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Solid TumorsPhase 1/2NCT02587598

Study of INCB053914 in Subjects With Advanced Malignancies

A Phase 1/2 study testing INCB053914, I-DAC (Intermediate dose cytarabine) and Azacitidine in people with Solid Tumors, run by Incyte Corporation at 19 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is an open-label, dose-escalation study of the proviral integration site of Moloney murine leukemia virus (PIM) kinase inhibitor INCB053914 in subjects with advanced malignancies. The study will be conducted in 4 parts. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors
What is being tested?
INCB053914, I-DAC (Intermediate dose cytarabine) and Azacitidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
97 participants
Where
19 sitesUnited States
Study dates
29 Dec 2015to 11 Aug 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Aged 18 years or older
  • Confirmed diagnosis of select advanced malignancy
  • Parts 1 and 2:
  • Unresponsive to currently available therapy and there is no standard-of-care therapy available in the judgment of the investigator.
  • Not currently a candidate for curative treatment
  • Parts 3 and 4:
Show all 14Show fewer
  • Subjects with relapsed/refractory AML must have received either induction chemotherapy for AML or hypomethylating agents for hematologic disease before AML.
  • Elderly subjects (≥ 65 years) with newly diagnosed AML must be treatment naive and unfit for intensive chemotherapy.
  • Myelofibrosis subjects must have been treated with ruxolitinib for ≥ 6 months with a stable dose for ≥ 8 weeks (acceptable doses are 5 mg twice daily [BID] to 25 mg BID).
  • Willingness to undergo a pretreatment bone marrow biopsy and/or aspirate, or archival sample obtained since completion of most recent therapy (as appropriate to subjects with existing bone marrow disease or for whom bone marrow examination is a component of disease status assessment)
  • Eastern Cooperative Oncology Group (ECOG) performance status
  • Part 1: 0 or 1
  • Parts 2, 3 and 4: 0, 1, or 2
  • Life expectancy > 12 weeks or ≥ 24 weeks for Part 3 and Part 4 MF subjects.

Who cannot join

  • Inadequate bone marrow or organ function
  • Received an investigational agent within 5 half-lives or 14 days, whichever is longer, prior to receiving the first dose of study drug
  • Received non-biologic anticancer medication within 5 half-lives prior to receiving the first dose of study drug (within 6 weeks for mitomycin-C or nitrosoureas), within 28 days for any antibodies or biological therapies
  • Prior receipt of a PIM inhibitor
  • Any history of disease involving the central nervous system (Part 1). Known active disease involving the central nervous system (Part 2).
  • Screening corrected QT interval (QTc) interval > 470 milliseconds
  • Radiotherapy within the 2 weeks prior to initiation of treatment
  • Chronic or current active infection requiring systemic antibiotic, antifungal, or antiviral treatment

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites
  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Emory University-Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Texas Oncology

    Austin, Texas, 78705

  • University of Maryland

    Baltimore, Maryland, 21201

  • Dana-Farber Cancer Center

    Boston, Massachusetts, 02215

  • Oncology Hematology Care Clinical Trials LLC

    Cincinnati, Ohio, 45236

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Yale University

    New Haven, Connecticut, 06511

  • Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • University of Nebraska Medical Center

    Omaha, Nebraska, 69198

  • UC Davis comprehensive Cancer Center

    Sacramento, California, 95817

  • UCLA Medical Hematology & Oncology

    Santa Monica, California, 90095

  • Florida Cancer Specialists & Research Institute

    Sarasota, Florida, 33916

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

  • The University of Arizona Cancer Center

    Tucson, Arizona, 85719

  • Texas Oncology

    Tyler, Texas, 75702

Other trials in United States

About this study

Official title: A Phase 1/2 Study of INCB053914 in Subjects With Advanced Malignancies

This is an open-label, dose-escalation study of the proviral integration site of Moloney murine leukemia virus (PIM) kinase inhibitor INCB053914 in subjects with advanced malignancies. The study will be conducted in 4 parts. Part 1 (monotherapy dose escalation) will evaluate safety and determine the maximum tolerated dose of INCB053914 monotherapy and the recommended phase 2 dose(s) (a tolerated pharmacologically active dose that will be taken forward into the remaining parts of the study). Part 2 (monotherapy dose expansion) will further evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the recommended Phase 2 dose(s). Part 3 (combination dose finding) will evaluate safety of INCB053914 in combination with select standard of care (SOC) agents and will identify the optimal INCB053914 dose in combination with conventional SOC regimens to take forward into Part 4. Part 4 (combination dose expansion) will further evaluate the safety, efficacy and pharmacokinetics of the recommended Phase 2 dose combination(s).

Conditions
Solid Tumors
Being tested
INCB053914, I-DAC (Intermediate dose cytarabine), Azacitidine, Ruxolitinib
Keywords
leukemia, myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative neoplasms (MDS/MPN), myelofibrosis (MF), lymphoproliferative disorders, acute myeloid leukemia (AML), lymphomas, multiple myeloma (MM), PIM kinases
Medical subject headings
Leukemia, Myelodysplastic Syndromes, Myeloproliferative Disorders, Primary Myelofibrosis, Lymphoproliferative Disorders, Leukemia, Myeloid, Acute, Lymphoma, Multiple Myeloma

What participants receive

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

  • INCB053914Drug

    Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria.

    INCB053914 tablets to be administered by mouth.

  • I-DAC (Intermediate dose cytarabine)Drug

    Cytarabine dose will be 1 g/m^2. Cytarabine will be administered as an intravenous (IV) infusion.

  • AzacitidineDrug

    Also called Vidaza®

    Azacitidine dose will be 75 mg/m^2. Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).

  • RuxolitinibDrug

    Starting dose of ruxolitinib will be the dose the subject was on at study entry Ruxolitinib will be administered by mouth.

Study groups in NCT02587598
Study groupRoleWhat they receive
Parts 1 and 2: INCB053914 100 mg QDExperimentalINCB053914 will be self-administered orally once a day in as a 100mg immediate release tablet as a monotherapy.
Receives: Drug: INCB053914
Parts 3 and 4: INCB053914 + AzacitidineExperimentalAzacitidine will be administered at a dose of 75 mg/m2 subcutaneously or via IV per day, as a combination therapy with INCB053914.
Receives: Drug: INCB053914; Drug: Azacitidine
Parts 3 and 4: INCB053914 + I-DAC (Intermediate dose cytarabine)ExperimentalI-DAC (intermediate dose cytarabine) will be administered at a dose of 1 g/m2 per day as an infusion as a combination therapy with INCB053914.
Receives: Drug: INCB053914; Drug: I-DAC (Intermediate dose cytarabine)
Parts 3 and 4: INCB053914 + RuxolitinibExperimentalRuxolitinib will be administered as an oral dose between 5 mg to 25 mg twice per day, as a combination therapy with INCB053914.
Receives: Drug: INCB053914; Drug: Ruxolitinib
Parts 1 and 2: INCB053914 50 mgExperimentalINCB053914 will be self-administered orally twice day in as a 50mg immediate release tablet as a monotherapy.
Receives: Drug: INCB053914
Parts 1 and 2: INB053914 65 mgExperimentalINCB053914 will be self-administered orally twice day in as a 65mg immediate release tablet as a monotherapy.
Receives: Drug: INCB053914
Parts 1 and 2: INB053914 80 mgExperimentalINCB053914 will be self-administered orally twice day in as a 80mg immediate release tablet as a monotherapy.
Receives: Drug: INCB053914
Parts 1 and 2: INB053914 100 mg BIDExperimentalINCB053914 will be self-administered orally twice day in as a 100mg immediate release tablet as a monotherapy.
Receives: Drug: INCB053914
Parts 1 and 2: INB053914 115 mgExperimentalINCB053914 will be self-administered orally twice day in as a 115mg immediate release tablet as a monotherapy.
Receives: Drug: INCB053914

What is being measured

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

  1. Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events

    Measured: Approximately 7 months

  2. Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With the Intermediate-dose Cytarabine (I DAC) in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) Based on Objective Remission Rate (ORR)

    The primary efficacy endpoint of ORR in patients with AML who received INCB053914 in combination with cytarabine in Part 4 was not assessed because Part 4 was not opened for enrollment owing to this combination regimen not being tolerated in Part 3.

