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New treatment option for Acute Myeloid Leukemia
Official title A Phase Ib Trial of Azacitidine, Venetoclax and Allogeneic NK Cells for Acute Myeloid Leukemia (ADVENT-AML)
ClinicalTrials.gov ID: NCT05834244
What this study is testing
What is Azacitidine?
Azacitidine is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for acute myeloid leukemia.
Also referred to as 5-azacytidine, 5-aza.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- 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...
- 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...
- 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
You likely can't join if
- 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...
- Patients who have received high-dose (e.g., \> 10 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive...
- 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...
- Any signs or symptoms of active CNS pathology within 6 months of screening including history of seizures requiring anti-epileptics, focal...
See the full eligibility criteria
Who can 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
- Appropriate prior therapy in order for patient to be deemed relapsed or refractory include the following i. 7+3 based induction: 2 cycles of for patients \<60 years, and 1 cycle for patients who are either ≥60 years or...
- 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...
- 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...
- 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...
- 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...
- 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...
- 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...
- 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.
What rules you out
- 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...
- 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...
- 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...
- 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...
- 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...
The study team makes the final eligibility decision.
Where it's taking place
- Cleveland, Ohio, United States
- Houston, Texas, United States
Compensation & support
A stipend or compensation may be offered.
Compensation mentioned.
ClinicalTrials.gov doesn't provide a reliable structured field for payment or travel support - confirm details with the study team.
Questions & answers
Do participants get paid in this trial?
This study's listing includes signals that participants may be compensated or receive a stipend. Amounts vary and are set by the study team - confirm the details with them.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Cleveland, Ohio, United States; Houston, Texas, United States. Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.