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Clinical Trials/EUCTR2020-002392-35-AT
EUCTR2020-002392-35-ATActive, not recruitingPhase 1

An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 with TL-895 in Subjects with Relapsed/Refractory Myelofibrosis and of KRT-232 in Janus-associated Kinase Inhibitor-Intolerant Myelofibrosis

Kartos Therapeutics, Inc.0 sites51 target enrollmentStarted: February 16, 2021Last updated:
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Conditions

Trial Snapshot

Phase
Phase 1
Status
Active, not recruiting
Enrollment
51
Study OverviewEligibility CriteriaInvestigatorsRecords & IdentifiersSimilar Trials

Study Overview

Brief Summary

No summary available.

Study Design

Study Type
Interventional clinical trial of medicinal product

Eligibility Criteria

Sex
All

Inclusion Criteria

  • •Subjects must meet the following criteria in order to be eligible for the study:
  • •1. Adults =18 years of age and able to provide informed consent.
  • •2. Confirmed diagnosis of primary MF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO) criteria
  • •3. Subjects with TP53 WT MF, defined as tumors that do not harbor deleterious alteration in TP53
  • •4. Palpable spleen measuring =5 cm below the left lower costal margin or spleen volume of =450 cm3 by MRI or CT scan assessment
  • •5. MF symptoms as defined by having at least 2 symptoms with a score of at least 1 each on the MFSAF v4.0
  • •6. High-risk, intermediate-2 risk, or intermediate-1 risk, defined by Dynamic International Prognostic System (DIPSS) or DIPSS-PLUS
  • •7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 according to ECOG performance status criteria
  • •8. Adequate hematological, hepatic, and renal organ function (as per protocol definition and within 7 days [Phase 1b] or 28 days [Phase 2] prior to the first dose of study treatment)
  • •a. Hematologic:
  • •i. Absolute neutrophil count (ANC) =1.0×109/L (Note: ANC eligibility is based on values obtained in the absence of growth factors, ie, 7 days for granulocyte colony-stimulating factor (G-CSF) or 14 days for pegfilgrastim)
  • •ii. Platelet count =50×109/L
  • •iii. Peripheral blood blast count <10%
  • •b. Hepatic:
  • •i. Total bilirubin within normal limits if total bilirubin is >upper limit of normal (ULN), then subjects are eligible if the direct bilirubin is =2.0×ULN, unless Gilbert's Syndrome
  • •ii. Aspartate transaminase/serum glutamic oxaloacetic transaminase and alanine transaminase/serum glutamic pyruvic transaminase =2.5×ULN
  • •i. Estimated creatinine clearance (eCcr) =30 mL/min by Cockcroft Gault.
  • •9. Female subjects of childbearing potential and their male partners, or male subjects who have female partners of childbearing potential must both use a highly effective contraception method during the study. In addition, male subjects must continue to use contraception for 3 months and 1 week after the last dose of study drug and female subjects must continue to use contraception for 1 month and 1 week after the last dose of study drug. A woman is considered of childbearing potential (ie, fertile, following menarche and until becoming post-menopausal) unless permanently sterile.
  • •10. Must have R/R MF following JAK inhibitor treatment that meets either criterion (1) or (2) below:
  • •1. Relapsed defined by one of the following:
  • •a. Spleen volume increase by =25% by radiographic imaging from nadir
  • •b. =100% increase in palpable distance below the left lower costal margin (LLCM), for Baseline splenomegaly of 5 to 10 cm
  • •c. =50% increase in palpable distance below the LLCM, for Baseline splenomegaly of >10 cm
  • •d. Regrowth after achieving complete response
  • •2. Refractory defined by one of the following after receiving =12 weeks of JAK inhibitor treatment:
  • •a. <10% spleen volume reduction by radiographic imaging
  • •b. <30% decrease from Baseline in spleen size by palpation
  • •Are the trial subjects under 18? no
  • •Number of subjects for this age range:
  • •F.1.2 Adults (18-64 years) yes
  • •F.1.2.1 Number of subjects for this age range 26
  • •F.1.3 Elderly (>=65 years) yes
  • •F.1.3.1 Number of subjects for this age range 25

Exclusion Criteria

  • •Subjects who meet any of the following criteria will not be eligible for the study:
  • •1. Treatment with a JAK inhibitor within 21 days of the Screening MRI/CT
  • •2. Prior MDM2 inhibitor therapy or TP53-directed therapy
  • •3. Prior treatment with a BTK, BMX inhibitor
  • •4. Major surgery, chemotherapy, immunomodulating therapy, biologic therapy, or radiation therapy within 28 days prior to the first dose of study treatment; hydroxyurea may be taken within 1 day prior to the first dose of study treatment
  • •5. Participation in another interventional clinical study within the past 28 days of the first dose of study treatment (participation in observational studies is permitted)
  • •6. Prior splenectomy
  • •7. Splenic irradiation within 12 weeks prior to the first dose of study treatment
  • •8. Prior allogeneic stem-cell transplantation or eligible for allogeneic stem cell transplantation in the opinion of the Investigator; subjects that refuse a transplant are eligible for enrollment in this study.
  • •9. Women who are pregnant or breastfeeding
  • •Page 20 of 127
  • •10. History of major organ transplant
  • •11. Uncontrolled intercurrent illness including, but not limited to, clinically significant cardiac disease (New York Heart Association Class III or IV); symptomatic congestive heart failure; unstable angina pectoris; unstable ventricular arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements
  • •12. Subjects with active hepatitis B virus or hepatitis C virus
  • •13. Subjects with known history of human immunodeficiency virus (HIV)
  • •14. Subjects with clinically significant bacterial, fungal, parasitic, or viral infection that requires therapy. Subjects with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
  • •15. Other malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or treated nonmetastatic prostate cancer with normal prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma
  • •16. Grade 2 or higher QTc prolongation (>480 milliseconds per National Cancer Institute Common Terminology of Adverse Events [NCI-CTCAE] version 5.0 criteria)
  • •17. Major hemorrhage or intracranial hemorrhage within 6 months prior to the first dose of study treatment
  • •18. Having history of difficulty swallowing, gastric or small bowel surgery with history of malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the TL-895 or KRT-232
  • •19. Known hypersensitivity to or contraindications to the study drug or any of its excipients, or to required prophylaxis.
  • •20. Persons committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
  • •21. Requires treatment with proton-pump inhibitors (PPIs; eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving PPIs who switch to H2-receptor antagonists or antacids at least 3 days before Cycle 1 Day 1 are eligible for enrollment in this study

Investigators

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