A Study to Assess Safety and Efficacy of Venetoclax in Combination With Gilteritinib in Participants With Relapsed/Refractory Acute Myeloid Leukemia

Conditions

Acute Myeloid Leukemia (AML)

Keywords

Cancer, Acute Myeloid Leukemia (AML), Relapsed or Refractory AML, Pharmacokinetics, venetoclax, gilteritinib

Brief summary

A dose-escalation study evaluating the safety, tolerability, pharmacokinetics (PK) and efficacy of venetoclax, in combination with gilteritinib, in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) who have failed to respond to, and/or have relapsed or progressed after at least 1 prior therapy.

Vanessa E Kennedy, Cheryl A. C. Peretz, Anushka Walia, Brenda Chyla, Yan Sun et al. (34 authors)

Blood2026-06-01

10.1182/blood.2025032466

Multi-Omic Single-Cell Sequencing Reveals Genetic and Immunophenotypic Clonal Selection in Patients With FLT3-Mutated AML Treated With Gilteritinib/Venetoclax

Vanessa E. Kennedy, Cheryl A.C. Peretz, Paul P. Lee, Brenda Chyla, Yan Sun et al. (15 authors)

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10.1182/blood-2022-160304

Venetoclax Plus Gilteritinib for FLT3-Mutated Relapsed/Refractory Acute Myeloid Leukemia

Naval Daver, Alexander E. Perl, Joseph Maly, Mark J. Levis, Ellen K. Ritchie et al. (19 authors)

Journal of Clinical Oncology2022-07-18178 citations

10.1200/jco.22.00602

Venetoclax in Combination with Gilteritinib Demonstrates Molecular Clearance of FLT3 mutation in Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia

Naval Daver, Alexander E. Perl, Joseph Maly, Mark J. Levis, Ellen K. Ritchie et al. (18 authors)

Blood2021-11-0511 citations

10.1182/blood-2021-150743

Efficacy and Safety of Venetoclax in Combination with Gilteritinib for Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia in the Expansion Cohort of a Phase 1b Study

Naval Daver, Jessica K. Altman, Joseph Maly, Mark J. Levis, Ellen K. Ritchie et al. (16 authors)

Blood2020-11-0427 citations

10.1182/blood-2020-139705

Venetoclax in Combination with Gilteritinib in Patients with Relapsed/Refractory Acute Myeloid Leukemia: A Phase 1b Study

Alexander E. Perl, Naval Daver, Keith W. Pratz, Joseph Maly, Wan‐Jen Hong et al. (9 authors)

Blood2019-11-1341 citations

10.1182/blood-2019-127416

Interventions

DRUGVenetoclax

tablet, oral

DRUGGilteritinib

tablet, oral

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Should have an established, confirmed diagnosis of Acute Myeloid Leukemia (AML) by World Health Organization (2016). * Should have failed at least 1 line of prior therapy (defined as failure to respond to therapy, and/or progression during or after therapy). * Should have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. * Should have adequate hematologic, kidney and liver function as described in the protocol. * For participants enrolling into the Expansion Cohort only: a documented FMS-like Tyrosine Kinase (FLT3) mutation in bone marrow or peripheral blood, as described in the protocol.

Exclusion criteria

* Has a diagnosis of acute promyelocytic leukemia (APL) or BCR-ABL-positive leukemia. * Has a history of other malignancies within 2 years prior to study entry, with exceptions as described in the protocol. * Has active central nervous system leukemia. * Has a history of chronic New York Heart Association (NYHA) class IV heart failure. * Has a corrected QT interval of \> 450 ms. * Has a chronic respiratory disease that requires continuous oxygen use.

Design outcomes

Primary

Measure	Time frame	Description
Recommended Phase 2 Dose (RPTD) of Co-administered Study Drugs	Up to approximately 6 months after the last participant is enrolled	The RPTD of co-administered venetoclax and gilteritinib will be determined during the dose escalation phase of the study. RPTD will be determined using available safety and pharmacokinetics data.
Modified Composite Complete Remission (CRc)	Up to approximately 6 months after the last participant is enrolled	Modified CRc rate is defined as the proportion of participants with documented complete response (CR) + CR with partial blood count recovery (CRp) + CR with incomplete blood count recovery (CRi) plus Morphologic Leukemia-Free State (MLFS) based on guidelines adapted from the International Working Group (IWG) for Acute Myeloid Leukemia (AML).

Secondary

Measure	Time frame	Description
Pharmacokinetics - Tmax of Venetoclax	Approximately 16 days after first dose of study drug	Time to maximum plasma concentration (Tmax) of study drug.
Pharmacokinetics - Tmax of Gilteritinib	Approximately 16 days after first dose of study drug	Time to maximum plasma concentration (Tmax) of study drug.
Pharmacokinetics - AUCt of Venetoclax	Approximately 16 days after first dose of study drug	Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt) of study drug.
Pharmacokinetics - AUCt of Gilteritinib	Approximately 16 days after first dose of study drug	Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt) of study drug.
Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Venetoclax	Approximately 16 days after first dose of study drug	Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of study drug.
Pharmacokinetics - Cmax of Venetoclax	Approximately 16 days after first dose of study drug	Maximum observed plasma concentration (Cmax) of study drug.
Composite Complete Remission (CRc) Rate	Up to approximately 6 months after the last participant is enrolled	CRc is defined as the proportion of participants with documented CR + CRp + CRi based on guidelines adapted from the International Working Group (IWG) for Acute Myeloid Leukemia (AML).
Duration of Response (DOR) of Modified Composite Complete Remission (CRc)	Up to approximately 6 months after the last participant is enrolled	DOR of modified CRc will be defined as time from the first date achieving modified CRc to disease progression (including morphologic relapse) or death from any cause whichever is earlier.
Complete Remission (CR) + with Partial Hematologic Recovery (CRh)	Up to approximately 6 months after the last participant is enrolled	It is defined as the proportion of participants achieving CR or CRh based on guidelines adapted from the International Working Group (IWG) for Acute Myeloid Leukemia (AML).
Duration of Response (DOR) of Complete Remission (CR) + Complete Remission with Partial Hematologic Recovery (CRh)	Up to approximately 6 months after the last participant is enrolled	DOR of CR + CRh will be defined as time from the first date achieving CR and/or CRh to disease progression (including morphologic relapse) or death from any cause whichever is earlier.
Number of Participants With Adverse Events	From first dose of study drug until 30 days or 5 half-lives after discontinuation of study drug administration will be collected (up to approximately 4 years)	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Gilteritinib	Approximately 16 days after first dose of study drug	Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of study drug.
Pharmacokinetics - Cmax of Gilteritinib	Approximately 16 days after first dose of study drug	Maximum observed plasma concentration (Cmax) of study drug.

Countries

United States

Outcome results

None listed