Advanced Chronic Myeloid LeukemiaPhase 1NCT06401603
A Phase I Study of Decitabine, Lisaftoclax, and Olverembatinib in Patients With Advanced Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Myeloid Leukemia
A Phase 1 study testing Decitabine, Listaftoclax and Olverembatinib in people with Advanced Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Chronic Myeloid Leukemia, Philadelphia Chromosome-Positive Acute Myeloid Leukemia
- What is being tested?
- Decitabine, Listaftoclax and Olverembatinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Aug 2024to 1 Jan 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3 x ULN, unless due to the underlying leukemia approved by the PI
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- Creatinine clearance ≥30 mL/min
- 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.
Who cannot join
- Participants who have previously received lisaftoclax or olverembatinib
- History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
- Active grade III-V cardiac failure as defined by the New York Heart Association Criteria
- Clinically significant and uncontrolled cardiovascular disease, including but not restricted to:
- Myocardial infarction (MI), stroke, revascularization, unstable angina, or transient ischemic attack within 6 months.
- Left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards prior to enrollment.
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- 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.
- Prolonged QTc interval on pre-entry electrocardiogram (> 480 msec) unless corrected after electrolyte replacement.
- 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; and systolic >150mmHg).
- Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment).
- Active central nervous system leukemia
- Known human immunodeficiency virus (HIV) seropositive, unless well-controlled on stable doses of anti-retroviral therapy.
- 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.
- 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
- 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
- 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.
- Inability to swallow
- Pregnant or breastfeeding women will not be eligible
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Decitabine, Lisaftoclax, and Olverembatinib or other agents used in study.
- Participants with psychiatric illness/social situations that would limit compliance with study requirements.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Nicholas Short, MD, 713-563-4485, nshort@mdanderson.org
Nicholas Short, MD
About this study
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.
Read the 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).
- Conditions
- Advanced Chronic Myeloid Leukemia, Philadelphia Chromosome-Positive Acute Myeloid Leukemia
- Being tested
- Decitabine, Listaftoclax, Olverembatinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Also called Dacogen
Given by IV
ListaftoclaxDrug
Given by PO
OlverembatinibDrug
Given by PO
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 | Experimental | Participants enrolled in Phase I, the dose of lisaftoclax you receive will depend on when a participants join this study. Up to 2 dose levels of lisaftoclax will be tested. Between 3-12 participants will be enrolled at each dose level. Receives: Drug: Decitabine; Drug: Listaftoclax; Drug: Olverembatinib |
| Phase 2 | Experimental | Participants enrolled in Phase II, participants will receive lisaftoclax at the recommended dose that was found in Phase I Receives: Drug: Decitabine; Drug: Listaftoclax; Drug: Olverembatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and adverse events (AEs)
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2024
- Study start6 Aug 2024
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Ascentage Pharma Group Inc.
- Responsible party
- Sponsor
- Investigators
- Nicholas Short, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06401603
- Sponsor's protocol ID
- 2024-0032
- Other IDs
- NCI-2024-03867
- Status last verified
- Sep 2026
- First submitted
- 2 May 2024
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Decitabine, Lisaftoclax, and Olverembatinib in Patients With Advanced Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT06401603
- Acronym / sponsor ID
- 2024-0032
- Conditions
- Advanced Chronic Myeloid Leukemia, Philadelphia Chromosome-Positive Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Ascentage Pharma Group Inc.
- Study start
- 6 Aug 2024 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2029 (estimated)
- First posted
- 6 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 | Experimental | Drug: Decitabine, Drug: Listaftoclax, Drug: OlverembatinibParticipants enrolled in Phase I, the dose of lisaftoclax you receive will depend on when a participants join this study. Up to 2 dose levels of lisaftoclax will be tested. Between 3-12 participants will be enrolled at each dose level. |
| Phase 2 | Experimental | Drug: Decitabine, Drug: Listaftoclax, Drug: OlverembatinibParticipants enrolled in Phase II, participants will receive lisaftoclax at the recommended dose that was found in Phase I |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- 4. Ability to understand and the willingness to sign a written informed consent document
Key exclusion criteria (20 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DecitabineAlso: DacogenGiven by IV | Drug | Phase 1, Phase 2 |
| ListaftoclaxGiven by PO | Drug | Phase 1, Phase 2 |
| OlverembatinibGiven by PO | Drug | Phase 1, Phase 2 |
Primary outcome
Safety and adverse events (AEs)
Time frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nicholas Short, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Decitabine, Listaftoclax and Olverembatinib in people with Advanced Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nicholas Short, MD ((713) 563-4485, nshort@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and adverse events (AEs) (time frame: Through study completion; an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.