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

NCT03709758 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 18-351
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief 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

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• 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.

  2 years

• 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.

  2 years

Secondary Outcomes (4)

• Complete Response Rate

  2 years

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

  2 years

• 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.

  2 years

• 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.

  2 years

Study Arms (1)

Venetoclax+Daunorubicin+Cytarabine

EXPERIMENTAL

* 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

Drug: Venetoclax; Drug: Daunorubicin; Drug: Cytarabine

Interventions

Cytarabine DRUG

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

Also known as: Cytosar-U

Venetoclax+Daunorubicin+Cytarabine

Venetoclax DRUG

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

Also known as: Venclexta

Venetoclax+Daunorubicin+Cytarabine

Daunorubicin DRUG

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

Also known as: Cerubidine

Venetoclax+Daunorubicin+Cytarabine

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.)
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Genentech, Inc.: collaborator
• Dana-Farber Cancer Institute: lead
• AbbVie: collaborator

Study Sites (2)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Daunorubicin; Cytarabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Richard Stone, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 12, 2018
• First Posted: October 17, 2018
• Study Start: October 17, 2018
• Primary Completion: February 23, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)