This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05936359
Recruitment Status : Recruiting
First Posted : July 7, 2023
Last Update Posted : April 26, 2024
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
This study is being conducted to evaluate the safety, tolerability, and dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE) of INCA033989 administered as a monotherapy or in combination with ruxolitinib in participants with myeloproliferative neoplasms.

Condition or disease Intervention/treatment Phase
Myeloproliferative Neoplasms Drug: INCA033989 Drug: Ruxolitinib Phase 1

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 225 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Multicenter Study of INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms
Actual Study Start Date : September 25, 2023
Estimated Primary Completion Date : February 29, 2028
Estimated Study Completion Date : February 29, 2028

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Part 1a Dose Escalation Cohort Disease Group A - with MF
INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles as monotherapy to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with myelofibrosis (MF) will enroll in this group.
 Drug: INCA033989
INCA033989 will be administered at protocol defined dose.
Experimental: Part 1a Dose Escalation Cohort Disease Group A - with ET
INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles as monotherapy to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with with essential thrombocythemia (ET) will enroll in this group.
 Drug: INCA033989
INCA033989 will be administered at protocol defined dose.
Experimental: Part 1a: Dose Escalation Cohort Disease Group B - with TGB-MF SubOpt R
INCA033989 will be administered at a protocol defined starting regimen in 28- day cycles and will allow for the evaluation of INCA033989 in combination with ruxolitinib to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with myelofibrosis (MF) exhibiting suboptimal response (SubOpt R) will enroll in this group.
 Drug: INCA033989
INCA033989 will be administered at protocol defined dose.

Drug: Ruxolitinib
Rux will be administered according to Prescribing Information/SmPC.
Other Name: Jakafi
Experimental: Part 1b: Dose Expansion - with MF
INCA033989 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) myelofibrosis MF will enroll in this group.
 Drug: INCA033989
INCA033989 will be administered at protocol defined dose.
Experimental: Part 1b: Dose Expansion - with TGB-MF SubOpt R
INCA033989 will be administered as an add-on therapy in combination with ruxolitinibat at the RDE(s) identified during Part 1a. Participants with treatment Group B (TGB) MF SubOpt R will enroll in this group.
 Drug: INCA033989
INCA033989 will be administered at protocol defined dose.

Drug: Ruxolitinib
Rux will be administered according to Prescribing Information/SmPC.
Other Name: Jakafi
Experimental: Part 1b: Dose Expansion - with ET
INCA033989 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) essential thrombocythemia (ET) will enroll in this group.
 Drug: INCA033989
INCA033989 will be administered at protocol defined dose.
Experimental: Part 1c: Dose Expansion
INCA033989 will be administered at the dose level found to exhibit an overall positive benefit/risk as monotherapy or as combination therapy with Ruxolitinib. Participants with myelofibrosis (MF) will enroll in this group. The participants enrolled in the monotherapy arm will be offered the option to crossover to combination therapy with ruxolitinib if a suboptimal response to monotherapy is observed after 12 weeks.
 Drug: INCA033989
INCA033989 will be administered at protocol defined dose.

Drug: Ruxolitinib
Rux will be administered according to Prescribing Information/SmPC.
Other Name: Jakafi


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Number of participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 28 days ]
    Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.

  2. Number of participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to 3 years and 60 days ]
    Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug monotherapy and in combination with ruxolitinib

  3. Number of participants with TEAEs leading to dose modification or discontinuation [ Time Frame: Up to 3 years and 60 days ]
    Number of participants with TEAEs leading to dose modification or discontinuation.


Secondary Outcome Measures :
  1. Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF [ Time Frame: Up to 3 years and 60 days ]
    Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria.

  2. Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol [ Time Frame: Up to 3 years and 60 days ]
    Defined as percentage of participants with a protocol defined Spleen Volume Reduction.

  3. Participants with MF with symptomatic anemia: Anemia Response [ Time Frame: Up to 3 years and 60 days ]
    For non transfusion-dependent (TD) participants: An Hb increase relative to baseline as defined in the protocol if non-TD at baseline. For TD participants: Achieving transfusion independency (TI) as defined in the protocol.

