KRT-232 and TKI Study in Chronic Myeloid Leukemia

NCT04835584 | Recruiting Phase 1 FDA Drug

• 1 other identifier: KRT-232-117
• Study Type: interventional
• Target: 109
• Locations: 8 countries
• Sites: 26

Brief Summary

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with Ph+ Chronic Myeloid Leukemia (CML) who have relapsed or are refractory or intolerant to a Tyrosine Kinase Inhibitor (TKI). This study is a global, open label Phase 1b/2 to determine the efficacy and safety of KRT-232 in patients with chronic phase CML (CML-CP) and accelerated phase (CML-AP) who have failed TKI treatments.

Conditions

Chronic Myeloid Leukemia

Keywords

navtemadlin

Outcome Measures

Primary Outcomes (3)

• Part 1: Maximum tolerated dose (MTD)/maximum administered dose (MAD) of KRT-232

  DLTs will be used to establish the MTD/MAD of KRT-232 in combination with dasatinib or nilotinib

  28 Days

• Part 2, Arm A and B: Major molecular response (MMR) rate

  The proportion of subjects who achieved complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR) according to modified ELN criteria

  6 months

• Part 2, Arm C: Major hematological response (MaHR) rate

  The proportion of subjects who achieved MaHR according to modified ELN criteria

  6 months

Secondary Outcomes (6)

• CCyR rate

  12 months

• MCyR rate

  47 months

• Duration of response

  47 months

• Rate of complete hematologic response (CHR)

  47 months

• Progression-free survival (PFS) in each Arm

  47 months

Study Arms (4)

Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP

EXPERIMENTAL

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. TKI (dasatinib or nilotinib) will be administered orally, per locally prescribed dose and schedule.

Drug: KRT-232; Drug: Dasatinib; Drug: Nilotinib

Part 2, Arm A (KRT-232 combined with Dasatinib in patients with CML-CP)

EXPERIMENTAL

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Dasastinib will be administered orally, per locally prescribed dose and schedule.

Drug: KRT-232; Drug: Dasatinib

Part 2, Arm B (KRT-232 combined with Nilotinib in patients with CML-CP)

EXPERIMENTAL

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Nilotinib will be administered orally, per locally prescribed dose and schedule.

Drug: KRT-232; Drug: Nilotinib

Part 2, Arm C (KRT-232 combined with Dasatinib or Nilotinib in patients with CML-AP)

EXPERIMENTAL

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle. Dasatinib or Nilotinib will be administered orally, per locally prescribed dose and schedule.

Drug: KRT-232; Drug: Dasatinib; Drug: Nilotinib

Interventions

KRT-232 DRUG

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

Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP; Part 2, Arm A (KRT-232 combined with Dasatinib in patients with CML-CP); Part 2, Arm B (KRT-232 combined with Nilotinib in patients with CML-CP); Part 2, Arm C (KRT-232 combined with Dasatinib or Nilotinib in patients with CML-AP)

Dasatinib DRUG

Dasatinib is a Tyrosine Kinase Inhibitor anticancer drug taken by mouth.

Also known as: Dasatinib Zentiva

Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP; Part 2, Arm A (KRT-232 combined with Dasatinib in patients with CML-CP); Part 2, Arm C (KRT-232 combined with Dasatinib or Nilotinib in patients with CML-AP)

Nilotinib DRUG

Nilotinib is an Tyrosine Kinase Inhibitor anticancer drug taken by mouth.

Also known as: Tasigna

Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP; Part 2, Arm B (KRT-232 combined with Nilotinib in patients with CML-CP); Part 2, Arm C (KRT-232 combined with Dasatinib or Nilotinib in patients with CML-AP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase 1b and Phase 2 Arms A and B: Documented TP53wt, Ph+, BCR-ABL+ CML-CP
• Phase 2 Arm C ONLY: Documented TP53wt, Ph+, BCR-ABL+ CML-AP
• Subject is resistant (relapsed or refractory) and/or intolerant to at least 1 prior TKI.
• Adults ≥ 18 years of age.
• ECOG performance status of 0 to 2
• Adequate hematologic, hepatic, and renal functions

You may not qualify if:

• Phase 1b and Phase 2 Arms A and B: Documented Ph+, BCR-ABL+ CML-AP
• Documented Ph+, BCR-ABL+ CML-BC
• Known T315I mutation.
• Prior treatment with MDM2 antagonist therapies.
• Intolerance to current TKI therapy.

Sponsors & Collaborators

• Kartos Therapeutics, Inc.: lead

Study Sites (26)

University of Alabama Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Texas Oncology- Sammons CC at Baylor

Dallas, Texas, 75246, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Princess Margaret Cancer Center

Toronto, Ontario, M5G 2C1, Canada

RECRUITING

Centre Leon Berard

Lyon, 69008, France

RECRUITING

APHM Hopital de la Timone

Marseille, 13005, France

RECRUITING

Institut Paoli-Calmettes

Marseille, 13009, France

RECRUITING

Centre Hospitalier Lyon Sud

Saint-Genis-Laval, 69310, France

RECRUITING

Policlinico di Milano Ospedale Maggiore | Fondazione IRCCS Ca' Granda

Milan, MI, 20122, Italy

RECRUITING

Azienda Ospedaliero - Universitaria Mater Domini

Catanzaro, 88100, Italy

RECRUITING

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori

Meldola FC, 47014, Italy

RECRUITING

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

RECRUITING

Pratia Onkologia Katowice

Katowice, 40-519, Poland

RECRUITING

National Medical Research Center of Hematology

Moscow, 125167, Russia

RECRUITING

Almazov National Medical Research Center

Saint Petersburg, 197341, Russia

RECRUITING

Samara State Medical University

Samara, 443001, Russia

RECRUITING

Kyungpook National University Hospital

Daegu, South Korea

RECRUITING

Samsung Medical Center

Seoul, 135-710, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

Severance Hospital

Seoul, South Korea

RECRUITING

Clínica Universidad de Navarra

Madrid, Navarre, 28027, Spain

RECRUITING

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

navtemadlin; 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid; Dasatinib; nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Central Study Contacts

John Mei

CONTACT

650-542-0136; jmei@kartosthera.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2021
• First Posted: April 8, 2021
• Study Start: May 7, 2021
• Primary Completion: December 31, 2024
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 21, 2022

Record last verified: 2022-03

Locations

PL (1); KR (4); IT (4); ES (4); CA (1); RU (3); FR (4); US (5)