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)

March 21, 2024 updated by: Kartos Therapeutics, Inc.
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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
      • Clayton, Australia
        • Monash Health
      • Kogarah, Australia
        • St. George Hospital
      • Perth, Australia, 6000
        • Royal Perth Hospital
      • Waratah, Australia, 2298
        • Calvary Mater Newcastle Hospital
      • West Perth, Australia, 6005
        • Perth Blood Institute
  • Belgium
      • Anderlecht, Belgium, 1070
        • Institut Jules Bordet
      • Brussels, Belgium
        • Cliniques universitaires Saint-Luc
      • Ghent, Belgium
        • UZ Gent
      • Haine-Saint-Paul, Belgium, 7100
        • Centre Hospitalier (CH) Jolimont
      • Turnhout, Belgium
        • Az Turnhout
  • France
      • Bordeaux, France, 33000
        • Centre Hospitalier Universitaire (CHU) de Bordeaux
      • Marseille, France, 13009
        • Institut Paoli Calmettes
      • Nice, France, 06000
        • Centre Hospitalier Universitaire (CHU) de Nice
      • Paris, France
        • Hôpital Saint-Louis
  • Germany
      • Halle, Germany
        • Universitätsklinikum Halle
      • Hamburg, Germany
        • Universitatsklinikum Hamburg-Eppendorf
      • Jena, Germany, 07747
        • University Hospital Jena
      • Leipzig, Germany
        • Universitätsklinikum Leipzig
      • Lübeck, Germany
        • Universitaetsklinikum Schleswig-Holstein
  • Hungary
      • Budapest, Hungary, 1085
        • Semmelweis Egyetem
      • Budapest, Hungary
        • Del-Pesti Centrumkorhaz Orszagos Hematologiai es Infektologi
      • Debrecen, Hungary
        • szabolcs-szatmár-bereg megyei kórházak és egyetemi oktatókórház Jósa András Oktatókórház
      • Kaposvár, Hungary, 7400
        • Somogy Megyei Kaposi Mór Oktató Kórház
  • Israel
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus
      • Jerusalem, Israel
        • Hadassah Medical Center Ein Kerem
      • Ramat Gan, Israel, 5265601
        • The Chaim Sheba Medical Center
      • Tel Aviv, Israel, 6423906
        • Tel-Aviv Sourasky Medical Center
      • Tel Aviv, Israel
        • Assaf Harofeh Medical Center AHMC
  • Italy
      • Bologna, Italy
        • AOU Policlinico S.Orsola-Malpighi
      • Pesaro, Italy
        • AORMN Hospital Hematology and BMT Center
      • Siena, Italy, 53100
        • AOUS Le Scotte
    • Piemonte
      • Novara, Piemonte, Italy, 28100
        • Universitaria Maggiore della Carità Novara
    • Sicilia
      • Palermo, Sicilia, Italy, 90146
        • A.O.O.R. Villa Sofia Cervello
  • Korea, Republic of
      • Busan, Korea, Republic of
        • Inje University Busan Paik Hospital
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of
        • Samsung Medical Center
      • Seoul, Korea, Republic of
        • The Catholic University of Korea-Seoul St. Mary's Hospital
  • Poland
      • Gdańsk, Poland
        • Uniwersyteckie Centrum Kliniczne
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Las Palmas, Spain, 35010
        • Hospital Universitario de Gran Canaria Doctor Negrín
      • Madrid, Spain, 28034
        • Hospital Universitario Ramón y Cajal
      • Madrid, Spain
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28033
        • MD Anderson Cancer Center
      • Málaga, Spain, 29010
        • Hospital Universitario Virgen de la Victoria de Málaga
      • Salamanca, Spain, 37007
        • Hospital Universitario de Salamanca
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario de Valencia
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Hospital Universitari Germans Trias i Pujol
  • United Kingdom
      • Birmingham, United Kingdom
        • Birmingham Heartlands Hospital
      • Cardiff, United Kingdom
        • University Hospital of Wales
      • London, United Kingdom, SW3 6JJ
        • The Royal Marsden Hospital
      • Oxford, United Kingdom
        • Oxford University Hospitals NHS Trust, Churchill Hospital
  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10029
        • Mount Sinai
      • New York, New York, United States, 10065
        • Weill Cornell
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.
Drug: Cytarabine
Cytarabine is an anti-cancer chemotherapy drug taken via injection.
Other Names:
  • Ara-C
  • Arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
  • Depocyt
Experimental: 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.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.
Drug: Decitabine
Decitabine is an anti-cancer chemotherapy drug taken via injection.
Other Names:
  • Dacogen
Experimental: 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.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.
Drug: Decitabine
Decitabine is an anti-cancer chemotherapy drug taken via injection.
Other Names:
  • Dacogen
Experimental: 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
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.
Experimental: 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.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.
Experimental: 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.
Drug: KRT-232
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: To determine KRT-232 recommended phase 2 dose (RP2D)
Time Frame: 28 Days
Number of dose-limiting toxicities (DLTs) of KRT-232 in combination with cytarabine or decitabine
28 Days
Part B: To determine the RP2D of KRT-232
Time Frame: 2 years after last patient enrolled
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: To determine the rates of complete remission (CR) and complete remission with partial hematological improvement (CRh)
Time Frame: 12 weeks
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
Part B: To determine the rates of complete remission (CR), CR with partial hematological improvement (CRh) and CR with incomplete hematologic recovery (CRi)
Time Frame: 12 weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kartos Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 25, 2019

Primary Completion (Actual)

September 27, 2023

Study Completion (Actual)

September 27, 2023

Study Registration Dates

First Submitted

October 1, 2019

First Submitted That Met QC Criteria

October 1, 2019

First Posted (Actual)

October 3, 2019

Study Record Updates

Last Update Posted (Actual)

March 22, 2024

Last Update Submitted That Met QC Criteria

March 21, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KRT-232-104

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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