Clinical trial NCT04113616: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 When Administered Alone and in Combination With Low-Dose Cytarabine (LDAC) or Decitabine in Patients With Acute Myeloid Leukemia (AML)
Official title: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 When Administered Alone and in Combination With Low-Dose Cytarabine (LDAC) or Decitabine in Patients With Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Relapsed or Refractory Acute Myeloid Leukemia (AML)
Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN)
Keywords: navtemadlin
Lead sponsor: Kartos Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-10-03
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, when administered alone and in combination with low-dose cytarabine (LDAC) or Decitabine for the treatment of adults with Acute Myeloid Leukemia (AML) and AML secondary to myeloproliferative neoplasms (MPN). Participants must be relapsed/refractory (having failed prior therapy) and will be assigned to receive monotherapy (KRT-232 alone) or combination therapy (KRT-232 with LDAC or KRT-232 with Decitabine).


Eligibility criteria: Key Inclusion Criteria:

* Part A: Patients with relapsed or refractory AML, or newly-diagnosed AML secondary to MPN
* Part B:Patients with relapsed or refractory AML secondary to MPN (myelofibrosis \[MF\], polycythemia vera \[PV\], or essential thrombocythemia \[ET\]); patients may have been treated with ≥1 prior lines of therapy for their AML secondary to MPN.
* Adequate hepatic and renal function
* Appropriate prior treatment with an FLT3 or IDH1/2 inhibitor where applicable

Key Exclusion Criteria:

* Patients who are TP53 mutation positive
* Prior treatment with an MDM2 antagonist therapy
* Patients treated with ≥ 18 g/m2 of cytarabine within the prior 90 days are not eligible to be treated with cytarabine on this study but may be treated with decitabine (for Part A) .
* Patients previously treated with decitabine are not eligible to receive decitabine on this study but may be treated with cytarabine (for Part A) .
* Patients who have received an allogeneic HSCT within 90 days of enrollment or who have active graft-versus-host disease requiring active therapy (for Part A)
* Allogeneic stem cell transplant within 3 months; autologous stem cell transplant within 3 months or active graft-versus-host disease prior to first dose of study treatment (for Part B)
* Patients who have received immunosuppressive therapy for graft-versus-host disease within 1 month prior to enrollment into this study
* Patients who are eligible for an allogeneic HSCT per the opinion of the investigator and have a donor. Patients who are HSCT-eligible in the opinion of the investigator, but who refuse a transplant, are eligible for the study.
* Patients with known CNS involvement with AML, acute promyelocytic leukemia (APL), or a history of bleeding diathesis
* Patients who have had major surgery within 28 days prior to the first treatment with KRT-232
* Women who are pregnant or breastfeeding

Primary outcomes:
measure: Part A: To determine KRT-232 recommended phase 2 dose (RP2D)
timeFrame: 28 Days
measure: Part B: To determine the RP2D of KRT-232
timeFrame: 2 years after last patient enrolled
Secondary outcomes:
measure: Part A: To determine the rates of complete remission (CR) and complete remission with partial hematological improvement (CRh)
timeFrame: 12 weeks
measure: Part B: To determine the rates of complete remission (CR), CR with partial hematological improvement (CRh) and CR with incomplete hematologic recovery (CRi)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: New York
country: United States
facility: Mount Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell
state: New York
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Clayton
country: Australia
facility: Monash Health
city: Kogarah
country: Australia
facility: St. George Hospital
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Waratah
country: Australia
facility: Calvary Mater Newcastle Hospital
city: West Perth
country: Australia
facility: Perth Blood Institute
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: Ghent
country: Belgium
facility: UZ Gent
city: Haine-Saint-Paul
country: Belgium
facility: Centre Hospitalier (CH) Jolimont
city: Turnhout
country: Belgium
facility: AZ Turnhout
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire (CHU) de Bordeaux
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nice
country: France
facility: Centre Hospitalier Universitaire (CHU) de Nice
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Halle
country: Germany
facility: Universitätsklinikum Halle
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Jena
country: Germany
facility: University Hospital Jena
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Lübeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Del-Pesti Centrumkorhaz Orszagos Hematologiai es Infektologi
city: Debrecen
country: Hungary
facility: szabolcs-szatmár-bereg megyei kórházak és egyetemi oktatókórház Jósa András Oktatókórház
city: Kaposvár
country: Hungary
facility: Somogy Megyei KAposi Mor Oktato Korhaz
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Medical Center Ein Kerem
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Tel Aviv
country: Israel
facility: Assaf Harofeh Medical Center AHMC
city: Novara
country: Italy
facility: Universitaria Maggiore della Carità Novara
state: Piemonte
city: Palermo
country: Italy
facility: A.O.O.R. Villa Sofia Cervello
state: Sicilia
city: Bologna
country: Italy
facility: AOU Policlinico S.Orsola-Malpighi
city: Pesaro
country: Italy
facility: AORMN Hospital Hematology and BMT Center
city: Siena
country: Italy
facility: AOUS Le Scotte
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea-Seoul St. Mary's Hospital
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Las Palmas
country: Spain
facility: Hospital Universitario de Gran Canaria Doctor Negrin
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria de Málaga
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Trust, Churchill Hospital
Study officials:
References: