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Study of INCB053914 in Subjects With Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT02587598
Recruitment Status : Recruiting
First Posted : October 27, 2015
Last Update Posted : January 4, 2019
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Brief 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. 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).

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: INCB053914 Drug: I-DAC (Intermediate dose cytarabine) Drug: Azacitidine Drug: Ruxolitinib Phase 1 Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 270 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of INCB053914 in Subjects With Advanced Malignancies
Actual Study Start Date : October 2015
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020


Arm Intervention/treatment
Experimental: INCB053914
Monotherapy
Drug: INCB053914

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.


Experimental: INCB053914 + Azacitidine Drug: INCB053914
Initial cohort dose of INCB053914 at the protocol-specified starting dose. INCB053914 tablets to be administered by mouth.

Drug: Azacitidine
Azacitidine dose will be 75 mg/m^2. Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).
Other Name: Vidaza®

Experimental: INCB053914 + I-DAC Drug: INCB053914
Initial cohort dose of INCB053914 at the protocol-specified starting dose. INCB053914 tablets to be administered by mouth.

Drug: I-DAC (Intermediate dose cytarabine)
Cytarabine dose will be 1 g/m^2. Cytarabine will be administered as an intravenous (IV) infusion.

Experimental: INCB053914 + Ruxolitinib Drug: INCB053914
Initial cohort dose of INCB053914 at the protocol-specified starting dose. INCB053914 tablets to be administered by mouth.

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




Primary Outcome Measures :
  1. Determination of the safety and tolerability of INCB053914 as measured by the number of participants with adverse events [ Time Frame: Approximately 24 months ]
  2. Part 4 only: Determination of the initial efficacy of INCB053914 in combination with select SOC agents as measured by the Objective Remission Rate (ORR) [ Time Frame: Approximately 24 months ]
    ORR is defined as proportion of subjects who achieve complete remission (CR) or CR with incomplete hematologic recovery (CRi]) in subjects with AML.

  3. 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) [ Time Frame: Approximately 24 months ]
  4. 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 [ Time Frame: Approximately 24 months ]

Secondary Outcome Measures :
  1. Plasma concentrations oF INCB053914 will be determined by the use of validated assays [ Time Frame: Cycle 1, Cycle 2 (Part 2 food-effect cohort only), approximately 24 months ]
  2. Objective Remission Rate (ORR) of INCB053914 in subjects with measurable disease [ Time Frame: Baseline through end of study, approximately 24 months ]
  3. Part 4 only: Change and percentage change in spleen volume from baseline through Week 12 measured by MRI or CT in applicable subjects [ Time Frame: Baseline through end of study, approximately 24 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

    • 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.

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02587598


Contacts
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Contact: Incyte Corporation Call Center 1.855.463.3463

  Show 24 Study Locations
Sponsors and Collaborators
Incyte Corporation
Investigators
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Study Director: Fred Zheng, M.D. Incyte Corporation

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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT02587598     History of Changes
Other Study ID Numbers: INCB 53914-101
First Posted: October 27, 2015    Key Record Dates
Last Update Posted: January 4, 2019
Last Verified: January 2019
Keywords provided by Incyte Corporation:
leukemia
myelodysplastic syndrome (MDS)
myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
myelofibrosis (MF)
lymphoproliferative disorders
acute myeloid leukemia (AML)
lymphomas
multiple myeloma (MM)
PIM kinases
Additional relevant MeSH terms:
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Neoplasms
Cytarabine
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors