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

Primary Purpose

Acute Myeloid Leukemia (AML)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Venetoclax
Gilteritinib
Sponsored by
AbbVie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring Cancer, Acute Myeloid Leukemia (AML), Relapsed or Refractory AML, Pharmacokinetics, venetoclax, gilteritinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • David Geffen School of Medicin /ID# 200166
  • UC San Francisco Medical Center-Parnassus /ID# 200205
  • Sylvester Comprehensive Cancer /ID# 200268
  • Northwestern Memorial Hospital /ID# 200230
  • Norton Cancer Institute /ID# 200623
  • Johns Hopkins University /ID# 200349
  • Mayo Clinic - Rochester /ID# 200346
  • Hackensack Univ Med Ctr /ID# 200229
  • Weill Cornell Medical College /ID# 200109
  • Hosp of the Univ of Penn /ID# 200348
  • MD Anderson Cancer Center at Texas Medical Center /ID# 206686

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Dose Escalation Venetoclax + Gilteritinib

Dose Expansion Venetoclax + Gilteritinib

Arm Description

Different combinations of dose levels for venetoclax in combination with gilteritinib will be administered to determine the recommended phase 2 dose (RPTD).

Participants will receive venetoclax in combination with gilteritinib at the dose determined in dose escalation portion.

Outcomes

Primary Outcome Measures

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.
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).

Secondary Outcome Measures

Pharmacokinetics - Cmax of Venetoclax
Maximum observed plasma concentration (Cmax) of study drug.
Pharmacokinetics - Cmax of Gilteritinib
Maximum observed plasma concentration (Cmax) of study drug.
Pharmacokinetics - Tmax of Venetoclax
Time to maximum plasma concentration (Tmax) of study drug.
Pharmacokinetics - Tmax of Gilteritinib
Time to maximum plasma concentration (Tmax) 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.
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.
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.
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.
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).
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.
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).
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.
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.

Full Information

First Posted
August 8, 2018
Last Updated
September 7, 2021
Sponsor
AbbVie
Collaborators
Astellas Pharma Inc, Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03625505
Brief Title
A Study to Assess Safety and Efficacy of Venetoclax in Combination With Gilteritinib in Participants With Relapsed/Refractory Acute Myeloid Leukemia
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
October 18, 2018 (Actual)
Primary Completion Date
August 31, 2021 (Actual)
Study Completion Date
August 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
Collaborators
Astellas Pharma Inc, Genentech, Inc.

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML)
Keywords
Cancer, Acute Myeloid Leukemia (AML), Relapsed or Refractory AML, Pharmacokinetics, venetoclax, gilteritinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
61 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation Venetoclax + Gilteritinib
Arm Type
Experimental
Arm Description
Different combinations of dose levels for venetoclax in combination with gilteritinib will be administered to determine the recommended phase 2 dose (RPTD).
Arm Title
Dose Expansion Venetoclax + Gilteritinib
Arm Type
Experimental
Arm Description
Participants will receive venetoclax in combination with gilteritinib at the dose determined in dose escalation portion.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
ABT-199, GDC-0199
Intervention Description
tablet, oral
Intervention Type
Drug
Intervention Name(s)
Gilteritinib
Other Intervention Name(s)
ASP-2215
Intervention Description
tablet, oral
Primary Outcome Measure Information:
Title
Recommended Phase 2 Dose (RPTD) of Co-administered Study Drugs
Description
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.
Time Frame
Up to approximately 6 months after the last participant is enrolled
Title
Modified Composite Complete Remission (CRc)
Description
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).
Time Frame
Up to approximately 6 months after the last participant is enrolled
Secondary Outcome Measure Information:
Title
Pharmacokinetics - Cmax of Venetoclax
Description
Maximum observed plasma concentration (Cmax) of study drug.
Time Frame
Approximately 16 days after first dose of study drug
Title
Pharmacokinetics - Cmax of Gilteritinib
Description
Maximum observed plasma concentration (Cmax) of study drug.
Time Frame
Approximately 16 days after first dose of study drug
Title
Pharmacokinetics - Tmax of Venetoclax
Description
Time to maximum plasma concentration (Tmax) of study drug.
Time Frame
Approximately 16 days after first dose of study drug
Title
Pharmacokinetics - Tmax of Gilteritinib
Description
Time to maximum plasma concentration (Tmax) of study drug.
Time Frame
Approximately 16 days after first dose of study drug
Title
Pharmacokinetics - AUCt of Venetoclax
Description
Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt) of study drug.
Time Frame
Approximately 16 days after first dose of study drug
Title
Pharmacokinetics - AUCt of Gilteritinib
Description
Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt) of study drug.
Time Frame
Approximately 16 days after first dose of study drug
Title
Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Venetoclax
Description
Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of study drug.
Time Frame
Approximately 16 days after first dose of study drug
Title
Pharmacokinetics - AUC0-24 Post-dose of Study Drug of Gilteritinib
Description
Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of study drug.
Time Frame
Approximately 16 days after first dose of study drug
Title
Composite Complete Remission (CRc) Rate
Description
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).
Time Frame
Up to approximately 6 months after the last participant is enrolled
Title
Duration of Response (DOR) of Modified Composite Complete Remission (CRc)
Description
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.
Time Frame
Up to approximately 6 months after the last participant is enrolled
Title
Complete Remission (CR) + with Partial Hematologic Recovery (CRh)
Description
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).
Time Frame
Up to approximately 6 months after the last participant is enrolled
Title
Duration of Response (DOR) of Complete Remission (CR) + Complete Remission with Partial Hematologic Recovery (CRh)
Description
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.
Time Frame
Up to approximately 6 months after the last participant is enrolled
Title
Number of Participants With Adverse Events
Description
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.
Time Frame
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ABBVIE INC.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
David Geffen School of Medicin /ID# 200166
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UC San Francisco Medical Center-Parnassus /ID# 200205
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-2202
Country
United States
Facility Name
Sylvester Comprehensive Cancer /ID# 200268
City
Miami
State/Province
Florida
ZIP/Postal Code
33136-1002
Country
United States
Facility Name
Northwestern Memorial Hospital /ID# 200230
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-2927
Country
United States
Facility Name
Norton Cancer Institute /ID# 200623
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202-3700
Country
United States
Facility Name
Johns Hopkins University /ID# 200349
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Mayo Clinic - Rochester /ID# 200346
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905-0001
Country
United States
Facility Name
Hackensack Univ Med Ctr /ID# 200229
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Weill Cornell Medical College /ID# 200109
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Hosp of the Univ of Penn /ID# 200348
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
MD Anderson Cancer Center at Texas Medical Center /ID# 206686
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4000
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35849791
Citation
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 Dec 10;40(35):4048-4059. doi: 10.1200/JCO.22.00602. Epub 2022 Jul 18.
Results Reference
derived
Links:
URL
http://www.rxabbvie.com
Description
This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Learn more about this trial

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

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