Venetoclax With Combination Chemotherapy in Treating Patients With Newly Diagnosed or Relapsed or Refractory Acute Myeloid Leukemia

NCT03214562 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2016-0979NCI-2018-01119
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/II trial studies the best dose and side effects of venetoclax and how well it works when given with combination chemotherapy in treating patients with newly diagnosed acute myeloid leukemia or acute myeloid leukemia that has come back or does not respond to treatment. Venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine, cytarabine, filgrastim and idarubicin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax together with combination chemotherapy may work better in treating patients with acute myeloid leukemia.

Conditions

High Risk Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (10)

• Overall response rate (ORR)

  Defined as complete response (CR) + CR with incomplete blood count recovery (CRi) + partial response (PR). Will be estimated along with the 95% credible interval.

  Up to 6 years

• CR/CRi rate

  Will be estimated along with the 95% credible interval.

  Up to 6 years

• Hematologic response

  Will be estimated along with the 95% credible interval.

  Up to 6 years

• Duration of response

  Defined as the number of days from the date of initial response (PR or better) to the date of first documented disease progression/relapse or death, whichever occurs first. Will be calculated for all patients.

  From the date of initial response, assessed up to 6 years

• Event-free survival

  Defined as the number of days from the date of treatment initiation (i.e., course 1 day 1) to the date of documented treatment failure, relapses from CR, or death from any cause, whichever occurs first. Will be calculated for all patients. Estimated using Kaplan-Meier method. Log-rank tests will be used to compare among subgroups of patients.

  From the date of treatment initiation, assessed up to 6 years

• Overall survival

  Estimated using Kaplan-Meier method. Log-rank tests will be used to compare among subgroups of patients.

  Up to 6 years

• Anti-tumor activity

  Will be summarized graphically and with descriptive statistics.

  Up to 6 years

• Pharmacodynamic markers

  Two samples t-test /Wilcoxon rank sum tests will be used to compare pharmacodynamics/pharmacokinetics (PD/PK) parameters between responder and non-responders, and logistic regression analysis will also be used to evaluate the association of PD/PK parameters with response.

  Up to 6 years

• Drug exposure levels

  Will be summarized graphically and with descriptive statistics.

  Up to 6 years

• Overall incidence and severity of all adverse events

  Graded using Common Toxicity Criteria version 4.0. Safety data will be summarized using frequency and percentage, by category and severity.

  Up to 6 years

Secondary Outcomes (1)

• Morphologic leukemia-free state

  Up to 6 years

Other Outcomes (1)

• Exploratory biomarkers

  Up to 6 years

Study Arms (1)

Treatment (venetoclax, FLAG-IDA)

EXPERIMENTAL

See detailed description.

Drug: Cytarabine; Biological: Filgrastim; Drug: Fludarabine; Drug: Idarubicin; Biological: Pegfilgrastim; Drug: Venetoclax

Interventions

Cytarabine DRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (venetoclax, FLAG-IDA)

Filgrastim BIOLOGICAL

Given SC

Also known as: G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim

Treatment (venetoclax, FLAG-IDA)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (venetoclax, FLAG-IDA)

Idarubicin DRUG

Given IV

Also known as: 4-Demethoxydaunomycin, 4-Demethoxydaunorubicin, 4-DMDR

Treatment (venetoclax, FLAG-IDA)

Pegfilgrastim BIOLOGICAL

Given SC

Also known as: Filgrastim SD-01, filgrastim-SD/01, Fulphila, HSP-130, Jinyouli, Neulasta, Neulastim, Pegfilgrastim Biosimilar HSP-130, Pegfilgrastim Biosimilar Pegcyte, Pegfilgrastim-jmdb, SD-01, SD-01 sustained duration G-CSF

Treatment (venetoclax, FLAG-IDA)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (venetoclax, FLAG-IDA)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of AML by World Health Organization (WHO) criteria. Patients with high risk myelodysplastic syndrome (MDS) as defined by the presence of \>= 10% blasts are also eligible at the discretion of the principal investigator
• Patients older than 65 who are deemed fit to receive intensive chemotherapy by the treating physician will be eligible after discussion with the principal investigator (PI).
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Creatinine clearance \>= 30 mL/min based on the Cockcroft-Gault equation
• Total bilirubin \< 1.5 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \< 3 x ULN unless considered due to leukemic involvement
• Ability to understand and provide signed informed consent
• 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
• Only patients who are relapsed, refractory, or intolerant of standard AML therapy will be eligible for Part 1 (minimum of 1 prior line of AML-directed therapy)

You may not qualify if:

• Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British \[FAB\] class M3-AML)
• Patients having received any prior BCL2 inhibitor therapy
• Subject has known active central nervous system (CNS) involvement with AML
• Patients with New York Heart Association (NYHA) class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) \< 40% by echocardiogram or multi-gated acquisition (MUGA) scan
• Patients with a history of myocardial infarction within the last 6 months or unstable / uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias
• Patients with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C
• Patients with known dysphagia, short-gut syndrome, or other conditions that would affect the ingestion or gastrointestinal absorption of drugs administered orally
• Subject has any other significant medical or psychiatric history that in the opinion of the investigator would adversely affect participation in this study
• Subject has a white blood cell count \> 25 x 10{9}/L. (Note: hydroxyurea is permitted to meet this criterion)
• Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception (a) appropriate method(s) of contraception include oral or injectable hormonal birth control, intrauterine device (IUD), and double barrier methods (for example a condom in combination with a spermicide)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

• DiNardo CD, Jen WY, Takahashi K, Kadia TM, Loghavi S, Daver NG, Xiao L, Reville PK, Issa GC, Short NJ, Sasaki K, Wang SA, Mullin JK, Pierce S, Bradley C, Borthakur G, Maiti A, Alvarado Y, Pemmaraju N, Ferrajoli A, Swaminathan M, Ohanian M, Abbas HA, Hammond D, Burger J, Haddad F, Montalban-Bravo G, Chien K, Masarova L, Yilmaz M, Jain N, Andreeff M, Garcia-Manero G, Kornblau S, Ravandi F, Jabbour E, Konopleva MY, Kantarjian HM. Long term results of venetoclax combined with FLAG-IDA induction and consolidation for newly diagnosed and relapsed or refractory acute myeloid leukemia. Leukemia. 2025 Apr;39(4):854-863. doi: 10.1038/s41375-025-02531-8. Epub 2025 Feb 25.

  PMID: 40000842 DERIVED

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine; Filgrastim; Granulocyte Colony-Stimulating Factor; fludarabine; Idarubicin; pegfilgrastim; venetoclax

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides

Study Officials

• Courtney DiNardo

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

DiNardo, MD

CONTACT

(713) 794-1141; cdinardo@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: July 10, 2017
• First Posted: July 11, 2017
• Study Start: September 26, 2017
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (1)