Chronic Myeloid LeukemiaPhase 1/2NCT04835584
KRT-232 and TKI Study in Chronic Myeloid Leukemia
A Phase 1/2 study testing KRT-232, Dasatinib and Nilotinib in people with Chronic Myeloid Leukemia, run by Kartos Therapeutics, Inc. at 26 sites in 8 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- KRT-232, Dasatinib and Nilotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 109 participants
- Where
- 26 sitesin 8 countries
- Study dates
- 7 May 2021to 30 Jun 2026
- 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
- 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
Who cannot join
- 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.
Trial locations and contacts
26 sites in 8 countries.
26 sites in 8 countries
United States5 sites, 5 recruiting
- Recruiting
Georgia Cancer Center at Augusta University
Augusta, Georgia, 30912
- Recruiting
University of Alabama Birmingham
Birmingham, Alabama, 35294
- Recruiting
Texas Oncology- Sammons CC at Baylor
Dallas, Texas, 75246
- Recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
- Recruiting
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
France4 sites, 4 recruiting
- Recruiting
Centre Leon Berard
Lyon, 69008
- Recruiting
APHM Hopital de la Timone
Marseille, 13005
- Recruiting
Institut Paoli-Calmettes
Marseille, 13009
- Recruiting
Centre Hospitalier Lyon Sud
Saint-Genis-Laval, 69310
Italy4 sites, 4 recruiting
- Recruiting
Azienda Ospedaliero - Universitaria Mater Domini
Catanzaro, 88100
- Recruiting
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
Meldola FC, 47014
- Recruiting
Policlinico di Milano Ospedale Maggiore | Fondazione IRCCS Ca' Granda
Milan, MI, 20122
- Recruiting
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
South Korea4 sites, 4 recruiting
- Recruiting
Kyungpook National University Hospital
Daegu
- Recruiting
Samsung Medical Center
Seoul, 135-710
- Recruiting
Seoul National University Hospital
Seoul
- Recruiting
Severance Hospital
Seoul
Spain4 sites, 4 recruiting
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, 08035
- Recruiting
Clínica Universidad de Navarra
Madrid, Navarre, 28027
- Recruiting
Hospital Universitario La Paz
Madrid, 28046
- Recruiting
Clinica Universidad de Navarra
Pamplona, Navarre, 31008
Russia3 sites, 3 recruiting
- Recruiting
National Medical Research Center of Hematology
Moscow, 125167
- Recruiting
Almazov National Medical Research Center
Saint Petersburg, 197341
- Recruiting
Samara State Medical University
Samara, 443001
Canada1 site, 1 recruiting
- Recruiting
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2C1
Poland1 site, 1 recruiting
- Recruiting
Pratia Onkologia Katowice
Katowice, 40-519
About this study
Official title: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With a Tyrosine Kinase Inhibitor (TKI) in Patients With Relapsed or Refractory Ph+ Chronic Myeloid Leukemia (CML)
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
- Being tested
- KRT-232, Dasatinib, Nilotinib
- Keywords
- navtemadlin
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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 anticancer drug taken by mouth.
DasatinibDrug
Also called Dasatinib Zentiva
Dasatinib is a Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
NilotinibDrug
Also called Tasigna
Nilotinib is an Tyrosine Kinase Inhibitor anticancer drug taken by mouth.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: KRT-232; Drug: Dasatinib; Drug: Nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 6 months
Part 2, Arm C: Major hematological response (MaHR) rate
The proportion of subjects who achieved MaHR according to modified ELN criteria
Measured: 6 months
Secondary outcomes (6)
CCyR rate
The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arms A and B
Measured: 12 months
MCyR rate
The proportion of subjects who achieved CCyR or PCyR according to modified ELN criteria in Arm C
Measured: 47 months
Duration of response
DOR (Kaplan-Meier estimate) defined as the time from first observation of response to progression/relapse or death, whichever comes first
Measured: 47 months
Rate of complete hematologic response (CHR)
The proportion of subjects who achieve a CHR according to modified ELN criteria in Arms A and B
Measured: 47 months
Progression-free survival (PFS) in each Arm
PFS is defined as the time from the first treatment dose date to progression/relapse or death, whichever comes first
Measured: 47 months
Overall survival (OS) in each Arm
OS is defined as the time from the first treatment dose date to death from any cause
Measured: 47 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2021
- Study start7 May 2021
- Primary completion31 Dec 2024 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloid LeukemiaStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 109 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kartos Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04835584
- Sponsor's protocol ID
- KRT-232-117
- Status last verified
- Mar 2022
- First submitted
- 5 Apr 2021
- Last updated
- 21 Mar 2022
- 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 21 Mar 2022. 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 Combined With a Tyrosine Kinase Inhibitor (TKI) in Patients With Relapsed or Refractory Ph+ Chronic Myeloid Leukemia (CML)
- ClinicalTrials.gov ID
- NCT04835584
- Acronym / sponsor ID
- KRT-232-117
- Conditions
- Chronic Myeloid Leukemia
- Keywords
- navtemadlin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 109 participants (estimated)
- Lead sponsor
- Kartos Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 7 May 2021 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 8 Apr 2021 (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, 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1, KRT-232 combined with TKI (Dasatinib or Nilotinib) in patients with CML-CP | Experimental | Drug: KRT-232, Drug: Dasatinib, Drug: NilotinibKRT-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. |
| Part 2, Arm A (KRT-232 combined with Dasatinib in patients with CML-CP) | Experimental | Drug: KRT-232, Drug: DasatinibKRT-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. |
| Part 2, Arm B (KRT-232 combined with Nilotinib in patients with CML-CP) | Experimental | Drug: KRT-232, Drug: NilotinibKRT-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. |
| Part 2, Arm C (KRT-232 combined with Dasatinib or Nilotinib in patients with CML-AP) | Experimental | Drug: KRT-232, Drug: Dasatinib, Drug: NilotinibKRT-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
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 anticancer drug taken by mouth. | Drug | 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) |
| DasatinibAlso: Dasatinib ZentivaDasatinib is a Tyrosine Kinase Inhibitor anticancer drug taken by mouth. | Drug | 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) |
| NilotinibAlso: TasignaNilotinib is an Tyrosine Kinase Inhibitor anticancer drug taken by mouth. | Drug | 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) |
Primary outcome
Part 1: Maximum tolerated dose (MTD)/maximum administered dose (MAD) of KRT-232
Time frame: 28 Days
DLTs will be used to establish the MTD/MAD of KRT-232 in combination with dasatinib or nilotinib
Part 2, Arm A and B: Major molecular response (MMR) rate
Time frame: 6 months
The proportion of subjects who achieved complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR) according to modified ELN criteria
Part 2, Arm C: Major hematological response (MaHR) rate
Time frame: 6 months
The proportion of subjects who achieved MaHR according to modified ELN criteria
6 secondary outcomes
CCyR rate
Time frame: 12 months
MCyR rate
Time frame: 47 months
Duration of response
Time frame: 47 months
Rate of complete hematologic response (CHR)
Time frame: 47 months
Progression-free survival (PFS) in each Arm
Time frame: 47 months
Overall survival (OS) in each Arm
Time frame: 47 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2022.
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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.
26 sites in 8 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, Dasatinib and Nilotinib in people with Chronic Myeloid Leukemia, run by Kartos Therapeutics, Inc. at 26 sites in 8 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 6 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 21 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, France, Italy, South Korea, Spain and 3 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact John Mei (650-542-0136, jmei@kartosthera.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Maximum tolerated dose (MTD)/maximum administered dose (MAD) of KRT-232 (time frame: 28 Days). The study lists 3 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 21 Mar 2022.