
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Given PO
Arm group label:
Arm I (ASTX727, venetoclax)
Arm group label:
Arm II (ASTX727)
Other name:
ABT 199
Other name:
ABT-0199
Other name:
ABT-199
Other name:
ABT199
Other name:
GDC 0199
Other name:
GDC-0199
Other name:
GDC0199
Other name:
RG7601
Other name:
Venclexta
Other name:
Venclyxto
Summary:
This phase II trial tests whether decitabine and cedazuridine (ASTX727) in combination
with venetoclax work better than ASTX727 alone at decreasing symptoms of bone marrow
cancer in patients with chronic myelomonocytic leukemia (CMML), myelodysplastic
syndrome/myeloproliferative neoplasm (MDS/MPN) with excess blasts. Blasts are immature
blood cells. Decitabine is in a class of medications called hypomethylation agents. It
works by helping the bone marrow produce normal blood cells and by killing abnormal cells
in the bone marrow. Cobimetinib is used in patients whose cancer has a mutated (changed)
form of a gene called BRAF. It is in a class of medications called kinase inhibitors. It
works by blocking the action of an abnormal protein that signals cancer cells to
multiply. This helps slow or stop the spread of cancer cells. Venetoclax is in a class of
medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer
cells by blocking Bcl-2, a protein needed for cancer cell survival. The combination of
ASTX727 and venetoclax may be more effective in reducing the cancer signs and symptoms in
patients with CMML, or MDS/MPN with excess blasts.
Detailed description:
PRIMARY OBJECTIVE:
I. To evaluate the complete remission rates of ASTX727 and ASTX727 plus venetoclax in
subjects with chronic myelomonocytic leukemia (CMML) and non-CMML myelodysplastic
syndrome (MDS)/myeloproliferative neoplasm (MPN) with excess (>= 5%) blasts.
SECONDARY OBJECTIVES:
I. To evaluate the overall response rate (complete response [CR] + partial response [PR]
+ marrow response with erythroid response) of ASTX727 versus ASTX727 + venetoclax in this
patient population.
II. To determine the overall survival, progression-free survival, allogeneic
hematopoietic stem cell transplantation rate, clearance of the malignant clone, clonality
at time of hematologic remission, number of red cell and platelet transfusions required
and toxicity of ASTX727 versus ASTX727 + venetoclax.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I (COMBINATION THERAPY): Patients receive ASTX727 orally (PO) daily (QD) for 5
consecutive days starting on day 3 of treatment cycle 1; followed by day 1 of each
subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or
unacceptable toxicity. Patients also receive venetoclax PO QD on days 1 through 14 of
each treatment cycle. Cycles repeat every 28 days in the absence of disease progression
or unacceptable toxicity. Patients also undergo bone marrow biopsies, and collection of
blood and buccal samples throughout the study.
ARM II (MONO THERAPY): Patients receive ASTX727 PO QD for 5 consecutive days starting on
day 3 of treatment cycle 1; followed by day 1 of each subsequent cycle. Cycles repeat
every 28 days in the absence of disease progression or unacceptable toxicity. Patients
who do not have response to treatment may cross over to Arm I. Patients also undergo bone
marrow biopsies, and collection of blood and buccal samples throughout the study.
After completion of study treatment, patients are followed up every 6 months for 5 years
or until death, whichever occurs first.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- A diagnosis of an MDS/MPN "overlap" syndrome with >= 5% marrow blasts. Hydroxyurea
may be used to control counts up until the start of therapy
- White blood cell (WBC) < 10,000/mm^3. Treatment with hydroxyurea is permitted to
lower the WBC to reach this criterion. The WBC should be determined >= 24 hours
after the last dose of hydroxyurea
- Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of ASTX727 in combination with venetoclax in patients < 18 years of age,
children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless considered due to
Gilbert's syndrome)
- Aspartate aminotransferase (AST) serum aspartate aminotransferase (SGOT)/alanine
aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) =< 3.0 x
institutional ULN OR =< 5.0 x institutional ULN for patients with liver metastases
- Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial. Hormonal therapy for prior
or concurrent malignancy is allowed
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
- Ability to understand and the willingness to sign a written informed consent
document. Participants with impaired decision-making capacity (IDMC) who have a
legally authorized representative (LAR) and/or family member available will also be
eligible
- Ability to swallow pills
Exclusion Criteria:
- Patients with need for emergent disease-directed therapy excluding hydroxyurea
- More than one cycle of previous MDS/MPN-directed therapy, or MDS-directed therapy
including lenalidomide and hypomethylating agent (HMAs) such as decitabine or
azacitidine, excluding hydroxyurea. Prior use of erythropoietin stimulating agents
(ESA) and thrombopoietic agents is allowed, but must be discontinued 4 weeks prior
to study treatment
- Patients currently or previously receiving an investigational agent or device within
4 weeks of the first dose of treatment
- Patients with symptomatic uncontrolled central nervous system (CNS) disease. Imaging
to confirm the absence of brain metastases is not required. Patients with spinal
cord compression unless considered to have received definitive treatment for this
and evidence of clinically stable disease for 28 days
- Patients who have consumed grapefruit, grapefruit products, Seville oranges
(including marmalade containing Seville oranges) or starfruit within 3 days prior to
the initiation of study treatment and are unwilling to discontinue consumption of
these throughout the receipt of study drug
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to ASTX727 or venetoclax
- Patients with uncontrolled intercurrent illness (e.g. requiring intravenous therapy)
at the discretion of the investigator
- Pregnant women are excluded from this study because venetoclax and ASTX727 have the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with venetoclax, breastfeeding should be discontinued if the mother is
treated with venetoclax. These potential risks may also apply to other agents used
in this study. Patients must be post-menopausal or with evidence of non-childbearing
status for women of childbearing potential: negative urine or serum pregnancy test
within 28 days of study treatment and confirmed prior to treatment on Day 1.
