Comparing venetoclax and azacitidine to intensive chemotherapy for newly diagnosed AML patients with NPM1 mutation
Venetoclax Plus Azacitidine Versus Standard Intensive Chemotherapy for Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) and NPM1 Mutations Eligible for Intensive Treatment
This study is testing if a gentler combination of venetoclax and azacitidine can help newly diagnosed AML patients with an NPM1 mutation feel better and avoid the harsh side effects of standard chemotherapy.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 146 (estimated) |
| Ages | 18 Years to 70 Years |
| Sex | All |
| Sponsor | Technische Universität Dresden Academic / other |
| Drugs / interventions | gemtuzumab, chemotherapy, doxorubicin |
| Locations | 18 sites (Essen, North Rhine-Westphalia and 17 other locations) |
| Trial ID | NCT05904106 on ClinicalTrials.gov |
What this trial studies
This phase II clinical trial evaluates the effectiveness and safety of a non-intensive treatment regimen combining venetoclax and azacitidine against the standard intensive chemotherapy plus gemtuzumab ozogamicin in patients with newly diagnosed acute myeloid leukemia (AML) who have an NPM1 mutation. The study aims to address the high toxicity associated with traditional chemotherapy, which often leads to severe side effects and prolonged hospital stays. By focusing on a less toxic treatment approach, the trial seeks to improve patient outcomes and reduce the burden of treatment-related complications.
Who should consider this trial
Good fit: Ideal candidates for this study are adults aged 18-70 with newly diagnosed CD33-positive AML and an NPM1 mutation who are fit for intensive chemotherapy.
Not a fit: Patients who are not newly diagnosed or do not have the NPM1 mutation may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could offer a safer and more effective option for patients with NPM1 mutated AML, potentially leading to better quality of life and outcomes.
How similar studies have performed: Other studies have shown promise in using targeted therapies like venetoclax in AML, suggesting that this approach may be beneficial, although this specific combination is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. A signed informed consent
2. Newly diagnosed CD33-positive AML with NPM1 mutation according to WHO criteria
3. Age 18-70 years
4. Fit for intensive chemotherapy, defined by
* ECOG performance status of 0-2
* Adequate hepatic function: ALAT/ASAT/Bilirubin ≤ 2.5 x ULN unless considered due to leukemic organ involvement Note: Subjects with Gilbert's Syndrome may have a bilirubin \> 2.5 × ULN per discussion between the investigator and Coordinating investigator.
* Adequate renal function assessed by serum creatinine ≤ 1.5x ULN OR creatinine clearance (by Cockcroft Gault formula) ≥ 50 mL/min
5. WBC \< 25 x 109/L (\<25,000/µL), prior hydroxyurea is permitted to meet this criterion
6. Ability to understand and the willingness to sign a written informed consent.
7. Male subjects must agree to refrain from unprotected sex and sperm donation from time point of signing the informed consent until 7 months after the last dose of study drug.
8. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 72 hours before first dose of study drug.
Exclusion Criteria:
1. Activating FLT3 mutation
2. Relapsed or refractory AML
3. AML after antecedent myelodysplasia (MDS) with prior cytotoxic treatment
4. Prior history of malignancy, other than MDS, unless the subject has been free of the disease for ≥ 1 year prior to start of study treatment (exceptions are basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or of the breast, incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis clinical staging system))
5. Previous treatment with HMA or venetoclax
6. Previous treatment for AML except hydroxyurea
7. Cumulative previous exposure to anthracyclines of \> 200 mg/m\^2 doxorubicin equivalents
8. CNS involvement or extramedullary disease only
9. Known hypersensitivity to excipients of the preparation or any agent given in association with this study including venetoclax, azacitidine, cytarabine, daunorubicin, gemtuzumab-ozogamicin, or mitoxantrone
10. Known positivity for human immunodeficiency virus (HIV) and History of active or chronic infectious hepatitis unless serology demonstrates clearance of infection (i.e.
PCR undetectable viral load for hepatitis).
11. Inability to swallow oral medications
12. Any malabsorption condition
13. Cardiovascular disability status of New York Heart Association (NYHA) Class ≥ 2; unstable coronary artery disease (MI more than 6 months prior to study entry is permitted); serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
Note: Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
14. Chronic respiratory disease that requires continuous oxygen use
15. Substance abuse, medical, psychological, or social conditions that may interfere with the subject's cooperation with the requirements of the trial or evaluation of the study results
16. Simultaneous participation in another interventional clinical trial
17. Pregnant or breastfeeding women. Breastfeeding has to be discontinued before onset of and during treatment and should be discontinued for at least 3 months after end of treatment.
18. Patients who are unwilling to follow strictly highly effective contraception requirements including hormonal contraceptives with an Pearl Index \< 1% per year in combination with a barrier method from time point of signing the informed consent until 7 months after the last dose of study drug unless one of the following criteria is met:
* post-menopausal (12 months natural amenorrhea or 6 months amenorrhea with serum FSH \> 40 U/ml)
* postoperative (6 weeks after bilateral ovarectomy with or without hysterectomy)
* medically confirmed ovarian failure
* vasectomy Note: At present, it is not known whether the effectiveness of hormonal contraceptives is reduced by venetoclax. For this reason, women must use a barrier method in addition to hormonal contraceptive methods.
19. History of clinically significant liver cirrhosis (e.g., Child-Pugh class B and C)
20. Live-virus vaccines given within 28 days prior to the initiation of study treatment Note: corona vaccines are not live-virus vaccines and are excluded from this criterion.
Where this trial is running
Essen, North Rhine-Westphalia and 17 other locations
- Universitätsklinikum Essen — Essen, North Rhine-Westphalia, Germany (Recruiting)
- Universitätsklinikum Aachen — Aachen, Germany (Recruiting)
- Universitätsklinikum Augsburg — Augsburg, Germany (Recruiting)
- Klinikum Chemnitz gGmbH — Chemnitz, Germany (Recruiting)
- Universiätsklinikum Köln — Cologne, Germany (Not_yet_recruiting)
- Universitätsklinikum Dresden — Dresden, Germany (Recruiting)
- Universitätsklinikum Erlangen — Erlangen, Germany (Recruiting)
- Johann Wolfgang Goethe-Universität — Frankfurt am Main, Germany (Recruiting)
- Universitätsklinikum Halle — Halle, Germany (Recruiting)
- Universitätsklinikum Heidelberg — Heidelberg, Germany (Recruiting)
- Universitätsklinikum Schleswig-Holstein — Kiel, Germany (Recruiting)
- Universitätsklinikum Leipzig — Leipzig, Germany (Recruiting)
- Klinikum Mannheim gGmbH — Mannheim, Germany (Recruiting)
- Philipps-Universität Marburg Fachbereich Medizin — Marburg, Germany (Recruiting)
- Universitätsklinikum Münster — Münster, Germany (Recruiting)
- Klinikum Nürnberg-Nord — Nuremberg, Germany (Recruiting)
- Krankenhaus Barmherzige Brüder — Regensburg, Germany (Recruiting)
- Robert-Bosch-Krankenhaus — Stuttgart, Germany (Recruiting)
Study contacts
- Principal investigator: Christoph Röllig, Prof. — Technische Universität Dresden, Medical Faculty Carl Gustav Carus
- Study coordinator: Manja Reimann, Dr.
- Email: vincent@ukdd.de
- Phone: +49 351 458
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.