Clinical trial NCT04878003: Study of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis
Official title: An Open-Label, Multicenter, Phase 2 Study Assessing the Safety and Efficacy of KRT-232 or TL-895 in Janus Associated Kinase Inhibitor Treatment-Naïve Myelofibrosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Primary Myelofibrosis (PMF)
Post-Polycythemia Vera Myelofibrosis (Post-PV-MF)
Post-Essential Thrombocythemia Myelofibrosis (Post-ET-MF)
Keywords: navtemadlin
Lead sponsor: Kartos Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-05-07
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates either KRT-232 or TL-895 in treatment naïve patients with myelofibrosis (MF)

The study will be conducted in 2 stages. Stage 1 will evaluate safety, tolerability, and efficacy of either KRT-232 (Arm 1) or TL-895 (Arm 2) in treatment naïve patients. Stage 2 will expand enrollment in Arm 1 and/or Arm 2 if expansion criteria is met.


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
* High-risk, or intermediate-1 and 2 risk, defined by Dynamic International Prognostic System (DIPSS)
* ECOG of 0 or 1

Exclusion Criteria:

* Subjects who are positive for p53 mutation (Arm 1)
* Prior MDM2 inhibitor therapy or p53-directed therapy (Arm 1)
* Prior treatment with any JAK inhibitor
* Prior splenectomy
* Splenic irradiation within 24 weeks prior to randomization
* Prior allogeneic stem-cell transplantation or plans for allogeneic stem-cell transplant
* History of major organ transplant
* Grade 2 or higher QTc prolongation
* Major hemorrhage or intracranial hemorrhage within 24 weeks prior to randomization

Primary outcomes:
measure: Spleen Volume Reduction (SVR)
timeFrame: 24 weeks
Secondary outcomes:
measure: Improvement in Total Symptom Score (TSS)
timeFrame: 24 weeks
measure: Spleen Response Duration
timeFrame: 48 months
measure: Rate of conversion from RBC transfusion dependent to independent
timeFrame: 24 weeks
measure: Overall Survival (OS)
timeFrame: 48 months
measure: Progression free survival (PFS)
timeFrame: 48 months
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Belarus
country: Belarus
facility: Republican Scientific Practical Center of Radiation Medicine and Human Ecology
city: Minsk
country: Belarus
facility: Minsk Scientific and Practice Center of Surgery, Transplantology and Hematology
city: Pleven
country: Bulgaria
facility: UMHAT Georgi Stranski
city: Plovdiv
country: Bulgaria
facility: Medical Centre Hipokrat N
city: Sofia
country: Bulgaria
facility: UMHAT Sv. Ivan Rilski EAD
city: Sofia
country: Bulgaria
facility: Military Medical Academy
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Hematologic Diseases
city: Kutaisi
country: Georgia
facility: JSC EVEX Hospitals
city: Tbilisi
country: Georgia
facility: LTD M.Zodelava Hematology Centre
city: Tbilisi
country: Georgia
facility: K.Eristavi National Center of Experimental and Clinical Surgery
city: Aguascalientes
country: Mexico
facility: Centro de Investigacion Medica Aquascalientes (CIMA)
city: Chihuahua
country: Mexico
facility: Unidad de Investigacion CIMA SC
city: Oaxaca
country: Mexico
facility: Centro de Investigacion Clinica de Oaxaca (CICLO)
city: Veracruz
country: Mexico
facility: Sociedad de Metabolismo Y Corazon - SOMECO
city: Katowice
country: Poland
facility: Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich
city: Opole
country: Poland
facility: Szpital Wojewodzki w Opolu Sp. z o.o., Oddzial Hematologii i Onkologii Hematologicznej
city: Słupsk
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.
city: Moscow
country: Russian Federation
facility: Botkin City Clinical Hospital
city: Petrozavodsk
country: Russian Federation
facility: Republican Hospital n.a. V.A. Baranov
city: Saint Petersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University
city: Saint Petersburg
country: Russian Federation
facility: Almazov National Medical Research Center
city: Saint Petersburg
country: Russian Federation
facility: Almazov National Medical Research Centre
city: Samara
country: Russian Federation
facility: Samara State Medical University
city: Soweto
country: South Africa
facility: Wits Baragwanath Clinical Hematology Department
city: Dnipro
country: Ukraine
facility: City Hematology Center of Municipal Non-Profit Enterprise City Clinical Hospital #4 of Dnipro City Council
Study officials:
References: