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Acute Myeloid LeukemiaPhase 1NCT03709758

Venetoclax in Combination With Intensive Induction and Consolidation Chemotherapy in Treatment Naïve AML

A Phase 1 study testing Venetoclax, Daunorubicin and Cytarabine in people with Acute Myeloid Leukemia, run by Dana-Farber Cancer Institute at 2 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This research study is studying the combination of venetoclax and chemotherapy as a possible treatment for acute myelogenous leukemia (AML). The drugs involved in this study are: Venetoclax Daunorubicin Cytarabine Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Venetoclax, Daunorubicin and Cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
2 sitesUnited States
Study dates
17 Oct 2018to 1 Dec 2026
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 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Patients with AML who are newly diagnosed according to the WHO 2016 Classification and previously untreated with the exception of hydroxyurea. ATRA pretreatment for suspected APL for less than 5 days is allowed. Eligible patients with AML arising from an antecedent hematologic disease (AHD) including MDS, may have been treated for their prior hematologic disease (except for allogenic transplant).
  • AML patients include de-novo AML, AML evolving from MDS or other AHD and AML after previous cytotoxic therapy or radiation (secondary AML).
  • For a diagnosis of AML, a bone marrow or peripheral blast count of 20% or more is required.
  • In AML with monocytic or myelomonocytic differentiation, monoblasts and promonocytes, but not abnormal mature monocytes, are counted as blast equivalents.
  • Patients must be ≥18 and ≤60 years old.
  • Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2. (See protocol Appendix D.)
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  • LVEF ≥ 45% by MUGA or ECHO at screening.
  • Adequate renal function as demonstrated by a calculated creatinine clearance ≥ 50 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula.
  • Adequate liver function as demonstrated by:
  • aspartate aminotransferase (AST) ≤ 2.5 × ULN*
  • alanine aminotransferase (ALT) ≤ 2.5× ULN*
  • total bilirubin ≤ 1.5 × ULN*
  • Unless considered due to leukemic organ involvement.
  • Subjects with Gilbert's Syndrome may have a total bilirubin > 1.5 × ULN per discussion with the overall study PI
  • Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug.
  • Females of childbearing potential (i.e., not postmenopausal for at least 1 year or not surgically sterile) must have negative results by a serum pregnancy test performed within 7 days of day 1.
  • Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Who cannot join

  • Subject has acute promyelocytic leukemia, inversion16, t(8;21) or FLT3 mutant AML as described below. Contact PI with questions.
  • Inversion 16 and t(8;21): CBF chromosomal abnormalities may be assessed by molecular (PCR), metaphase cytogenetics, or FISH
  • FLT3: ITD or a point mutation in the TKD loop of variant allele fractions ≥5% by PCR, capillary electrophoresis, or NGS panel capable of defining FLT3 allelic burden
  • Subject has known active CNS involvement with AML.
  • Subject has tested positive for HIV (due to potential drug-drug interactions between antiretroviral medications and venetoclax, as well as anticipated venetoclax mechanism-based lymphopenia that may potentially increase the risk of opportunistic infections). Note: HIV testing is not required.
  • Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months. (Hepatitis B or C testing is not required). Subjects with serologic evidence of prior vaccination to HBV [i.e., HBs Ag-, and anti-HBs+] are allowed.
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  • Subject has received the following within 7 days prior to the initiation of study treatment:
  • Strong or moderate CYP3A inducers (see Appendix C)
  • Strong and moderate CYP3A inhibitors (see Appendix C)
  • Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment.
  • Subject has a cardiovascular disability status of New York Heart Association Class ≥ 2. 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.
  • Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study.
  • Subject has chronic respiratory disease that requires continuous oxygen use.
  • Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.
  • Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to: uncontrolled systemic infection.
  • Subject has a history of other malignancies prior to study entry, with the exception of:
  • Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
  • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
  • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
  • Prior malignancies treated with (surgery+/- chemotherapy+/- radiation) that have remained disease free for at least two years after completion of therapy
  • Subject has a white blood cell count > 25 × 109/L. Note: Hydroxyurea is permitted to meet this criterion.
  • Subject treated with any form of chemotherapy, immunotherapy, or investigative agent within 1 month of enrollment.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Chicago

    Chicago, Illinois, 60637

Other trials in United States

About this study

Official title: Phase 1b Study of Venetoclax in Combination With Intensive Induction and Consolidation Chemotherapy in Treatment Naïve Subjects With Acute Myelogenous Leukemia

This research study is studying the combination of venetoclax and chemotherapy as a possible treatment for acute myelogenous leukemia (AML).

The drugs involved in this study are:

  • Venetoclax
  • Daunorubicin
  • Cytarabine
Read the detailed description

This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved venetoclax for this specific disease but it has been approved for other uses.

In this research study, the investigators are combining the use of venetoclax (the investigational drug being studied) with chemotherapy drugs daunorubicin and cytarabine. The investigators are looking to determine the highest dose of venetoclax that can be given safely in combination with these chemotherapy drugs.

Depending on when the participant join the study, the participant may participate in part 1 (induction with venetoclax escalation), part 2 (consolidation with venetoclax escalation), or part 3 (an expansion cohort utilizing the maximum tolerated doses identified in parts 1 and 2). The study doctor will tell the participant which part of the study they will join.

Being tested
Venetoclax, Daunorubicin, Cytarabine
Keywords
Acute Myeloid Leukemia
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.

  • VenetoclaxDrug

    Also called Venclexta

    Venetoclax blocks an important pathway that promotes cell survival in tumor cells that overexpress BCL-2, so venetoclax causes cells to die

  • DaunorubicinDrug

    Also called Cerubidine

    Chemotherapy is most effective at killing cells that are rapidly dividing.

  • CytarabineDrug

    Also called Cytosar-U

    Chemotherapy is most effective at killing cells that are rapidly dividing.

Study groups in NCT03709758
Study groupRoleWhat they receive
Venetoclax+Daunorubicin+CytarabineExperimental* Venetoclax administered orally on days 1 to 11 daily * Daunorubicin administered intravenously on days 2-4 * Cytarabine administered on days 2-8 by continuous IV infusion
Receives: Drug: Venetoclax; Drug: Daunorubicin; Drug: Cytarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (Induction)

    To determine a safe and tolerable dose of venetoclax that can be given in combination with standard induction therapy to patients with newly diagnosed AML.

    Measured: 2 years

  2. Maximum Tolerated Dose (Consolidation)

    To determine a safe and tolerable dose of venetoclax and that can be given with a cycle of high dose cytarabine in consolidation after achievement of remission with induction therapy at the established MTD of venetoclax.

    Measured: 2 years

Secondary outcomes (4)

  1. Complete Response Rate

    1. To obtain preliminary data as to the efficacy (Complete Remission (CR), Complete remission with incomplete platelet recovery (CRp), Complete remission with incomplete hematologic recovery (CRi), and minimal residual disease (MRD) negative CR) of combining venetoclax with standard induction and consolidation chemotherapy for AML.

    Measured: 2 years

  2. Exploratory analysis concerning the impact of BH3 profiling on response when venetoclax is combined with standard induction and consolidation chemotherapy in AML.

    BH3 profiling will be performed at the time of screening, and on PB blasts just prior to start of IV chemotherapy on day 2 of induction. These studies will determine if BH3 profile changes are induced by venetoclax exposure. Exploratory research analyses may not be included in the clinical study report.

    Measured: 2 years

  3. Determine the pharmacodynamic effects of combo venetoclax with standard chemotherapy in AML on apoptosis and other intracellular events in AML blasts exposed in patients to a combination of venetoclax plus standard induction chemo.

    A change in leukocytosis or blast counts will be evaluated as a measure of venetoclax-induced pharmacodynamic activity.

    Measured: 2 years

  4. Exploratory analysis concerning the impact of pre-therapy disease factors including mutational profile on outcome in AML patients who receive venetoclax in combination with standard chemotherapy.

    Single cell mass cytometry (CyTOF) will be used to observe changes in the levels of BCL-2 and associated proteins before therapy, at time of response assessment, upon recovery from consolidation (if applicable) and at relapse if feasible. Exploratory research analyses may not be included in the clinical study report.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Oct 2018
  2. Study start17 Oct 2018
  3. Primary completion23 Feb 2025
  4. Study completion1 Dec 2026 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03709758
Sponsor's protocol ID
18-351
Status last verified
Oct 2026
First submitted
12 Oct 2018
Last updated
22 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Venetoclax, Daunorubicin and Cytarabine in people with Acute Myeloid Leukemia, run by Dana-Farber Cancer Institute 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 17 inclusion and 22 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: under way, not looking for participants, as of the sponsor's last update on 22 Oct 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (Induction) (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03709758.

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 22 Oct 2026.

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Clinical Trial NCT03709758 | AzTrials