A Phase Ib Trial of Azacitidine, Venetoclax and Allogeneic NK Cells for Acute Myeloid Leukemia (ADVENT-AML)

NCT05834244 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2022-0941NCI-2023-03179
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (2)

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).

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).

Drug: Azacitidine; Drug: Venetoclax; Drug: NK Cells

Interventions

Azacitidine DRUG

Given by IV (vein)

Also known as: 5-azacytidine, 5-aza, Vidaza™, 5-AZC, AZA-CR, Ladakamycin, NSC-102816, Azacytidine

Dose Escalation; Dose Expansion

Venetoclax DRUG

Given by PO

Also known as: ABT-199, GDC-0199

Dose Escalation; Dose Expansion

NK Cells DRUG

Given by IV (vein)

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify 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 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 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

You may not qualify 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 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.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (2)

Case Western Reserve University

Cleveland, Ohio, 44106, United States

RECRUITING

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Abhishek Maiti, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abhishek Maiti, MD

CONTACT

713-792-7305; amaiti@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2023
• First Posted: April 28, 2023
• Study Start: October 26, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2028
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

US (2)