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Acute Myeloid Leukemia (AML)Phase 1NCT03625505

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

A Phase 1 study testing Venetoclax and Gilteritinib in people with Acute Myeloid Leukemia (AML), run by AbbVie at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia (AML)
What is being tested?
Venetoclax and Gilteritinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
11 sitesUnited States
Study dates
18 Oct 2018to 31 Aug 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Johns Hopkins University /ID# 200349

    Baltimore, Maryland, 21287

  • Northwestern Memorial Hospital /ID# 200230

    Chicago, Illinois, 60611-2927

  • Hackensack Univ Med Ctr /ID# 200229

    Hackensack, New Jersey, 07601

  • MD Anderson Cancer Center at Texas Medical Center /ID# 206686

    Houston, Texas, 77030-4000

  • David Geffen School of Medicin /ID# 200166

    Los Angeles, California, 90095

  • Norton Cancer Institute /ID# 200623

    Louisville, Kentucky, 40202-3700

  • Sylvester Comprehensive Cancer /ID# 200268

    Miami, Florida, 33136-1002

  • Weill Cornell Medical College /ID# 200109

    New York, New York, 10065

  • Hosp of the Univ of Penn /ID# 200348

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic - Rochester /ID# 200346

    Rochester, Minnesota, 55905-0001

  • UC San Francisco Medical Center-Parnassus /ID# 200205

    San Francisco, California, 94143-2202

Other trials in United States

About this study

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

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.

Being tested
Venetoclax, Gilteritinib
Keywords
Cancer, Acute Myeloid Leukemia (AML), Relapsed or Refractory AML, Pharmacokinetics, venetoclax, gilteritinib
Medical subject headings
Leukemia, Myeloid, Acute, Neoplasms, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VenetoclaxDrug

    Also called ABT-199, GDC-0199

    tablet, oral

  • GilteritinibDrug

    Also called ASP-2215

    tablet, oral

Study groups in NCT03625505
Study groupRoleWhat they receive
Dose Escalation Venetoclax + GilteritinibExperimentalDifferent combinations of dose levels for venetoclax in combination with gilteritinib will be administered to determine the recommended phase 2 dose (RPTD).
Receives: Drug: Venetoclax; Drug: Gilteritinib
Dose Expansion Venetoclax + GilteritinibExperimentalParticipants will receive venetoclax in combination with gilteritinib at the dose determined in dose escalation portion.
Receives: Drug: Venetoclax; Drug: Gilteritinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to approximately 6 months after the last participant is enrolled

  2. 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).

    Measured: Up to approximately 6 months after the last participant is enrolled

Secondary outcomes (13)

  1. Pharmacokinetics - Cmax of Venetoclax

    Maximum observed plasma concentration (Cmax) of study drug.

    Measured: Approximately 16 days after first dose of study drug

  2. Pharmacokinetics - Cmax of Gilteritinib

    Maximum observed plasma concentration (Cmax) of study drug.

    Measured: Approximately 16 days after first dose of study drug

  3. Pharmacokinetics - Tmax of Venetoclax

    Time to maximum plasma concentration (Tmax) of study drug.

    Measured: Approximately 16 days after first dose of study drug

  4. Pharmacokinetics - Tmax of Gilteritinib

    Time to maximum plasma concentration (Tmax) of study drug.

    Measured: Approximately 16 days after first dose of study drug

  5. 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.

    Measured: Approximately 16 days after first dose of study drug

  6. 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.

    Measured: Approximately 16 days after first dose of study drug

  7. 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.

    Measured: Approximately 16 days after first dose of study drug

  8. 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.

    Measured: Approximately 16 days after first dose of study drug

  9. 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).

    Measured: Up to approximately 6 months after the last participant is enrolled

  10. 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.

    Measured: Up to approximately 6 months after the last participant is enrolled

  11. 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).

    Measured: Up to approximately 6 months after the last participant is enrolled

  12. 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.

    Measured: Up to approximately 6 months after the last participant is enrolled

  13. 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.

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2018
  2. Study start18 Oct 2018
  3. Primary completion31 Aug 2021
  4. Study completion31 Aug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03625505
Sponsor's protocol ID
M16-802
Status last verified
Sep 2021
First submitted
8 Aug 2018
Last updated
14 Sep 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Publications

  • Kennedy VE, Peretz CAC, Walia A, Chyla B, Sun Y, Hill JE, Tran E, Koh AD, Ferng TT, Pintar S, Jones M, Popescu B, Lomeli I, Chehab F, Murad N, John A, Roy RP, Olshen AB, Berryhill CA, Davis C, Angus SP, Rivera JM, Meshulam A, Stieglitz E, Joshi SK, Traer E, Dail M, Hamidi H, Altman JK, Daver NG, Levis MJ, McCloskey J, Perl AE, Smith CC. Dynamic genetic and nongenetic RAS pathway activation drives resistance to FLT3 and BCL2 inhibitor therapy. Blood. 2026 Jun 1:blood.2025032466. doi: 10.1182/blood.2025032466. Online ahead of print.

    PubMed 42224378

  • 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.

    PubMed 35849791

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Venetoclax and Gilteritinib in people with Acute Myeloid Leukemia (AML), run by AbbVie at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended Phase 2 Dose (RPTD) of Co-administered Study Drugs (time frame: Up to approximately 6 months after the last participant is enrolled). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03625505, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2021.

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Clinical Trial NCT03625505 | AzTrials