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)

Relapsed or Refractory Acute Myeloid Leukemia (AML) Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04113616
• Other study ID #: KRT-232-104
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: September 25, 2019
• Est. completion date: September 27, 2023

Study information

• Verified date: March 2024
• Source: Kartos Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 70
• Est. completion date: September 27, 2023
• Est. primary completion date: September 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myeloproliferative Disorders
• Relapsed or Refractory Acute Myeloid Leukemia (AML)

Intervention

Drug:
• KRT-232
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.
• Cytarabine
Cytarabine is an anti-cancer chemotherapy drug taken via injection.
• Decitabine
Decitabine is an anti-cancer chemotherapy drug taken via injection.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Kartos Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: To determine KRT-232 recommended phase 2 dose (RP2D)	Number of dose-limiting toxicities (DLTs) of KRT-232 in combination with cytarabine or decitabine	28 Days
Primary	Part B: To determine the RP2D of KRT-232	The safety review committee (SRC) will determine the RP2D based on safety and tolerability data obtained from each arm	2 years after last patient enrolled
Secondary	Part A: To determine the rates of complete remission (CR) and complete remission with partial hematological improvement (CRh)	Proportion of patients achieving complete remission (CR) or complete remission with partial hematological improvement (CRh) as determined by Modified 2017 European LeukemiaNet (ELN) response criteria	12 weeks
Secondary	Part B: To determine the rates of complete remission (CR), CR with partial hematological improvement (CRh) and CR with incomplete hematologic recovery (CRi)	Proportion of patients achieving complete remission (CR), complete remission with partial hematological improvement (CRh), and CR with incomplete hematologic recovery (CRi) as determined by Modified 2017 European LeukemiaNet (ELN) response criteria	12 weeks