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)

NCT ID: NCT04113616

Last Updated: 2024-03-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-25

Study Completion Date

2023-09-27

Brief Summary

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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).

Detailed Description

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Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part A - Arm 1

KRT-232+LDAC:

KRT-232 will be administered orally, once daily (QD), on Days 1-7 in combination with LDAC administered at 20 mg/m2/day subcutaneously on Days 1-10 in a 28-day cycle.

Group Type EXPERIMENTAL

KRT-232

Intervention Type DRUG

KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.

Cytarabine

Intervention Type DRUG

Cytarabine is an anti-cancer chemotherapy drug taken via injection.

Part A - Arm 2

KRT-232(7-Day)+Decitabine:

KRT-232 will be administered orally, once daily (QD), on Days 1-7 in combination with Decitabine administered at 20 mg/m2/day intravenously on Days 1-5 in a 28-day cycle.

Group Type EXPERIMENTAL

KRT-232

Intervention Type DRUG

KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.

Decitabine

Intervention Type DRUG

Decitabine is an anti-cancer chemotherapy drug taken via injection.

Part A - Arm 3

KRT-232(14-Day)+Decitabine:

KRT-232 will be administered orally, once daily (QD), on Days 1-7 and Days 15-21 (7 days on/7 days off/7 days on/7 days off) in combination with Decitabine administered at 20 mg/m2/day intravenously on Days 1-5 in a 28-day cycle.

Group Type EXPERIMENTAL

KRT-232

Intervention Type DRUG

KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.

Decitabine

Intervention Type DRUG

Decitabine is an anti-cancer chemotherapy drug taken via injection.

Part B - Arm 1

KRT-232 administered at 360 mg orally, once daily (QD) on Days 1-7 with 21 days off on a 28-day treatment cycle

Group Type EXPERIMENTAL

KRT-232

Intervention Type DRUG

KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.

Part B - Arm 2

KRT-232 administered at 360 mg orally, once daily (QD) on Days 1-7 with 21 days off on a 28-day treatment cycle in Cycle 1, followed by 240 mg orally, once daily (QD) on Days 1-7 with 21 days off on a 28-day cycle, in the subsequent cycles.

Group Type EXPERIMENTAL

KRT-232

Intervention Type DRUG

KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.

Part B - Arm 3

KRT-232 administered at 180 mg orally, once daily (QD) on Days 1-7 with 14 days off on a 21-day treatment cycle.

Group Type EXPERIMENTAL

KRT-232

Intervention Type DRUG

KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.

Interventions

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KRT-232

KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.

Intervention Type DRUG

Cytarabine

Cytarabine is an anti-cancer chemotherapy drug taken via injection.

Intervention Type DRUG

Decitabine

Decitabine is an anti-cancer chemotherapy drug taken via injection.

Intervention Type DRUG

Other Intervention Names

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cytosine arabinoside Cytosar-U Depocyt Arabinosylcytosine Ara-C Dacogen

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kartos Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Mount Sinai

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Weill Cornell

New York, New York, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Monash Health

Clayton, , Australia

Site Status

St. George Hospital

Kogarah, , Australia

Site Status

Royal Perth Hospital

Perth, , Australia

Site Status

Calvary Mater Newcastle Hospital

Waratah, , Australia

Site Status

Perth Blood Institute

West Perth, , Australia

Site Status

Institut Jules Bordet

Anderlecht, , Belgium

Site Status

Cliniques universitaires Saint-Luc

Brussels, , Belgium

Site Status

UZ Gent

Ghent, , Belgium

Site Status

Centre Hospitalier (CH) Jolimont

Haine-Saint-Paul, , Belgium

Site Status

AZ Turnhout

Turnhout, , Belgium

Site Status

Centre Hospitalier Universitaire (CHU) de Bordeaux

Bordeaux, , France

Site Status

Institut Paoli Calmettes

Marseille, , France

Site Status

Centre Hospitalier Universitaire (CHU) de Nice

Nice, , France

Site Status

Hôpital Saint-Louis

Paris, , France

Site Status

Universitätsklinikum Halle

Halle, , Germany

Site Status

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status

University Hospital Jena

Jena, , Germany

Site Status

Universitätsklinikum Leipzig

Leipzig, , Germany

Site Status

Universitaetsklinikum Schleswig-Holstein

Lübeck, , Germany

Site Status

Semmelweis Egyetem

Budapest, , Hungary

Site Status

Del-Pesti Centrumkorhaz Orszagos Hematologiai es Infektologi

Budapest, , Hungary

Site Status

szabolcs-szatmár-bereg megyei kórházak és egyetemi oktatókórház Jósa András Oktatókórház

Debrecen, , Hungary

Site Status

Somogy Megyei KAposi Mor Oktato Korhaz

Kaposvár, , Hungary

Site Status

Rambam Health Care Campus

Haifa, , Israel

Site Status

Hadassah Medical Center Ein Kerem

Jerusalem, , Israel

Site Status

The Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status

Assaf Harofeh Medical Center AHMC

Tel Aviv, , Israel

Site Status

Universitaria Maggiore della Carità Novara

Novara, Piedmont, Italy

Site Status

A.O.O.R. Villa Sofia Cervello

Palermo, Sicily, Italy

Site Status

AOU Policlinico S.Orsola-Malpighi

Bologna, , Italy

Site Status

AORMN Hospital Hematology and BMT Center

Pesaro, , Italy

Site Status

AOUS Le Scotte

Siena, , Italy

Site Status

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Site Status

Inje University Busan Paik Hospital

Busan, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

The Catholic University of Korea-Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Universitario de Gran Canaria Doctor Negrin

Las Palmas, , Spain

Site Status

MD Anderson Cancer Center

Madrid, , Spain

Site Status

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario Virgen de la Victoria de Málaga

Málaga, , Spain

Site Status

Hospital Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Site Status

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

University Hospital of Wales

Cardiff, , United Kingdom

Site Status

The Royal Marsden Hospital

London, , United Kingdom

Site Status

Oxford University Hospitals NHS Trust, Churchill Hospital

Oxford, , United Kingdom

Site Status

Countries

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United States Australia Belgium France Germany Hungary Israel Italy Poland South Korea Spain United Kingdom

Other Identifiers

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KRT-232-104

Identifier Type: -

Identifier Source: org_study_id

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