Acute Myeloid LeukemiaPhase 1NCT05834244
A Phase Ib Trial of Azacitidine, Venetoclax and Allogeneic NK Cells for Acute Myeloid Leukemia (ADVENT-AML)
A Phase 1 study testing Azacitidine, Venetoclax and NK Cells in people with Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 2 sites in United States.
Trial summary
To learn if adding a healthy person's natural killer (NK) cells to the combination of Azacitidine and Venetoclax can help to control AML. NK cells are cancer- and infection-fighting immune cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Azacitidine, Venetoclax and NK Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 2 sitesUnited States
- Study dates
- 26 Oct 2023to 30 Jun 2028
- 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
- Patients need to have a confirmed diagnosis of AML, or MDS/AML with 10% to 19% blasts, per the International Consensus Classification 2022 or the WHO 2022 classification.43,44
- Dose escalation cohort:
- Patients ≥18 years with R/R AML or R/R MDS/AML, other than acute promyelocytic leukemia (APL), or core binding factor (CBF) AML with no available standard treatment options.
- Relapsed or refractory disease defined by standard criteria as follows
- Relapsed: Bone marrow blasts ≥5%, reappearance of blasts in the blood, or development of extramedullary disease following achievement of CR/CRi/MLFS
- Refractory: Failure to achieve CR/CRi/MLFS following initial treatment, with evidence of persistent leukemia by blood and/or bone marrow evaluation
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- Appropriate prior therapy in order for patient to be deemed relapsed or refractory include the following
- 7+3 based induction: 2 cycles of for patients <60 years, and 1 cycle for patients who are either ≥60 years or unfit for intensive therapy ii. 1 cycle of induction regimen containing intermediate dose or higher of cytarabine iii. 2 cycles of venetoclax with HMA/LDAC +/- other agents iv. 4 cycles of HMA alone d. For patients in first relapse, the dose escalation cohort will only enroll patients in early first relapse, i.e., first remission duration of ≤12 months.
- Patients relapsing after allo-SCT may be eligible if they have recovered from all transplant-related toxicities and are off all immunosuppression, with no more than grade 1 chronic GVHD. Physiologic dose of steroids (≤10 mg prednisone or equivalent) may be acceptable.
- Patients with actionable mutations with available FDA-approved therapies, e.g., FLT3, IDH1/2 inhibitors may be enrolled after they have exhausted such available FDA approved treatment options.
- Dose expansion cohort:
- Dose expansion cohort will only enroll older/unfit patients with newly diagnosed adverse or intermediate risk AML or MDS/AML who are ineligible for intensive chemotherapy and/or are ineligible for or decline to receive allo-SCT (please refer to stratification in statistics section).
- Adverse risk AML or MDS/AML defined per AML ELN 2022 recommendations.
- Age ≥ 75 years, or
- Age ≥ 18 years with at least one of the following comorbidities
- ECOG PS 2 or 3
- Left ventricular ejection fraction (LVEF) ≤ 50%
- Lung diffusing capacity for carbon monoxide (DLCO) ≤ 65% of expected
- Forced expiratory volume in 1 second (FEV1) ≤ 65% of expected
- Chronic stable angina or congestive heart failure controlled with medication
- Other comorbidity or conditions that the Investigator judges as incompatible with intensive chemotherapy, or allo-SCT which must be documented
- Patients with antecedent aplastic anemia, myelodysplastic syndrome, or chronic myelomonocytic leukemia may be eligible if they had not received prior hypomethylating agent, BCL2 inhibitors, MCL1 inhibitors, chemotherapy (definitive or therapeutic intent), or allo-SCT for MDS. Acceptable prior therapies include erythropoietin stimulating agents, thrombopoietin receptor agonists, lenalidomide, luspatarcept, anti-thymocyte globulin, cyclosporine, and iron chelating agents.
- All patients:
- Adequate hepatic function (direct bilirubin ≤ 2 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT ≤ 2.5 x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT ≤ 3 x ULN will be considered eligible.)
- Adequate renal function with creatinine clearance ≥ 30 mL/min calculated by the Cockcroft- Gault formula or measured by 24-hour urine collection
- The effects of these agents on the developing human fetus are unknown. For this reason, and because other therapeutic agents used in this trial may be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 90 days after last treatment. This includes all female patients between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
- Postmenopausal (no menses in greater than or equal to 12 consecutive months).
- History of hysterectomy or bilateral salpingo-oophorectomy.
- Ovarian failure (follicle-stimulating hormone and estradiol in menopausal range, who have received whole pelvic radiation therapy).
- History of bilateral tubal ligation or another surgical sterilization procedure.
- Approved methods of birth control are as follows: 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. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. 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 prior to the study, for the duration of study participation, and 4 months after completion of treatment.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients with t(15;17), t(8;21), inv(16), or t(16;16) karyotypic abnormality
- Patient has a white blood cell count > 15 x 10⁹/L. Hydroxyurea, and/or cytarabine (up to 2 g/m2 total) used as supportive care is permitted to meet this criterion.
- Patients who have received high-dose (e.g., > 10 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 1 week or 5 half-lives of first NK cell infusion date (cycle 1 Day 8), whichever is longer.
- Patients with known symptomatic or uncontrolled CNS leukemia.
- Patient has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate treatment.
- Any signs or symptoms of active CNS pathology within 6 months of screening including history of seizures requiring anti-epileptics, focal neurological deficit, stroke, dementia, brain injury, or organic brain pathology. Any subarachnoid hemorrhage or CNS bleed within 3 months of screening.
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- Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications as determined by the investigator.
- Active and uncontrolled comorbidities including decompensated congestive heart failure NYHA class III/IV, clinically significant and uncontrolled arrhythmia as judged by the treating physician.
- Known active hepatitis B (HBV) or Hepatitis C (HCV) infection with detectable viral DNA or RNA, respectively, or known HIV infection.
- Corrected QT interval (QTc) > 480 msec or history of Torsades de pointes
- Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator.
- Any previous or concomitant malignancy, except when the patient has completed definitive curative-intent treatment with chemotherapy and/or surgery and/or radiotherapy at least 3 months prior to enrollment. Patients having completed definitive treatment for the following conditions may be eligible immediately after completion of definitive curative-intent therapy, after healing of wounds, and no evidence of residual disease by examination, imaging, and/or cytology/pathology, e.g., non-melanoma skin cancers, or a carcinoma in-situ, e.g., ductal carcinoma in situ, urothelial cancer, cervical cancer, localized prostate cancer, pre-cancerous colon polyp, etc.
- Weight <50 kg
- Major surgery within 4 weeks prior to screening or a major wound that has not fully healed.
- Patients under legal protection measure (guardianship, trusteeship or safeguard of justice) and/or uncontrolled psychiatric comorbidities, ongoing illicit substance abuse, inability, any impairment or unwillingness to comply with the treatments, follow-up, requirements and procedures of this clinical trial.
- A known hypersensitivity or severe allergy to study drug components or diluents
- Nursing women, women of childbearing potential (WOCBP) with positive urine or serum pregnancy test, or WOCBP who are not willing to maintain adequate contraception.
- Pregnant women are excluded from this study because study agents may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with study agents, breastfeeding should be discontinued if the mother is treated on this study.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Case Western Reserve University
Cleveland, Ohio, 44106
Benjamin Tomlinson, MD, benjamin.tomlinson@uhhospitals.org
Benjamin Tomlinson, MD
- Recruiting
M.D. Anderson Cancer Center
Houston, Texas, 77030
Abhishek Maiti, MD, 713-792-7305, amaiti@mdanderson.org
Abhishek Maiti, MD
About this study
To learn if adding a healthy person's natural killer (NK) cells to the combination of Azacitidine and Venetoclax can help to control AML. NK cells are cancer- and infection-fighting immune cells.
Read the detailed description
Primary Objective:
-To evaluate Safety of the combination of azacitidine, venetoclax and allogeneic NK cells
Secondary Objective:
- To estimate overall response rate (ORR)
- To estimate rate of CR/CRi by 4 cycles of therapy
- To estimate rate of MRD negative by 6 cycles
- To estimate overall survival (OS)
- To estimate relapse-free survival (RFS)
Exploratory Objectives:
- To estimate rate of CRc MRD negative at any time
- To estimate event-free survival (EFS)
- To estimate duration of response (DOR)
- To estimate median time to blood count recovery
- To estimate median time to first response
- To estimate median time to negative MRD
- To evaluate persistence of NK cells in peripheral blood
- To explore biomarker of response and resistance
- Using propensity-score matching analysis (per post-hoc plan) to explore the difference in response, survival adverse events in contemporary historical control population treated with HMA-VEN
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Azacitidine, Venetoclax, NK Cells
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5-azacytidine, 5-aza, Vidaza™, 5-AZC
Given by IV (vein)
VenetoclaxDrug
Also called ABT-199, GDC-0199
Given by PO
NK CellsDrug
Given by IV (vein)
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | Dose Escalation to evaluate the combination of azacitidine, venetoclax and allogeneic NK cells in older/unfit participants with AML ineligible for intensive chemotherapy or allogeneic stem-cell transplantation (allo SCT). Receives: Drug: Azacitidine; Drug: Venetoclax; Drug: NK Cells |
| Dose Expansion | Experimental | Dose Expansion to evaluate the combination of azacitidine, venetoclax and allogeneic NK cells in older/unfit participants with AML ineligible for intensive chemotherapy or allogeneic stem-cell transplantation (allo SCT). Receives: Drug: Azacitidine; Drug: Venetoclax; Drug: NK Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 posted28 Apr 2023
- Study start26 Oct 2023
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute 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
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Abhishek Maiti, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05834244
- Sponsor's protocol ID
- 2022-0941
- Other IDs
- NCI-2023-03179
- Status last verified
- Jun 2026
- First submitted
- 12 Apr 2023
- Last updated
- 12 Jun 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 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Trial of Azacitidine, Venetoclax and Allogeneic NK Cells for Acute Myeloid Leukemia (ADVENT-AML)
- ClinicalTrials.gov ID
- NCT05834244
- Acronym / sponsor ID
- 2022-0941
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 26 Oct 2023 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 28 Apr 2023 (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 learn if adding a healthy person's natural killer (NK) cells to the combination of Azacitidine and Venetoclax can help to control AML. NK cells are cancer- and infection-fighting immune cells.
Detailed description
Primary Objective:
-To evaluate Safety of the combination of azacitidine, venetoclax and allogeneic NK cells
Secondary Objective:
- To estimate overall response rate (ORR)
- To estimate rate of CR/CRi by 4 cycles of therapy
- To estimate rate of MRD negative by 6 cycles
- To estimate overall survival (OS)
- To estimate relapse-free survival (RFS)
Exploratory Objectives:
- To estimate rate of CRc MRD negative at any time
- To estimate event-free survival (EFS)
- To estimate duration of response (DOR)
- To estimate median time to blood count recovery
- To estimate median time to first response
- To estimate median time to negative MRD
- To evaluate persistence of NK cells in peripheral blood
- To explore biomarker of response and resistance
- Using propensity-score matching analysis (per post-hoc plan) to explore the difference in response, survival adverse events in contemporary historical control population treated with HMA-VEN
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Drug: Azacitidine, Drug: Venetoclax, Drug: NK CellsDose Escalation to evaluate the combination of azacitidine, venetoclax and allogeneic NK cells in older/unfit participants with AML ineligible for intensive chemotherapy or allogeneic stem-cell transplantation (allo SCT). |
| Dose Expansion | Experimental | Drug: Azacitidine, Drug: Venetoclax, Drug: NK CellsDose Expansion to evaluate the combination of azacitidine, venetoclax and allogeneic NK cells in older/unfit participants with AML ineligible for intensive chemotherapy or allogeneic stem-cell transplantation (allo SCT). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- Patients need to have a confirmed diagnosis of AML, or MDS/AML with 10% to 19% blasts, per the International Consensus Classification 2022 or the WHO 2022 classification.43,44
- Patients ≥18 years with R/R AML or R/R MDS/AML, other than acute promyelocytic leukemia (APL), or core binding factor (CBF) AML with no available standard treatment options.
- Relapsed or refractory disease defined by standard criteria as follows
- Patients relapsing after allo-SCT may be eligible if they have recovered from all transplant-related toxicities and are off all immunosuppression, with no more than grade 1 chronic GVHD. Physiologic dose of steroids (≤10 mg prednisone or equivalent) may be acceptable.
- Patients with actionable mutations with available FDA-approved therapies, e.g., FLT3, IDH1/2 inhibitors may be enrolled after they have exhausted such available FDA approved treatment options.
Key exclusion criteria (18 listed)
- Patients with t(15;17), t(8;21), inv(16), or t(16;16) karyotypic abnormality
- Patient has a white blood cell count > 15 x 10⁹/L. Hydroxyurea, and/or cytarabine (up to 2 g/m2 total) used as supportive care is permitted to meet this criterion.
- Patients who have received high-dose (e.g., > 10 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 1 week or 5 half-lives of first NK cell infusion date (cycle 1 Day 8), whichever is longer.
- Patients with known symptomatic or uncontrolled CNS leukemia.
- Patient has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate treatment.
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 |
|---|---|---|
| AzacitidineAlso: 5-azacytidine, 5-aza, Vidaza™, 5-AZCGiven by IV (vein) | Drug | Dose Escalation, Dose Expansion |
| VenetoclaxAlso: ABT-199, GDC-0199Given by PO | Drug | Dose Escalation, Dose Expansion |
| NK CellsGiven by IV (vein) | Drug | Dose Escalation, Dose Expansion |
Primary outcome
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Time frame: Through study completion; an average of 1 year
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 12 Jun 2026.
- M D 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.
Abhishek Maiti, MD principal investigator
M.D. Anderson Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Azacitidine, Venetoclax and NK Cells in people with Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 2 sites 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 33 inclusion and 18 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 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 Abhishek Maiti, MD (713-792-7305, amaiti@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 (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 12 Jun 2026.