- Post-menopausal is defined as:
- Amenorrheic for 1 year or more following cessation of exogenous hormonal
treatments
- Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in
the post-menopausal range for women under 50 years of age
- Radiation-induced oophorectomy with last menses > 1 year ago
- Chemotherapy-induced menopause with > 1 year interval since last menses
- Surgical sterilization (bilateral oophorectomy or hysterectomy)
- Women of child-bearing potential must agree to use adequate contraception
(hormonal birth control or abstinence) prior to study entry and for the
duration of study participation, and for 6 months following completion of study
treatment. Should a woman become pregnant or suspect she is pregnant while she
or her partner is participating in this study, she should inform her treating
physician immediately. Men treated or enrolled on this protocol must also agree
to use adequate contraception (latex or synthetic condom or abstinence) prior
to the study, for the duration of study participation, and 3 months after
completion of venetoclax and ASTX727 administration
- Patients with any other medical condition for which the expected survival is below
12 months
- Patients with a prior or concurrent malignancy whose natural history or treatment
has the potential to interfere with the safety or assessment of the investigational
regimen
- Patients with active infection at the time of study entry
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UC Irvine Health Cancer Center-Newport
Address:
City:
Costa Mesa
Zip:
92627
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-827-8839
Investigator:
Last name:
Deepa Jeyakumar
Email:
Principal Investigator
Facility:
Name:
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Address:
City:
Irvine
Zip:
92612
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-827-8839
Email:
ucstudy@uci.edu
Investigator:
Last name:
Deepa Jeyakumar
Email:
Principal Investigator
Facility:
Name:
UCI Health Laguna Hills
Address:
City:
Laguna Hills
Zip:
92653
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-827-8839
Email:
ucstudy@uci.edu
Investigator:
Last name:
Deepa Jeyakumar
Email:
Principal Investigator
Facility:
Name:
Los Angeles General Medical Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
323-865-0451
Email:
uscnorrisinfo@med.usc.edu
Investigator:
Last name:
Abdullah Ladha
Email:
Principal Investigator
Facility:
Name:
USC / Norris Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
323-865-0451
Investigator:
Last name:
Abdullah Ladha
Email:
Principal Investigator
Facility:
Name:
UC Irvine Health/Chao Family Comprehensive Cancer Center
Address:
City:
Orange
Zip:
92868
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-827-8839
Email:
ucstudy@uci.edu
Investigator:
Last name:
Deepa Jeyakumar
Email:
Principal Investigator
Facility:
Name:
University of California Davis Comprehensive Cancer Center
Address:
City:
Sacramento
Zip:
95817
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
916-734-3089
Investigator:
Last name:
Brian A. Jonas
Email:
Principal Investigator
Facility:
Name:
Yale University
Address:
City:
New Haven
Zip:
06520
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
203-785-5702
Email:
canceranswers@yale.edu
Investigator:
Last name:
Rory M. Shallis
Email:
Principal Investigator
Facility:
Name:
Mayo Clinic in Florida
Address:
City:
Jacksonville
Zip:
32224-9980
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
855-776-0015
Investigator:
Last name:
Talha Badar
Email:
Principal Investigator
Facility:
Name:
Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
312-695-1301
Email:
cancer@northwestern.edu
Investigator:
Last name:
Jamile Shammo
Email:
Principal Investigator
Facility:
Name:
University of Chicago Comprehensive Cancer Center
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
773-702-8222
Email:
cancerclinicaltrials@bsd.uchicago.edu
Investigator:
Last name:
Olatoyosi M. Odenike
Email:
Principal Investigator
Facility:
Name:
UC Comprehensive Cancer Center at Silver Cross
Address:
City:
New Lenox
Zip:
60451
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
773-702-8222
Email:
cancerclinicaltrials@bsd.uchicago.edu
Investigator:
Last name:
Olatoyosi M. Odenike
Email:
Principal Investigator
Facility:
Name:
University of Chicago Medicine-Orland Park
Address:
City:
Orland Park
Zip:
60462
Country:
United States
Status:
Suspended
Facility:
Name:
University of Kansas Cancer Center
Address:
City:
Kansas City
Zip:
66160