    Measured: Approximately 2 months

  3. Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With Azacitidine in Subjects With Newly Diagnosed AML Who Are 65 Years or Older and Unfit for Intensive Chemotherapy Based on ORR

    The primary efficacy endpoint of ORR in patients with AML who received INCB053914 plus azacitidine in Part 4 was not performed due to limited enrollment as a result of early study termination.

    Measured: Approximately 6 months

Secondary outcomes (21)
  1. Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)

    Percent Inhibition of pBAD at the C1D15 trough from the pBAD at pre-dose by ex vivo cellular assay

    Measured: 1 month

  2. Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine

    Measured: Cycle 1 Day 5

  3. Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine

    Measured: Cycle 1 Day 5

  4. Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine

    Measured: Cycle 1 Day 5

  5. Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine

    Measured: Cycle 1 Day 5

  6. Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine

    Measured: Cycle 1 Day 5

  7. Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine

    Measured: Cycle 1 Day 8

  8. Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine

    Measured: Cycle 1 Day 8

  9. Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine

    Measured: Cycle 1 Day 8

  10. Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine

    Measured: Cycle 1 Day 8

  11. Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine

    Measured: Cycle 1 Day 8

  12. Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

    Measured: Regimen 2 Week 4

  13. Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

    Measured: Regimen 2 Week 4

  14. Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

    Measured: Regimen 2 Week 4

  15. Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

    Measured: Regimen 2 Week 4

  16. Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

    Measured: Regimen 2 Week 4

  17. Pharmacokinetics: Tmax of INCB053914 Monotherapy

    Measured: Cycle 1 Day 8

  18. Pharmacokinetics: AUCtau of INCB053914 Monotherapy

    Measured: Cycle 1 Day 8

  19. Pharmacokinetics: CL/F of INCB053914 Monotherapy

    Measured: Cycle 1 Day 8

  20. Pharmacokinetics: Cmax of INCB053914 Monotherapy

    Measured: Cycle 1 Day 8

  21. Pharmacokinetics: Ctau of INCB053914 Monotherapy

    Measured: Cycle 1 Day 8

Timeline

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

  1. First posted27 Oct 2015 (estimated)
  2. Study start29 Dec 2015
  3. Primary completion11 Aug 2020
  4. Study completion11 Aug 2020

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
97 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02587598
Sponsor's protocol ID
INCB 53914-101
Status last verified
Nov 2021
First submitted
26 Oct 2015
Last updated
8 Dec 2021
Data monitoring committee
No
FDA-regulated device
No
Expanded access
Available

Publications

  • Patel MR, Donnellan W, Byrne M, Asch AS, Zeidan AM, Baer MR, Fathi AT, Kuykendall AT, Zheng F, Walker C, Cheng L, Marando C, Savona MR. Phase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies. Clin Lymphoma Myeloma Leuk. 2023 Sep;23(9):674-686. doi: 10.1016/j.clml.2023.05.002. Epub 2023 May 15.

    PubMed 37290996

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing INCB053914, I-DAC (Intermediate dose cytarabine) and Azacitidine in people with Solid Tumors, run by Incyte Corporation at 19 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 14 inclusion and 8 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: stopped early, as of the sponsor's last update on 8 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events (time frame: Approximately 7 months). The study lists 3 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 NCT02587598, which also lists 1 linked publication.

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 8 Dec 2021.

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