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

A Multicenter, Open-Label Phase 1b Study to Assess Safety and Efficacy of Venetoclax in Combination With Gilteritinib in Subjects With Relapsed/Refractory Acute Myeloid Leukemia

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: Venetoclax; Drug: Gilteritinib

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicin /ID# 200166
    • San Francisco, California, United States, 94143-2202
      • UC San Francisco Medical Center-Parnassus /ID# 200205
  • Florida
    • Miami, Florida, United States, 33136-1002
      • Sylvester Comprehensive Cancer /ID# 200268
  • Illinois
    • Chicago, Illinois, United States, 60611-2927
      • Northwestern Memorial Hospital /ID# 200230
  • Kentucky
    • Louisville, Kentucky, United States, 40202-3700
      • Norton Cancer Institute /ID# 200623
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University /ID# 200349
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Mayo Clinic - Rochester /ID# 200346
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack Univ Med Ctr /ID# 200229
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College /ID# 200109
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hosp of the Univ of Penn /ID# 200348
  • Texas
    • Houston, Texas, United States, 77030-4000
      • MD Anderson Cancer Center at Texas Medical Center /ID# 206686

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Venetoclax + Gilteritinib; Different combinations of dose levels for venetoclax in combination with gilteritinib will be administered to determine the recommended phase 2 dose (RPTD).	Drug: Venetoclax; tablet, oral; Other Names: ABT-199; GDC-0199; Drug: Gilteritinib; tablet, oral; Other Names: ASP-2215
Experimental: Dose Expansion Venetoclax + Gilteritinib; Participants will receive venetoclax in combination with gilteritinib at the dose determined in dose escalation portion.	Drug: Venetoclax; tablet, oral; Other Names: ABT-199; GDC-0199; Drug: Gilteritinib; tablet, oral; Other Names: ASP-2215

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase 2 Dose (RPTD) of Co-administered Study Drugs	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.	Up to approximately 6 months after the last participant is enrolled
Modified Composite Complete Remission (CRc)	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).	Up to approximately 6 months after the last participant is enrolled

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Cmax of Venetoclax	Maximum observed plasma concentration (Cmax) of study drug.	Approximately 16 days after first dose of study drug
Pharmacokinetics - Cmax of Gilteritinib	Maximum observed plasma concentration (Cmax) of study drug.	Approximately 16 days after first dose of study drug
Pharmacokinetics - Tmax of Venetoclax	Time to maximum plasma concentration (Tmax) of study drug.	Approximately 16 days after first dose of study drug
Pharmacokinetics - Tmax of Gilteritinib	Time to maximum plasma concentration (Tmax) of study drug.	Approximately 16 days after first dose of study drug
Pharmacokinetics - AUCt of Venetoclax	Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt) of study drug.	Approximately 16 days after first dose of study drug
Pharmacokinetics - AUCt of Gilteritinib	Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt) of study drug.	Approximately 16 days after first dose of study drug
Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Venetoclax	Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of study drug.	Approximately 16 days after first dose of study drug
Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Gilteritinib	Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of study drug.	Approximately 16 days after first dose of study drug
Composite Complete Remission (CRc) Rate	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).	Up to approximately 6 months after the last participant is enrolled
Duration of Response (DOR) of Modified Composite Complete Remission (CRc)	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.	Up to approximately 6 months after the last participant is enrolled
Complete Remission (CR) + with Partial Hematologic Recovery (CRh)	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).	Up to approximately 6 months after the last participant is enrolled
Duration of Response (DOR) of Complete Remission (CR) + Complete Remission with Partial Hematologic Recovery (CRh)	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.	Up to approximately 6 months after the last participant is enrolled
Number of Participants With Adverse Events	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.	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)

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: Astellas Pharma Inc; Genentech, Inc.

Publications and helpful links

General Publications

• Daver N, Perl AE, Maly J, Levis M, Ritchie E, Litzow M, McCloskey J, Smith CC, Schiller G, Bradley T, Tiu RV, Naqvi K, Dail M, Brackman D, Siddani S, Wang J, Chyla B, Lee P, Altman JK. Venetoclax Plus Gilteritinib for FLT3-Mutated Relapsed/Refractory Acute Myeloid Leukemia. J Clin Oncol. 2022 Jul 18:JCO2200602. doi: 10.1200/JCO.22.00602. [Epub ahead of print]

Helpful Links

• This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2018
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: August 8, 2018
• First Submitted That Met QC Criteria: August 8, 2018
• First Posted (Actual): August 10, 2018

Study Record Updates

• Last Update Posted (Actual): September 14, 2021
• Last Update Submitted That Met QC Criteria: September 7, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Cancer; Pharmacokinetics; venetoclax; Acute Myeloid Leukemia (AML); gilteritinib; Relapsed or Refractory AML
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Venetoclax
• Other Study ID Numbers: M16-802

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No