  4. Participants With ET: Response Rate [ Time Frame: Up to 3 years and 60 days ]
    Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.

  5. Participants With ET: Mean change from baseline of total symptom score (TSS) [ Time Frame: Up to 3 years and 60 days ]
    Mean change of TSS from baseline.

  6. Mean change in disease-related allele burden [ Time Frame: Up to 3 years and 60 days ]
    Mean change in disease-related allele burden.

  7. Pharmacokinetics Parameter: Cmax of INCA33989 [ Time Frame: Up to 3 years and 60 days ]
    Defined as maximum observed plasma concentration of INCA33989.

  8. Pharmacokinetics Parameter: Tmax of INCA033989 [ Time Frame: Up to 3 years and 60 days ]
    Defined as the time to reach the maximum plasma concentration of INCA33989.

  9. Pharmacokinetics Parameter: Cmin of INCA33989 [ Time Frame: Up to 3 years and 60 days ]
    Defined as the minimum observed plasma concentration of INCA33989.

  10. Pharmacokinetics Parameter: AUC(0-t) of INCA33989 [ Time Frame: Up to 3 years and 60 days ]
    Defined as the area under the concentration-time curve up to the last measurable concentration of INCA33989.

  11. Pharmacokinetics Parameter: AUC 0-∞ of INCA33989 [ Time Frame: Up to 3 years and 60 days ]
    Defined as the area under the concentration-time curve from 0 to infinity of INCA33989.

  12. Pharmacokinetics Parameter: CL/F of INCA33989 [ Time Frame: Up to 3 years and 60 days ]
    Defined as the apparent oral dose clearance of INCA33989.

  13. Pharmacokinetics Parameter: Vz/F of INCA33989 [ Time Frame: Up to 3 years and 60 days ]
    Defined as the apparent oral dose volume of distribution of INCA33989.

  14. Pharmacokinetics Parameter: t1/2 of INCA33989 [ Time Frame: Up to 3 years and 60 days ]
    Defined as the apparent terminal phase disposition half-life of INCA33989.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Life expectancy > 6 months.
  • Willingness to undergo a pretreatment and regular on-study BM biopsies and aspirates (as appropriate to disease).
  • Existing documentation from a qualified local laboratory of CALR exon-9 mutation.
  • Participants with MF and ET as defined in the protocol.

Exclusion Criteria:

  • Presence of any hematological malignancy other than ET, PMF, or post-ET MF.
  • Active invasive malignancy over the previous 2 years.
  • Active HBV/HCV, HIV.
  • History of clinically significant or uncontrolled cardiac disease.
  • Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned.
  • Laboratory values outside the Protocol-defined ranges.
  • Participants undergoing treatment with G-CSF, GM-CSF, or TPO-R agonists at any time within 4 weeks before the first dose of study treatment.
  • Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment.
  • Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating agent used to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
  • For TGBs only: Undergoing treatment with a potent/strong inhibitor or inducer of CYP 3A4/5 within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment, or expected to receive such treatment during the study.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT05936359


Contacts
Layout table for location contacts
Contact: Incyte Corporation Call Center (US) 1.855.463.3463 medinfo@incyte.com
Contact: Incyte Corporation Call Center (ex-US) +800 00027423 eumedinfo@incyte.com

Locations
Show Show 29 study locations
Sponsors and Collaborators
Incyte Corporation
Investigators
Layout table for investigator information
Study Director: Incyte Medical Monitor Incyte Corporation
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT05936359    
Other Study ID Numbers: INCA 33989-101
2022-502514-86-00 ( Registry Identifier: EU CT Number )
First Posted: July 7, 2023    Key Record Dates
Last Update Posted: April 26, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Incyte Corporation:
Myeloproliferative Neoplasms
Ruxolitinib
Myelofibrosis
Essential thrombocythemia
CALR mutation
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases