Acute Myeloid LeukemiaPhase 1/2NCT04669067
TL-895 and KRT-232 Study in Acute Myeloid Leukemia
A Phase 1/2 study testing TL-895 and KRT-232 in people with Acute Myeloid Leukemia, run by Telios Pharma, Inc. at 35 sites in 8 countries.
Trial summary
This study evaluates TL-895, a potent, orally available and highly selective irreversible tyrosine kinase inhibitor combined with navtemadlin (KRT-232), a novel oral small molecule inhibitor of MDM2 for the treatment of adults with FLT3 mutated Acute Myeloid Leukemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- TL-895 and KRT-232
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 35 sitesin 8 countries
- Study dates
- 31 Mar 2021to Nov 2025
- 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
- TP53 wildtype AML
- Relapsed/Refractory to at least one prior therapy, one of which must have included a FLT-3 inhibitor
- FLT3 mutation (FLT3-TKD or FLT3-ITD)
- ECOG 0-2
- Adequate hematologic, hepatic, and renal functions
Who cannot join
- AML subtype 3
- Prior treatment with MDM2 antagonist therapies
- Eligible for HSCT
Trial locations and contacts
35 sites in 8 countries.
35 sites in 8 countries
United States11 sites
Georgia Cancer Center
Augusta, Georgia, 30912
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Rush University Medical Center, Division of Hematology Oncology and Cell Therapy
Chicago, Illinois, 60612
University of Cincinnati
Cincinnati, Ohio, 45219
UT Southwestern Medical Center, Harold C. Simmons Cancer Center
Dallas, Texas, 75390
Karmanos Cancer Institute
Detroit, Michigan, 48201
Keck School of Medicine
Los Angeles, California, 90033
Weill Cornell Medical College
New York, New York, 10065
University of California, Irvine Medical Center
Orange, California, 92868
Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
Philadelphia, Pennsylvania, 19107
Seattle Cancer Care Alliance
Seattle, Washington, 98109
France6 sites
Claude Huriez Hospital
Lille, 59037
South Lyon Hospital Center
Lyon, 48178
Paoli-Calmettes Institute
Marseille, 13009
University Hospital of Nantes
Nantes, 44000
Hospital Center Universitaire De Nice
Nice, 06000
Saint-Louis Hospital
Paris, 75010
Germany5 sites
University Duisburg-Essen, University Hospital Essen, Department of Internal Medicine
Essen, 45147
University Hospital Halle (Saale), Department of Internal Medicine IV - Hematology and Oncology
Halle, Saxony-Anhalt, 06120
University Hospital Hamburg-Eppendorf, Department of Internal Medicine II
Hamburg, 20246
Hannover Medical School, Center for Internal Medicine, Clinic of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation
Hanover, 30625
University Hospital Jena, Clinic of Internal Medicine II, Department of Hematology and Medical Oncology
Jena, 07747
Spain4 sites
University Hospital Germans Trias i Pujol, Department of Clinical Hematology
Badalona, 08916
University Hospital Vall d'Hebron
Barcelona, 08035
University Clinical Hospital of Valencia, Department of Hematology and Medical Oncology
Valencia, 46010
Hospital Universitario y Politécnico de La Fe
Valencia, 46026
Italy3 sites
University Hospital - Ospedali Riuniti Umberto I - GM Lancisi - G Salesi of Ancona, Haematology Clinic
Ancona, 60126
Polyclinic S. Orsola-Malpighi, Operative Unit of Hematology
Bologna, 40138
Romagnolo Scientific Institute of Meldola (IRST) S.r.l., Department of Oncology and Clinical and Experimental Haematology
Meldola, 47014
Australia2 sites
University of Sunshine Coast-Sippy Downs
Sippy Downs, 4556
Westmead Hospital
Sydney, 2145
Austria2 sites
Ordensklinikum Linz GmbH Elisabethinen
Linz, 4020
Medical University Vienna, Department of Internal Medicine I, Clinical Department of Hematology and Hemostaseology
Vienna, 1090
South Korea2 sites
Gachon University Gil Medical Center
Incheon, 21565
Seoul National University Hospital, Department of Hemato-Oncology
Seoul, 03080
About this study
Official title: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of TL-895 Combined With KRT-232 in Patients With Relapsed/Refractory (R/R) FLT3+ Acute Myeloid Leukemia (AML)
This study evaluates TL-895, a potent, orally available and highly selective irreversible tyrosine kinase inhibitor combined with navtemadlin (KRT-232), a novel oral small molecule inhibitor of MDM2 for the treatment of adults with FLT3 mutated Acute Myeloid Leukemia. Participants must be relapsed/refractory (e.g., having failed prior therapy) to be eligible for this study.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- TL-895, KRT-232
- Keywords
- AML, TP53, FLT3+, Navtemadlin
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TL-895Drug
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
KRT-232Drug
KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1b - Dose Level 1 | Experimental | KRT-232 240mg QD, orally administered on days 1 through 7 of each 28-day cycle in combination with TL-895 150mg BID continuously for each 28-day cycle. Receives: Drug: TL-895; Drug: KRT-232 |
| Phase 1b - Dose Level 2 | Experimental | KRT-232 300mg QD, orally administered on days 1 through 7 of each 28-day cycle in combination with TL-895 150mg BID continuously for each 28-day cycle. Receives: Drug: TL-895; Drug: KRT-232 |
| Phase 1b - Dose Level 3 | Experimental | Cycle 1 only: KRT-232 360 mg QD orally administered on Days 1 through 7 of the first 28-day cycle in combination with TL-895 150 mg BID continuously for the first 28-day cycle
Cycle 2 and beyond: KRT-232 300 mg QD orally administered on Days 1 through 7 of each 28-day cycle in combination with TL-895 150 mg BID continuously for each 28-day cycle. Receives: Drug: TL-895; Drug: KRT-232 |
| Phase 1b - Dose Level 4 | Experimental | Cycle 1 only: KRT-232 360 mg QD orally administered on Days 1 through 7 of the first 28-day cycle in combination with TL-895 300 mg BID continuously for the first 28-day cycle.
