Trial Review

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
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
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Oregon
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
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
Country [16] 0 0
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
State/province [27] 0 0
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
Country [36] 0 0
Spain
State/province [36] 0 0
Barcelona
Country [37] 0 0
Spain
State/province [37] 0 0
Las Palmas
Country [38] 0 0
Spain
State/province [38] 0 0
Madrid
Country [39] 0 0
Spain
State/province [39] 0 0
Málaga
Country [40] 0 0
Spain
State/province [40] 0 0
Salamanca
Country [41] 0 0
Spain
State/province [41] 0 0
Valencia
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Birmingham
Country [43] 0 0
United Kingdom
State/province [43] 0 0
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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04113616