Trial Title:
A Study Comparing Venetoclax and Azacitidine Plus Cusatuzumab to Venetoclax and Azacitidine in Newly Diagnosed AML Ineligible for Intensive Therapy
NCT ID:
NCT06384261
Condition:
Leukemia, Myeloid, Acute
Conditions: Official terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Azacitidine
Venetoclax
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cusatuzumab
Description:
CD70 monoclonal antibody
Arm group label:
Cusatuzumab in combination with venetoclax and azacitidine
Other name:
OV-1001
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
BCL-2 inhibitor
Arm group label:
Cusatuzumab in combination with venetoclax and azacitidine
Arm group label:
Venetoclax in combination with azacitidine
Intervention type:
Drug
Intervention name:
Azacitidine
Description:
Hypomethylating agent
Arm group label:
Cusatuzumab in combination with venetoclax and azacitidine
Arm group label:
Venetoclax in combination with azacitidine
Summary:
The goal of this clinical trial is to learn if participants treated with the experimental
drug cusatuzumab added to venetoclax and azacitidine works to treat acute myeloid
leukemia (AML) compared to venetoclax and azacitidine. Venetoclax and azacitidine are
drugs commonly used to treat AML in patients that are unable to receive chemotherapy to
treat AML. The main question the clinical trial aims to answer is does cusatuzumab added
to venetoclax and azacitidine prolong the length of time participants live compared to
venetoclax and azacitidine?
Detailed description:
This is a randomized, open-label, multicenter, Phase 2 trial to evaluate the efficacy,
safety, and pharmacodynamics of cusatuzumab in combination with venetoclax and
azacitidine compared to venetoclax and azacitidine in persons with newly diagnosed AML
who are deemed ineligible for intensive chemotherapy.
Potential participants will be considered ineligible for intensive chemotherapy and,
therefore, eligible for the study, if they meet the trial eligibility criteria. Potential
participants will undergo a diagnostic bone marrow biopsy and aspirate collected for
pathology review, cytogenetics, fluorescence in situ hybridization (FISH), and polymerase
chain reaction (PCR) analysis and other studies for confirmation of a diagnosis of AML
and to define whether participants have adverse, intermediate, or favorable AML risk
features.
The enrolled trial population will be enriched for participants with adverse risk
features by enrolling adverse, intermediate, and favorable risk participants at a ratio
of 3:1:1, respectively (i.e., 72 adverse risk, 24 intermediate risk, and 24 favorable
risk participants will be enrolled). Enrolled participants will then be randomized 2:1 to
either the experimental arm or the active comparator arm.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Men and women ≥18 years old
- Must sign an informed consent form (ICF) indicating that he or she understands the
purpose of, and procedures required for the study and is willing to participate in
the study
- Diagnosis of AML according to ICC 2022 (with the exclusion of MDS/AML with 10-19%
blasts)
- Previously untreated AML except may have received emergency leukapheresis,
hydroxyurea before study entry to control hyperleukocytosis
- Deemed unfit for intensive chemotherapy by meeting at least 1 of the following
criteria:
1. Participant is ≥75 years of age with Eastern Cooperative Oncology Group (ECOG)
performance status of 0 to 2 OR
2. Participant is ≥18 to 74 years of age and has any of the following
comorbidities:
1. ECOG performance status of 2 or 3
2. Cardiac status including any one of the following: congestive heart
failure requiring treatment or ejection fraction ≤50% or chronic stable
angina
3. Known history of diffusion capacity of lung for carbon monoxide (DLCO)
≤65% of forced expiratory volume in the first second (FEV1) ≤65%
4. Creatinine clearance (CrCl) ≥15 mL/min to <45 mL/min
5. Hepatic disorder with total bilirubin >1.5 to 3x the upper limit of normal
(ULN)
6. Any other comorbidity that the investigators determine to be incompatible
with conventional intensive chemotherapy
- Adequate liver and renal function defined as:
1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3xULN; for
participants with leukemic infiltration of the liver (documented by biopsy or
imaging), AST and ALT <5xULN is permitted
2. Total bilirubin ≤1.5xULN, unless bilirubin rise is due to Gilbert's syndrome or
of nonhepatic origin. Participants who are <75 years of age may have a
bilirubin up to 3xULN.
3. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 (by the
Modification of Diet in Renal Disease [MDRD] formula). Participants who are <75
years of age may have an eGFR ≥15 mL/min/1.73 m2.
- Women of childbearing potential (WOCBP), defined as fertile women between menarche
and post menopause unless permanently sterile, must have a negative highly sensitive
serum β-human chorionic gonadotropin (β-hCG) or urine pregnancy test at screening
- Must be willing to use contraception as consistent with institutional guidelines
regarding the use of contraceptive methods for participants participating in
clinical studies
1. WOCBP must agree to adhere to the following birth control measures while
receiving study treatment continuing to 3 months after the last dose of study
drug:
1. Must be practicing a highly effective method of birth control (failure
rate of <1% per year when used consistently and correctly) as determined
by institutional standards
2. Must agree to not donate eggs (ova, oocytes) for the purposes of assisted
reproduction
3. Must not be breastfeeding and not planning to become pregnant
2. Male participants who are sexually active with WOCBP, and male partners of
study participants who are WOCBP, and who are not surgically or otherwise
sterile must agree to adhere to the following birth control measures while
receiving study treatment and for 3 months after the last dose of study drug:
1. Must agree to use a barrier method of birth control (e.g., either condom
with spermicidal foam/gel/film/cream/suppository or partner with occlusive
cap [diaphragm or cervical/vault caps] with spermicidal foam, gel, film,
cream, or suppository)
2. Must not donate sperm
3. Must no plan to father a child
- Participants with HIV infection are eligible for the trial if the following criteria
are met:
1. CD4+ T-cell count ≥200 cells/μL
2. No prior history of AIDS-defining opportunistic infection within the past 12
months
3. Receiving treatment with antiretroviral therapy
4. Undetectable viral load within 6 months of screening
Exclusion Criteria:
- Any prior treatment for AML (except those outlined in inclusion criterion #4)
- Participant has received a hypomethylating agent (HMA) or venetoclax for MDS or
myeloproliferative neoplasm
- Leukemic involvement in the central nervous system
- Participants with acute promyelocytic leukemia (APL)
- ECOG performance status of 4 for participants 18 to 74 years of age and ECOG
performance status of 3 or 4 for participants ≥75 years of age
- Use of immune suppressive agents ≤4 weeks before the first administration of
cusatuzumab. Participants may be included if free of systemic corticosteroids >5
days before the first administration of cusatuzumab with the exception of
corticosteroids at physiologic replacement doses.
- Received a live, attenuated vaccine within 4 weeks prior to initiation of study drug
- Active malignancies (i.e., progressing or requiring treatment change in the last 24
months) other than the disease being treated under study. Exceptions to this
exclusion criterion include the following:
1. Nonmelanoma skin cancer treated within the last 24 months that is considered
completely cured
2. Adequately treated breast lobular carcinoma in situ and breast ductal carcinoma
in situ
3. Adequately treated cervical carcinoma in situ and breast ductal carcinoma in
situ
4. History of localized breast cancer and receiving anti-hormonal agents, or
history of localized prostate cancer (N0M0) and receiving androgen depravation
therapy
5. A malignancy that is considered cured with minimal risk of recurrence
- Any active systemic infection
- History of prior HSCT (allogeneic or autologous transplants)
- Active hepatitis B or C infection or other clinically active liver diseases ad
defined below:
1. Seropositivity for hepatitis B is defined by a positive test for hepatitis B
surface antigen (HBsAg)
2. Participants with resolved infection (i.e., participants who are HBsAg negative
with antibodies to total hepatitis B core antigen [anti-HBc] with or without
the presence of hepatitis B surface antibody [anti-HBs]) must be screened using
PCR measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR
positive will be excluded.
- Participants with serologic findings suggestive of HBV vaccination
(anti-HBs positivity as the only serologic marker) AND a known history of
prior HBV vaccination, do not need to be tested for HBV DNA by PCR
3. Active hepatitis C infection as defined by being positive for a nucleic acid
test for hepatitis C virus (HCV) RNA
- Congestive hear failure severity that is New York Heart Association Class III or IV
- Unstable angina
- Known allergies, hypersensitivity, or intolerance to cusatuzumab, venetoclax, or
azacitidine or their excipients (e.g., mannitol, an excipient of azacitidine)
- Inability or difficulty swallowing capsules/tablets, malabsorption syndrome, or any
disease or medical condition significantly affecting gastrointestinal function
- Any condition for which, in the investigator's opinion, participation would not be
in the best interest of the participant (e.g., compromise the well-being) or
physical limitations that could prevent, limit, or confound the protocol-specified
assessments
- Major surgery (e.g., requiring general anesthesia) ≤4 weeks prior to initiation of
study treatment
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Banner MD Anderson
Address:
City:
Gilbert
Zip:
85234
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
City of Hope
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ahmed Aribi, M.D.
Phone:
877-467-3411
Email:
aaribi@coh.org
Contact backup:
Last name:
Ahmed Aribi, M.D.
Facility:
Name:
University of California Los Angeles
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
University of Colorado Health - Anschutz Cancer Pavilion - Anschutz Medical Campus
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
AdventHealth Medical Group Blood & Marrow Transplant at Orlando
Address:
City:
Orlando
Zip:
32804
Country:
United States
Status:
Recruiting
Contact:
Last name:
Advent Health Oncology Research
Phone:
407-303-2090
Email:
CFD.ResearchOncology@AdventHealth.com
Contact backup:
Last name:
Shahram Mori, MD, PhD
Facility:
Name:
University of Kentucky Chandler Medical Center
Address:
City:
Lexington
Zip:
40536
Country:
United States
Status:
Recruiting
Contact:
Last name:
Lauren Cardany
Phone:
859-218-7295
Email:
Lnmann3@uky.edu
Contact backup:
Last name:
Ayman Qasrawi, MD
Facility:
Name:
Norton Healthcare, Inc.
Address:
City:
Louisville
Zip:
40202
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rachel Mattingly, MSN
Phone:
502-899-3366
Phone ext:
19307
Email:
leukemia-nciresearch@nortonhealthcare.org
Contact backup:
Last name:
Don Stevens, MD
Facility:
Name:
Hackensack University Medical Center
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Hofstra/Northwell Health
Address:
City:
Lake Success
Zip:
11042
Country:
United States
Status:
Recruiting
Contact:
Last name:
Dina Padula
Phone:
516-734-3579
Email:
dpadula1@northwell.edu
Contact backup:
Last name:
David Chitty, DO, MSc
Facility:
Name:
Cornell University
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
University of Rochester Medical Center
Address:
City:
Rochester
Zip:
14642
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Novant Health
Address:
City:
Charlotte
Zip:
28204
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Wake Forest North Carolina
Address:
City:
Winston-Salem
Zip:
27157
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Wake Forest University Health Sciences
Address:
City:
Winston-Salem
Zip:
27157
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Cleveland Clinic - Taussig Cancer Institute
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Medical University of South Carolina
Address:
City:
Charleston
Zip:
29425
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Fred Hutch Seattle Cancer Care Alliance
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Medical College of Wisonsin
Address:
City:
Milwaukee
Zip:
53226
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Sameem Abedin, MD
Facility:
Name:
Marien Hospital Duesseldorf
Address:
City:
Dusseldorf
Zip:
40479
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Vera Lohrbacher
Phone:
49 211 4400 2079
Email:
MHD-Studien@vkkd-kliniken.de
Contact backup:
Last name:
Aristoteles Giagounidis, MD
Facility:
Name:
Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre
Address:
City:
Vancouver
Zip:
V5Z 1M9
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Madeleine Cannings
Phone:
XXXXXXXXXX
Email:
madeleine.cannings@bccancer.bc.ca
Contact backup:
Last name:
Ryan Stubbins, MD, FRCPC
Facility:
Name:
HFR Fribourg - Hopital Cantonal
Address:
City:
Fribourg
Zip:
Switzerland
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Anna Efthymiou
Phone:
41 026 306 23 33
Email:
anna.efthymiou@h-fr.ch
Contact backup:
Last name:
Anna Efthymiou
Start date:
July 22, 2024
Completion date:
June 2027
Lead sponsor:
Agency:
OncoVerity, Inc.
Agency class:
Industry
Source:
OncoVerity, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06384261