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
913-588-3671
Email:
KUCC_Navigation@kumc.edu
Investigator:
Last name:
Abdulraheem M. Yacoub
Email:
Principal Investigator
Facility:
Name:
University of Kansas Hospital-Westwood Cancer Center
Address:
City:
Westwood
Zip:
66205
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
913-588-3671
Email:
KUCC_Navigation@kumc.edu
Investigator:
Last name:
Abdulraheem M. Yacoub
Email:
Principal Investigator
Facility:
Name:
University of Maryland/Greenebaum Cancer Center
Address:
City:
Baltimore
Zip:
21201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-888-8823
Investigator:
Last name:
Sandrine Niyongere
Email:
Principal Investigator
Facility:
Name:
Beth Israel Deaconess Medical Center
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
617-667-9925
Investigator:
Last name:
Malgorzata McMasters
Email:
Principal Investigator
Facility:
Name:
Montefiore Medical Center-Einstein Campus
Address:
City:
Bronx
Zip:
10461
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
718-379-6866
Email:
eskwak@montefiore.org
Investigator:
Last name:
Ioannis Mantzaris
Email:
Principal Investigator
Facility:
Name:
Montefiore Medical Center-Weiler Hospital
Address:
City:
Bronx
Zip:
10461
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
718-379-6866
Email:
eskwak@montefiore.org
Investigator:
Last name:
Ioannis Mantzaris
Email:
Principal Investigator
Facility:
Name:
Montefiore Medical Center - Moses Campus
Address:
City:
Bronx
Zip:
10467
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
718-379-6866
Email:
eskwak@montefiore.org
Investigator:
Last name:
Ioannis Mantzaris
Email:
Principal Investigator
Facility:
Name:
UNC Lineberger Comprehensive Cancer Center
Address:
City:
Chapel Hill
Zip:
27599
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
877-668-0683
Email:
cancerclinicaltrials@med.unc.edu
Investigator:
Last name:
Joshua F. Zeidner
Email:
Principal Investigator
Facility:
Name:
Wake Forest University Health Sciences
Address:
City:
Winston-Salem
Zip:
27157
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
336-713-6771
Investigator:
Last name:
Rupali R. Bhave
Email:
Principal Investigator
Facility:
Name:
University of Cincinnati Cancer Center-UC Medical Center
Address:
City:
Cincinnati
Zip:
45219
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
513-584-7698
Email:
cancer@uchealth.com
Investigator:
Last name:
Emily K. Curran
Email:
Principal Investigator
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-293-5066
Email:
Jamesline@osumc.edu
Investigator:
Last name:
Kristin Koenig
Email:
Principal Investigator
Facility:
Name:
University of Cincinnati Cancer Center-West Chester
Address:
City:
West Chester
Zip:
45069
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
513-584-7698
Email:
cancer@uchealth.com
Investigator:
Last name:
Emily K. Curran
Email:
Principal Investigator
Facility:
Name:
University of Oklahoma Health Sciences Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
405-271-8777
Email:
ou-clinical-trials@ouhsc.edu
Investigator:
Last name:
Manu Pandey
Email:
Principal Investigator
Facility:
Name:
University of Pittsburgh Cancer Institute (UPCI)
Address:
City:
Pittsburgh
Zip:
15232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
412-647-8073
Investigator:
Last name:
Annie P. Im
Email:
Principal Investigator
Facility:
Name:
Huntsman Cancer Institute/University of Utah
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
888-424-2100
Email:
cancerinfo@hci.utah.edu
Investigator:
Last name:
Ami Patel
Email:
Principal Investigator
Facility:
Name:
University of Virginia Cancer Center
Address:
City:
Charlottesville
Zip:
22908
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
434-243-6303
Email:
uvacancertrials@hscmail.mcc.virginia.edu
Investigator:
Last name:
Daniel R. Reed
Email:
Principal Investigator
Facility:
Name:
Virginia Commonwealth University/Massey Cancer Center
Address:
City:
Richmond
Zip:
23298
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Email:
CTOclinops@vcu.edu
Investigator:
Last name:
Keri R. Maher
Email:
Principal Investigator
Facility:
Name:
University Health Network-Princess Margaret Hospital
Address:
City:
Toronto
Zip:
M5G 2M9
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
416-946-4501
Email:
clinical.trials@uhn.on.ca
Investigator:
Last name:
Marta Davidson
Email:
Principal Investigator
Start date:
June 27, 2023
Completion date:
August 31, 2025
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05600894
