Relapsed or Refractory Acute Myeloid Leukemia (AML)Phase 1/2NCT04113616
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)
A Phase 1/2 study testing KRT-232, Cytarabine and Decitabine in people with Relapsed or Refractory Acute Myeloid Leukemia (AML) and Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN), run by Kartos Therapeutics, Inc. at 59 sites in 12 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Acute Myeloid Leukemia (AML), Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN)
- What is being tested?
- KRT-232, Cytarabine and Decitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 59 sitesin 12 countries
- Study dates
- 25 Sep 2019to 27 Sep 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
59 sites in 12 countries.
59 sites in 12 countries
Spain9 sites
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Universitario de Gran Canaria Doctor Negrin
Las Palmas, 35010
MD Anderson Cancer Center
Madrid, 28033
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario 12 de Octubre
Madrid
Hospital Universitario Virgen de la Victoria de Málaga
Málaga, 29010
Hospital Universitario de Salamanca
Salamanca, 37007
Hospital Clínico Universitario de Valencia
Valencia, 46010
United States8 sites
University of Maryland Medical Center
Baltimore, Maryland, 21201
University of Chicago
Chicago, Illinois, 60637
The Ohio State University
Columbus, Ohio, 43210
MD Anderson Cancer Center
Houston, Texas, 77030
Mount Sinai
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Weill Cornell
New York, New York, 10065
Oregon Health and Science University
Portland, Oregon, 97239
Australia5 sites
Monash Health
Clayton
St. George Hospital
Kogarah
Royal Perth Hospital
Perth, 6000
Calvary Mater Newcastle Hospital
Waratah, 2298
Perth Blood Institute
West Perth, 6005
Belgium5 sites
Institut Jules Bordet
Anderlecht, 1070
Cliniques universitaires Saint-Luc
Brussels
UZ Gent
Ghent
Centre Hospitalier (CH) Jolimont
Haine-Saint-Paul, 7100
AZ Turnhout
Turnhout
Germany5 sites
Universitätsklinikum Halle
Halle
Universitätsklinikum Hamburg-Eppendorf
Hamburg
University Hospital Jena
Jena, 07747
Universitätsklinikum Leipzig
Leipzig
Universitaetsklinikum Schleswig-Holstein
Lübeck
Israel5 sites
Rambam Health Care Campus
Haifa, 3109601
Hadassah Medical Center Ein Kerem
Jerusalem
The Chaim Sheba Medical Center
Ramat Gan, 5265601
Tel-Aviv Sourasky Medical Center
Tel Aviv, 6423906
Assaf Harofeh Medical Center AHMC
Tel Aviv
Italy5 sites
AOU Policlinico S.Orsola-Malpighi
Bologna
Universitaria Maggiore della Carità Novara
Novara, Piedmont, 28100
A.O.O.R. Villa Sofia Cervello
Palermo, Sicily, 90146
AORMN Hospital Hematology and BMT Center
Pesaro
AOUS Le Scotte
Siena, 53100
France4 sites
Centre Hospitalier Universitaire (CHU) de Bordeaux
Bordeaux, 33000
Institut Paoli Calmettes
Marseille, 13009
Centre Hospitalier Universitaire (CHU) de Nice
Nice, 06000
Hôpital Saint-Louis
Paris
Hungary4 sites
Semmelweis Egyetem
Budapest, 1085
Del-Pesti Centrumkorhaz Orszagos Hematologiai es Infektologi
Budapest
szabolcs-szatmár-bereg megyei kórházak és egyetemi oktatókórház Jósa András Oktatókórház
Debrecen
Somogy Megyei KAposi Mor Oktato Korhaz
Kaposvár, 7400
South Korea4 sites
Inje University Busan Paik Hospital
Busan
Seoul National University Hospital
Seoul, 03080
Samsung Medical Center
Seoul
The Catholic University of Korea-Seoul St. Mary's Hospital
Seoul
United Kingdom4 sites
Birmingham Heartlands Hospital
Birmingham
University Hospital of Wales
Cardiff
The Royal Marsden Hospital
London, SW3 6JJ
Oxford University Hospitals NHS Trust, Churchill Hospital
Oxford
About this study
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).
- Conditions
- Relapsed or Refractory Acute Myeloid Leukemia (AML), Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN)
- Being tested
- KRT-232, Cytarabine, Decitabine
- Keywords
- navtemadlin
- Medical subject headings
- Recurrence, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KRT-232Drug
KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.
CytarabineDrug
Also called cytosine arabinoside, Cytosar-U, Depocyt, Arabinosylcytosine
Cytarabine is an anti-cancer chemotherapy drug taken via injection.
DecitabineDrug
Also called Dacogen
Decitabine is an anti-cancer chemotherapy drug taken via injection.
| Study group | Role | What they receive |
|---|---|---|
| Part A - Arm 1 | Experimental | 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. Receives: Drug: KRT-232; Drug: Cytarabine |
| Part A - Arm 2 | Experimental | 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. Receives: Drug: KRT-232; Drug: Decitabine |
| Part A - Arm 3 | Experimental | 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. Receives: Drug: KRT-232; Drug: Decitabine |
| Part B - Arm 1 | Experimental | KRT-232 administered at 360 mg orally, once daily (QD) on Days 1-7 with 21 days off on a 28-day treatment cycle Receives: Drug: KRT-232 |
| Part B - Arm 2 | Experimental | 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. Receives: Drug: KRT-232 |
| Part B - Arm 3 | Experimental | KRT-232 administered at 180 mg orally, once daily (QD) on Days 1-7 with 14 days off on a 21-day treatment cycle. Receives: Drug: KRT-232 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 28 Days
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
Measured: 2 years after last patient enrolled
Secondary outcomes (2)
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
Measured: 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)
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
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2019
- Study start25 Sep 2019
- Primary completion27 Sep 2023
- Study completion27 Sep 2023
Why it stopped: In September 2023, the study was terminated because of a Sponsor decision, unrelated to safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kartos Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04113616
- Sponsor's protocol ID
- KRT-232-104
- Status last verified
- Mar 2024
- First submitted
- 1 Oct 2019
- Last updated
- 22 Mar 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04113616
- Acronym / sponsor ID
- KRT-232-104
- Conditions
- Relapsed or Refractory Acute Myeloid Leukemia (AML), Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN)
- Keywords
- navtemadlin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: In September 2023, the study was terminated because of a Sponsor decision, unrelated to safety concerns.
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Kartos Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 25 Sep 2019 (actual)
- Primary completion
- 27 Sep 2023 (actual)
- Study completion
- 27 Sep 2023 (actual)
- First posted
- 3 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part A - Arm 1 | Experimental | Drug: KRT-232, Drug: CytarabineKRT-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. |
| Part A - Arm 2 | Experimental | Drug: KRT-232, Drug: DecitabineKRT-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. |
| Part A - Arm 3 | Experimental | Drug: KRT-232, Drug: DecitabineKRT-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. |
| Part B - Arm 1 | Experimental | Drug: KRT-232KRT-232 administered at 360 mg orally, once daily (QD) on Days 1-7 with 21 days off on a 28-day treatment cycle |
| Part B - Arm 2 | Experimental | Drug: KRT-232KRT-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. |
| Part B - Arm 3 | Experimental | Drug: KRT-232KRT-232 administered at 180 mg orally, once daily (QD) on Days 1-7 with 14 days off on a 21-day treatment cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KRT-232KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth. | Drug | Part A - Arm 1, Part A - Arm 2, Part A - Arm 3, Part B - Arm 1, Part B - Arm 2, Part B - Arm 3 |
| CytarabineAlso: cytosine arabinoside, Cytosar-U, Depocyt, ArabinosylcytosineCytarabine is an anti-cancer chemotherapy drug taken via injection. | Drug | Part A - Arm 1 |
| DecitabineAlso: DacogenDecitabine is an anti-cancer chemotherapy drug taken via injection. | Drug | Part A - Arm 2, Part A - Arm 3 |
Primary outcome
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
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 secondary outcomes
Part A: To determine the rates of complete remission (CR) and complete remission with partial hematological improvement (CRh)
Time frame: 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
Results and safety
The study was stopped early (reason given: In September 2023, the study was terminated because of a Sponsor decision, unrelated to safety concerns.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
59 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing KRT-232, Cytarabine and Decitabine in people with Relapsed or Refractory Acute Myeloid Leukemia (AML) and Acute Myeloid Leukemia (AML), Secondary to Myeloproliferative Neoplasms (MPN), run by Kartos Therapeutics, Inc. at 59 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 59 sites in Spain, United States, Australia, Belgium, Germany and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: In September 2023, the study was terminated because of a Sponsor decision, unrelated to safety concerns.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: To determine KRT-232 recommended phase 2 dose (RP2D) (time frame: 28 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2024.