Back to resultsAn 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)
Primary Purpose
Relapsed or Refractory Acute Myeloid Leukemia (AML), Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN)
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
KRT-232
Cytarabine
Decitabine
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed or Refractory Acute Myeloid Leukemia (AML) focused on measuring navtemadlin
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
Sites / Locations
- University of Chicago
- University of Maryland Medical Center
- Mount Sinai
- Memorial Sloan Kettering Cancer Center
- Weill Cornell
- The Ohio State University
- Oregon Health and Science University
- MD Anderson Cancer Center
- Monash Health
- St. George Hospital
- Royal Perth Hospital
- Calvary Mater Newcastle Hospital
- Perth Blood Institute
- Institut Jules Bordet
- Cliniques universitaires Saint-Luc
- UZ Gent
- Centre Hospitalier (CH) Jolimont
- AZ Turnhout
- Centre Hospitalier Universitaire (CHU) de Bordeaux
- Institut Paoli Calmettes
- Centre Hospitalier Universitaire (CHU) de Nice
- Hôpital Saint-Louis
- Universitätsklinikum Halle
- Universitätsklinikum Hamburg-Eppendorf
- University Hospital Jena
- Universitätsklinikum Leipzig
- Universitaetsklinikum Schleswig-Holstein
- Semmelweis Egyetem
- Del-Pesti Centrumkorhaz Orszagos Hematologiai es Infektologi
- szabolcs-szatmár-bereg megyei kórházak és egyetemi oktatókórház Jósa András Oktatókórház
- Somogy Megyei KAposi Mor Oktato Korhaz
- Rambam Health Care Campus
- Hadassah Medical Center Ein Kerem
- The Chaim Sheba Medical Center
- Tel-Aviv Sourasky Medical Center
- Assaf Harofeh Medical Center AHMC
- Universitaria Maggiore della Carità Novara
- A.O.O.R. Villa Sofia Cervello
- AOU Policlinico S.Orsola-Malpighi
- AORMN Hospital Hematology and BMT Center
- AOUS Le Scotte
- Inje University Busan Paik Hospital
- Seoul National University Hospital
- Samsung Medical Center
- The Catholic University of Korea-Seoul St. Mary's Hospital
- Uniwersyteckie Centrum Kliniczne
- Hospital Universitari Germans Trias i Pujol
- Hospital Universitari Vall d'Hebron
- Hospital Universitario de Gran Canaria Doctor Negrin
- MD Anderson Cancer Center
- Hospital Universitario Ramon y Cajal
- Hospital Universitario 12 de Octubre
- Hospital Universitario Virgen de la Victoria de Málaga
- Hospital Universitario de Salamanca
- Hospital Clínico Universitario de Valencia
- Birmingham Heartlands Hospital
- University Hospital of Wales
- The Royal Marsden Hospital
- Oxford University Hospitals NHS Trust, Churchill Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Part A - Arm 1
Part A - Arm 2
Part A - Arm 3
Part B - Arm 1
Part B - Arm 2
Part B - Arm 3
Arm Description
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.
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.
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.
KRT-232 administered at 360 mg orally, once daily (QD) on Days 1-7 with 21 days off on a 28-day treatment cycle
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.
KRT-232 administered at 180 mg orally, once daily (QD) on Days 1-7 with 14 days off on a 21-day treatment cycle.
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
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
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
Full Information
NCT ID
NCT04113616
First Posted
October 1, 2019
Last Updated
July 31, 2023
Sponsor
Kartos Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04113616
Brief 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)
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
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 25, 2019 (Actual)
Primary Completion Date
December 15, 2023 (Anticipated)
Study Completion Date
July 15, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kartos Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed or Refractory Acute Myeloid Leukemia (AML), Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN)
Keywords
navtemadlin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
86 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Part A - Arm 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Part A - Arm 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Part A - Arm 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Part B - Arm 1
Arm Type
Experimental
Arm Description
KRT-232 administered at 360 mg orally, once daily (QD) on Days 1-7 with 21 days off on a 28-day treatment cycle
Arm Title
Part B - Arm 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Part B - Arm 3
Arm Type
Experimental
Arm Description
KRT-232 administered at 180 mg orally, once daily (QD) on Days 1-7 with 14 days off on a 21-day treatment cycle.
Intervention Type
Drug
Intervention Name(s)
KRT-232
Intervention Description
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
cytosine arabinoside, Cytosar-U, Depocyt, Arabinosylcytosine, Ara-C
Intervention Description
Cytarabine is an anti-cancer chemotherapy drug taken via injection.
Intervention Type
Drug
Intervention Name(s)
Decitabine
Other Intervention Name(s)
Dacogen
Intervention Description
Decitabine is an anti-cancer chemotherapy drug taken via injection.
Primary Outcome Measure Information:
Title
Part A: To determine KRT-232 recommended phase 2 dose (RP2D)
Description
Number of dose-limiting toxicities (DLTs) of KRT-232 in combination with cytarabine or decitabine
Time Frame
28 Days
Title
Part B: To determine the RP2D of KRT-232
Description
The safety review committee (SRC) will determine the RP2D based on safety and tolerability data obtained from each arm
Time Frame
2 years after last patient enrolled
Secondary Outcome Measure Information:
Title
Part A: To determine the rates of complete remission (CR) and complete remission with partial hematological improvement (CRh)
Description
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
Time Frame
12 weeks
Title
Part B: To determine the rates of complete remission (CR), CR with partial hematological improvement (CRh) and CR with incomplete hematologic recovery (CRi)
Description
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
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Weill Cornell
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Monash Health
City
Clayton
Country
Australia
Facility Name
St. George Hospital
City
Kogarah
Country
Australia
Facility Name
Royal Perth Hospital
City
Perth
ZIP/Postal Code
6000
Country
Australia
Facility Name
Calvary Mater Newcastle Hospital
City
Waratah
ZIP/Postal Code
2298
Country
Australia
Facility Name
Perth Blood Institute
City
West Perth
ZIP/Postal Code
6005
Country
Australia
Facility Name
Institut Jules Bordet
City
Anderlecht
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Cliniques universitaires Saint-Luc
City
Brussels
Country
Belgium
Facility Name
UZ Gent
City
Ghent
Country
Belgium
Facility Name
Centre Hospitalier (CH) Jolimont
City
Haine-Saint-Paul
ZIP/Postal Code
7100
Country
Belgium
Facility Name
AZ Turnhout
City
Turnhout
Country
Belgium
Facility Name
Centre Hospitalier Universitaire (CHU) de Bordeaux
City
Bordeaux
ZIP/Postal Code
33000
Country
France
Facility Name
Institut Paoli Calmettes
City
Marseille
ZIP/Postal Code
13009
Country
France
Facility Name
Centre Hospitalier Universitaire (CHU) de Nice
City
Nice
ZIP/Postal Code
06000
Country
France
Facility Name
Hôpital Saint-Louis
City
Paris
Country
France
Facility Name
Universitätsklinikum Halle
City
Halle
Country
Germany
Facility Name
Universitätsklinikum Hamburg-Eppendorf
City
Hamburg
Country
Germany
Facility Name
University Hospital Jena
City
Jena
ZIP/Postal Code
07747
Country
Germany
Facility Name
Universitätsklinikum Leipzig
City
Leipzig
Country
Germany
Facility Name
Universitaetsklinikum Schleswig-Holstein
City
Lübeck
Country
Germany
Facility Name
Semmelweis Egyetem
City
Budapest
ZIP/Postal Code
1085
Country
Hungary
Facility Name
Del-Pesti Centrumkorhaz Orszagos Hematologiai es Infektologi
City
Budapest
Country
Hungary
Facility Name
szabolcs-szatmár-bereg megyei kórházak és egyetemi oktatókórház Jósa András Oktatókórház
City
Debrecen
Country
Hungary
Facility Name
Somogy Megyei KAposi Mor Oktato Korhaz
City
Kaposvár
ZIP/Postal Code
7400
Country
Hungary
Facility Name
Rambam Health Care Campus
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Hadassah Medical Center Ein Kerem
City
Jerusalem
Country
Israel
Facility Name
The Chaim Sheba Medical Center
City
Ramat Gan
ZIP/Postal Code
5265601
Country
Israel
Facility Name
Tel-Aviv Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Facility Name
Assaf Harofeh Medical Center AHMC
City
Tel Aviv
Country
Israel
Facility Name
Universitaria Maggiore della Carità Novara
City
Novara
State/Province
Piemonte
ZIP/Postal Code
28100
Country
Italy
Facility Name
A.O.O.R. Villa Sofia Cervello
City
Palermo
State/Province
Sicilia
ZIP/Postal Code
90146
Country
Italy
Facility Name
AOU Policlinico S.Orsola-Malpighi
City
Bologna
Country
Italy
Facility Name
AORMN Hospital Hematology and BMT Center
City
Pesaro
Country
Italy
Facility Name
AOUS Le Scotte
City
Siena
ZIP/Postal Code
53100
Country
Italy
Facility Name
Inje University Busan Paik Hospital
City
Busan
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
The Catholic University of Korea-Seoul St. Mary's Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Uniwersyteckie Centrum Kliniczne
City
Gdańsk
Country
Poland
Facility Name
Hospital Universitari Germans Trias i Pujol
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario de Gran Canaria Doctor Negrin
City
Las Palmas
ZIP/Postal Code
35010
Country
Spain
Facility Name
MD Anderson Cancer Center
City
Madrid
ZIP/Postal Code
28033
Country
Spain
Facility Name
Hospital Universitario Ramon y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Virgen de la Victoria de Málaga
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Hospital Clínico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Birmingham Heartlands Hospital
City
Birmingham
Country
United Kingdom
Facility Name
University Hospital of Wales
City
Cardiff
Country
United Kingdom
Facility Name
The Royal Marsden Hospital
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
Oxford University Hospitals NHS Trust, Churchill Hospital
City
Oxford
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
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)
We'll reach out to this number within 24 hrs