Trial Title:
A Phase I Study of Decitabine, Lisaftoclax, and Olverembatinib in Patients With Advanced Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Myeloid Leukemia
NCT ID:
NCT06401603
Condition:
Advanced Chronic Myeloid Leukemia
Philadelphia Chromosome-Positive Acute Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Philadelphia Chromosome
Decitabine
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Decitabine
Description:
Given by IV
Arm group label:
Phase 1
Arm group label:
Phase 2
Other name:
Dacogen
Intervention type:
Drug
Intervention name:
Listaftoclax
Description:
Given by PO
Arm group label:
Phase 1
Arm group label:
Phase 2
Intervention type:
Drug
Intervention name:
Olverembatinib
Description:
Given by PO
Arm group label:
Phase 1
Arm group label:
Phase 2
Summary:
To find the recommended doses of lisaftoclax and olverembatinib that can be given in
combination with decitabine to participants with advanced CML and Ph+ AML.
Detailed description:
Primary Objectives
• To establish the minimum safe and biologically-effective dose of lisaftoclax and
olverembatinib in combination with decitabine
Secondary Objectives
- To determine the rate of conversion to CML-CP for participants with advanced phase
CML or complete remission (CR)/CR with incomplete hematology recovery (CRi) for
participants with Ph+ AML, within 4 cycles of combination therapy
- To assess other efficacy endpoints (CR rate, measurable residual disease negativity
by flow cytometry, rates of CCyR, MMR, MR4 and MR4.5, relapse-free survival, overall
survival)
- To assess proportion of participants proceeding to allogeneic hematopoietic stem
cell transplantation
- To determine the safety of the combination regimen
Exploratory Objectives
- To evaluate the impact of olverembatinib monotherapy on signaling pathways and
apoptotic protein expression
- To assess relationship between baseline signaling pathway activation and apoptotic
protein expression on response and long-term outcomes such as overall survival (OS)
and relapse free survival (RFS).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
a) Diagnosis: Age ≥18 years with CML-AP, CML-MBP, or Ph+ AML by WHO 2016 criteria.
- Participants must have been intolerant or resistant to at least one prior BCR::ABL1
TKI
2. Performance status ≤3 (ECOG Scale).
3. Adequate liver, cardiac, renal and pancreatic function as defined by the
following criteria:
1. Total serum bilirubin < 1.5 x upper limit of normal (ULN), unless due to
Gilbert's syndrome, hemolysis or the underlying leukemia approved by the PI
2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3 x ULN,
unless due to the underlying leukemia approved by the PI
3. Creatinine clearance ≥30 mL/min
4. Serum amylase or lipase < 1.5 x ULN
4. Ability to understand and the willingness to sign a written informed
consent document
5. Willingness to use adequate contraception prior to study entry, for the
duration of study participation, and for 6 months after completion of
study participation. For women of child-bearing potential, adequate
methods of contraception include: complete abstinence,, hormonal
contraception (i.e. birth control pills, injection, implant, transdermal
patch, vaginal ring), intrauterine device (IUD), tubal Ligation or
hysterectomy, subject/partner post vasectomy, implantable or injectable
contraceptives, and condoms plus spermicide.
Exclusion Criteria:
1. Participants who have previously received lisaftoclax or olverembatinib
2. History of acute pancreatitis within 1 year of study or history of chronic
pancreatitis
3. Active grade III-V cardiac failure as defined by the New York Heart
Association Criteria
4. Clinically significant and uncontrolled cardiovascular disease, including
but not restricted to:
i. Myocardial infarction (MI), stroke, revascularization, unstable angina,
or transient ischemic attack within 6 months.
ii. Left ventricular ejection fraction (LVEF) less than lower limit of
normal per local institutional standards prior to enrollment.
iii. Diagnosed or suspected congenital long QT syndrome. iv. Clinically
significant atrial or ventricular arrhythmias (such as uncontrolled,
clinically significant atrial fibrillation, ventricular tachycardia,
ventricular fibrillation, or Torsades de pointes) as determined by the
treating physician.
v. Prolonged QTc interval on pre-entry electrocardiogram (> 480 msec)
unless corrected after electrolyte replacement.
vi. History of venous thromboembolism including deep venous thrombosis or
pulmonary embolism within the past 3 months, excluding line associated DVT
of the upper extremity vii. Uncontrolled hypertension (diastolic blood
pressure >100mmHg; systolic >150mmHg).
5. Active serious infection not controlled by oral or intravenous antibiotics
(e.g. persistent fever or lack of improvement despite antimicrobial
treatment).
6. Active central nervous system leukemia
7. Known human immunodeficiency virus (HIV) seropositive, unless
well-controlled on stable doses of anti-retroviral therapy.
8. Known hepatitis B surface antigen seropositive or known or suspected
active hepatitis C infection Note: Participants who have isolated positive
hepatitis B core antibody (ie, in the setting of negative hepatitis B
surface antigen and negative hepatitis B surface antibody) must have an
undetectable hepatitis B viral load. Participants who have positive
hepatitis C antibody may be included if they have an undetectable
hepatitis C viral load.
9. Participants with a prior or concurrent malignancy whose natural history
or treatment is not anticipated to interfere with the safety or efficacy
assessment of the investigational regimen may be included only after
discussion with the PI
10. Consumed strong inducer of CYP3A or p-glycoprotein within 14 days of study
enrollment, or 5 half-lives, whichever is longer. Agents include but are
not limited to: carbamazepine, phenytoin, rifampin, and St. John's wart
11. Treatment with any investigational antileukemic agents or chemotherapy
agents in the last 7 days before study entry, unless full recovery from
side effects has occurred or patient has rapidly progressive disease
judged to be life-threatening by the investigator. Prior recent treatment
with corticosteroids, hydroxyurea, cytarabine (up to 2 g/m2 given for
cytoreduction within the preceding 7 days) and/or an FDA-approved
BCR::ABL1 TKI is permitted.
12. Inability to swallow
13. Pregnant or breastfeeding women will not be eligible
14. History of allergic reactions attributed to compounds of similar chemical
or biologic composition to Decitabine, Lisaftoclax, and Olverembatinib or
other agents used in study.
15. Participants with psychiatric illness/social situations that would limit
compliance with study requirements.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nicholas Short, MD
Phone:
713-563-4485
Email:
nshort@mdanderson.org
Investigator:
Last name:
Nicholas Short, MD
Email:
Principal Investigator
Start date:
August 6, 2024
Completion date:
January 1, 2029
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Collaborator:
Agency:
Ascentage Pharma Group Inc.
Agency class:
Industry
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06401603
http://www.mdanderson.org
