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Venetoclax with intensive induction and consolidation chemotherapy for newly diagnosed AML and MDS‑EB‑2

A Randomized, Placebo-Controlled Phase III Study of Induction and Consolidation Chemotherapy With Venetoclax in Adult Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome With Excess Blasts-2

PHASE3 · University of Ulm · NCT04628026

This trial tests whether adding venetoclax to standard intensive induction and consolidation chemotherapy helps adults (18–75) with newly diagnosed acute myeloid leukemia or MDS‑EB‑2.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment650 (estimated)
Ages18 Years to 75 Years
SexAll
SponsorUniversity of Ulm (other)
Drugs / interventionschemotherapy
Locations91 sites (Innsbruck and 90 other locations)
Trial IDNCT04628026 on ClinicalTrials.gov

What this trial studies

This is a prospective, multicenter, double-blind, randomized, placebo-controlled Phase 3 trial with an initial feasibility run‑in dose‑escalation phase to establish the venetoclax dose. After the run‑in, eligible patients are randomized to receive intensive induction chemotherapy with either venetoclax or placebo, followed by consolidation according to the initial assignment and cooperative‑group or investigator regimens. Patients who achieve CR, CRi, or MLFS after induction may proceed to consolidation, and decisions about allogeneic or autologous hematopoietic cell transplantation are made per institutional standards and patient risk profiles. Molecular analyses are performed centrally to inform classification and eligibility.

Who should consider this trial

Good fit: Adults aged 18–75 with newly diagnosed AML or MDS‑EB‑2 who are eligible for intensive chemotherapy, have ECOG performance status ≤2, and adequate kidney and liver function are the intended participants.

Not a fit: Patients older than 75, those not eligible for intensive chemotherapy, or those with significant organ dysfunction or comorbidities are unlikely to benefit from this intensive combination approach.

Why it matters

Potential benefit: If successful, adding venetoclax could increase remission rates and improve longer‑term outcomes compared with chemotherapy alone.

How similar studies have performed: Venetoclax has improved response rates in combination with lower‑intensity therapies for older/unfit AML, and early‑phase studies combining venetoclax with intensive chemotherapy have shown promising remission signals, but phase 3 confirmation is limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Patients with newly diagnosed acute myeloid leukemia (AML) according to the International Consensus Classification (ICC).
2. Age ≥ 18 and ≤ 75 years.
3. Patients considered eligible for intensive chemotherapy.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
5. Molecular analysis centrally performed in AMLSG and HOVON laboratories.
6. Adequate renal function as evidenced by serum creatinine ≤ 2.0 × upper limit of norm (ULN) or creatinine clearance \>40 mL/min based on the Cockcroft-Gault glomerular filtration rate (GFR).
7. Adequate hepatic function as evidenced by:

   * Serum total bilirubin ≤ 2.5 × ULN unless considered due to Gilbert's disease, or leukemic involvement following approval by the Principal Investigators or Trial Coordinators of the study
   * Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 3.0 × ULN, unless considered due to leukemic involvement following approval by the Principal Investigators or Trial Coordinators.
8. No prior chemotherapy for AML, except hydroxyurea for up to 14 days during the diagnostic screening phase for the control of peripheral leukemic blasts in patients with leukocytosis (e.g., white blood cell \[WBC\] counts \> 25x109/L); patients may have had previous treatment with erythroid stimulating agents (ESA) or hypomethylating agents (HMAs) for an antecedent phase of MDS; ESA and HMAs have to be stopped at least four weeks before start of study treatment.
9. Patients must not have received a known strong or moderate CYP3A inducer 7 days before start of study treatment. Patients must have no known medical conditions requiring chronic therapy with moderate or strong CYP3A inducers.
10. Female patient must either:

    * Be of nonchildbearing potential:

      * Postmenopausal (defined as at least 1 year without any menses)
      * Documented surgically sterile (e.g. documented hysterectomy, bilateral oophorectomy, bilateral salpingectomy or congenital sterile) or status post hysterectomy (at least 1 month prior to screening)
    * Or, if of childbearing potential (not surgically sterile and not postmenopausal)

      * Not planning to become pregnant during the study and for 6 months after the final study drug administration
      * And have a negative urine or serum pregnancy test at screening
      * And, if heterosexually active, agree to consistently apply one highly effective\* method of birth control in combination to a barrier method for the duration of the study and for 27 weeks after the final study drug administration

        \*Highly effective forms of birth control include
      * Consistent and correct usage of established hormonal contraceptives that inhibit ovulation for at least 1 month prior to taking study drug. (hormonal contraception is only a highly effective method of birth control, if a combined \[estrogen and progestogen containing\] hormonal contraception or a progestogen-only hormonal contraception - both associated with inhibition of ovulation - is used.
      * Established intrauterine device (IUD) or intrauterine system (IUS)
      * Bilateral tubal occlusion
      * Vasectomy - a vasectomy is highly effective contraception method provided the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used.
      * Male is sterile due to a bilateral orchiectomy.
      * Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual activity during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient.

        \*List is not all inclusive. Prior to enrolment, the investigator is responsible for confirming patient will utilize highly effective forms of birth control in combination with a barrier method according to locally accepted standards during the protocol defined period.
      * Female patient must agree not to breastfeed starting at screening and throughout the study period, and for 2 months and 1 week after the final study drug administration.
      * Female patient must not donate ova starting at screening and throughout the study period, and for 27 weeks after the final study drug administration.
11. Men must use a latex condom during any sexual contact with WOCBP, even if they have undergone a successful vasectomy and must agree to avoid to father a child (while on therapy and for 27 weeks after the final study drug administration). In addition, their female partners of childbearing potential have to use a highly effective method of birth control.
12. Male patient must not donate sperm starting at screening and throughout the study period and for 27 weeks after the final study drug administration.
13. Able to understand and willing to sign an informed consent form (ICF).

Where this trial is running

Innsbruck and 90 other locations

+41 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Acute Myeloid Leukemia, adult patients

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.