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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04113616




Registration number
NCT04113616
Ethics application status
Date submitted
1/10/2019
Date registered
3/10/2019
Date last updated
22/03/2024

Titles & IDs
Public 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)
Scientific 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)
Secondary ID [1] 0 0
KRT-232-104
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed or Refractory Acute Myeloid Leukemia (AML) 0 0
Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - KRT-232
Treatment: Drugs - Cytarabine
Treatment: Drugs - Decitabine

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.

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.

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.

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

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.

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.


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

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

Treatment: Drugs: Decitabine
Decitabine is an anti-cancer chemotherapy drug taken via injection.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A: To determine KRT-232 recommended phase 2 dose (RP2D)
Timepoint [1] 0 0
28 Days
Primary outcome [2] 0 0
Part B: To determine the RP2D of KRT-232
Timepoint [2] 0 0
2 years after last patient enrolled
Secondary outcome [1] 0 0
Part A: To determine the rates of complete remission (CR) and complete remission with partial hematological improvement (CRh)
Timepoint [1] 0 0
12 weeks
Secondary outcome [2] 0 0
Part B: To determine the rates of complete remission (CR), CR with partial hematological improvement (CRh) and CR with incomplete hematologic recovery (CRi)
Timepoint [2] 0 0
12 weeks

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/09/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/09/2023
Sample size
Target
Accrual to date
Final
70
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Monash Health - Clayton
Recruitment hospital [2] 0 0
St. George Hospital - Kogarah
Recruitment hospital [3] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [4] 0 0
Calvary Mater Newcastle Hospital - Waratah
Recruitment hospital [5] 0 0
Perth Blood Institute - West Perth
Recruitment postcode(s) [1] 0 0
- Clayton
Recruitment postcode(s) [2] 0 0
- Kogarah
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment postcode(s) [4] 0 0
2298 - Waratah
Recruitment postcode(s) [5] 0 0
6005 - West Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
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United States of America
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Maryland
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United States of America
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New York
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United States of America
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Ohio
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United States of America
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Oregon
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United States of America
State/province [6] 0 0
Texas
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Belgium
State/province [7] 0 0
Anderlecht
Country [8] 0 0
Belgium
State/province [8] 0 0
Brussels
Country [9] 0 0
Belgium
State/province [9] 0 0
Ghent
Country [10] 0 0
Belgium
State/province [10] 0 0
Haine-Saint-Paul
Country [11] 0 0
Belgium
State/province [11] 0 0
Turnhout
Country [12] 0 0
France
State/province [12] 0 0
Bordeaux
Country [13] 0 0
France
State/province [13] 0 0
Marseille
Country [14] 0 0
France
State/province [14] 0 0
Nice
Country [15] 0 0
France
State/province [15] 0 0
Paris
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Germany
State/province [16] 0 0
Halle
Country [17] 0 0
Germany
State/province [17] 0 0
Hamburg
Country [18] 0 0
Germany
State/province [18] 0 0
Jena
Country [19] 0 0
Germany
State/province [19] 0 0
Leipzig
Country [20] 0 0
Germany
State/province [20] 0 0
Lübeck
Country [21] 0 0
Hungary
State/province [21] 0 0
Budapest
Country [22] 0 0
Hungary
State/province [22] 0 0
Debrecen
Country [23] 0 0
Hungary
State/province [23] 0 0
Kaposvár
Country [24] 0 0
Israel
State/province [24] 0 0
Haifa
Country [25] 0 0
Israel
State/province [25] 0 0
Jerusalem
Country [26] 0 0
Israel
State/province [26] 0 0
Ramat Gan
Country [27] 0 0
Israel
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Tel Aviv
Country [28] 0 0
Italy
State/province [28] 0 0
Piemonte
Country [29] 0 0
Italy
State/province [29] 0 0
Sicilia
Country [30] 0 0
Italy
State/province [30] 0 0
Bologna
Country [31] 0 0
Italy
State/province [31] 0 0
Pesaro
Country [32] 0 0
Italy
State/province [32] 0 0
Siena
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Busan
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Seoul
Country [35] 0 0
Poland
State/province [35] 0 0
Gdansk
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Spain
State/province [36] 0 0
Barcelona
Country [37] 0 0
Spain
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Las Palmas
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Spain
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Madrid
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Spain
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Málaga
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Spain
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Salamanca
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Spain
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Valencia
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United Kingdom
State/province [42] 0 0
Birmingham
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United Kingdom
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Cardiff
Country [44] 0 0
United Kingdom
State/province [44] 0 0
London
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Kartos Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT04113616
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04113616