Cycle 2 and beyond: KRT-232 300 mg QD orally administered on Days 1 through 7 of each 28-day cycle in combination with TL-895 300 mg BID continuously for each 28-day cycle. Receives: Drug: TL-895; Drug: KRT-232 |
| Phase 1b - Dose Level 5 | Experimental | Cycle 1 only: KRT-232 360 mg QD orally administered on Days 1 through 7 of the first 28-day cycle in combination with TL-895 450 mg BID continuously for the first 28-day cycle.
Cycle 2 and beyond: KRT-232 300 mg QD orally administered on Days 1 through 7 of each 28-day cycle in combination with TL-895 450 mg BID continuously for each 28-day cycle. Receives: Drug: TL-895; Drug: KRT-232 |
| Phase 2 - Dose Expansion | Experimental | Dose expansion of the recommended phase 2 dose of TL-895 in combination with KRT-232 as determined in Phase 1b. Receives: Drug: TL-895; Drug: KRT-232 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Objective, Phase 1b: To determine the MTD/MAD and recommended Phase 2 dose (RP2D) of TL-895 in combination with KRT-232
Dose limiting toxicities will be used to established the MTD/MAD of TL-895 combined with KRT-232. The Safety Review Committee (SRC) will determine the RP2D based on safety data of the combination of TL-895 and KRT-232.
Measured: 13 months
Primary Objective, Phase 2: To determine the rates of complete remission (CR) and complete remission with partial hematologic recovery (CRh)
The proportion of subjects who achieved CR or CRh as their best response based on the Modified 2017 European LeukemiaNet (ELN) Response Criteria (Appendix 4).
Measured: 41 months
Secondary outcomes (2)
Key Secondary Objective: To determine the overall response rate (ORR)
The proportion of subjects who achieve PR or better.
Measured: 41 months
Key Secondary Objective: To determine the duration of CR/CRh response (DOR)
Median DOR (Kaplan-Meier estimate) defined as the time from first observation of CR/CRh to relapse or death from any cause, whichever occurs first. Subjects with MLFS by bone marrow biopsy performed earlier in the course of therapy who convert to CR or CRh do not require a separate bone marrow aspirate at the time of CR or CRh to document this.
Measured: 41 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2020
- Study start31 Mar 2021
- Primary completionNov 2024 (estimated)
- Study completionNov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute 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
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Telios Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Kartos Therapeutics, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04669067
- Sponsor's protocol ID
- TL-895-203
- Status last verified
- Feb 2023
- First submitted
- 2 Dec 2020
- Last updated
- 17 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2023. 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 TL-895 Combined With KRT-232 in Patients With Relapsed/Refractory (R/R) FLT3+ Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT04669067
- Acronym / sponsor ID
- TL-895-203
- Conditions
- Acute Myeloid Leukemia
- Keywords
- AML, TP53, FLT3+, Navtemadlin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Telios Pharma, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Kartos Therapeutics, Inc.
- Study start
- 31 Mar 2021 (actual)
- Primary completion
- Nov 2024 (estimated)
- Study completion
- Nov 2025 (estimated)
- First posted
- 16 Dec 2020 (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 TL-895, a potent, orally available and highly selective irreversible tyrosine kinase inhibitor combined with navtemadlin (KRT-232), a novel oral small molecule inhibitor of MDM2 for the treatment of adults with FLT3 mutated Acute Myeloid Leukemia. Participants must be relapsed/refractory (e.g., having failed prior therapy) to be eligible for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Phase 1b - Dose Level 1 | Experimental | Drug: TL-895, Drug: KRT-232KRT-232 240mg QD, orally administered on days 1 through 7 of each 28-day cycle in combination with TL-895 150mg BID continuously for each 28-day cycle. |
| Phase 1b - Dose Level 2 | Experimental | Drug: TL-895, Drug: KRT-232KRT-232 300mg QD, orally administered on days 1 through 7 of each 28-day cycle in combination with TL-895 150mg BID continuously for each 28-day cycle. |
| Phase 1b - Dose Level 3 | Experimental | Drug: TL-895, Drug: KRT-232Cycle 1 only: KRT-232 360 mg QD orally administered on Days 1 through 7 of the first 28-day cycle in combination with TL-895 150 mg BID continuously for the first 28-day cycle Cycle 2 and beyond: KRT-232 300 mg QD orally administered on Days 1 through 7 of each 28-day cycle in combination with TL-895 150 mg BID continuously for each 28-day cycle. |
| Phase 1b - Dose Level 4 | Experimental | Drug: TL-895, Drug: KRT-232Cycle 1 only: KRT-232 360 mg QD orally administered on Days 1 through 7 of the first 28-day cycle in combination with TL-895 300 mg BID continuously for the first 28-day cycle. Cycle 2 and beyond: KRT-232 300 mg QD orally administered on Days 1 through 7 of each 28-day cycle in combination with TL-895 300 mg BID continuously for each 28-day cycle. |
| Phase 1b - Dose Level 5 | Experimental | Drug: TL-895, Drug: KRT-232Cycle 1 only: KRT-232 360 mg QD orally administered on Days 1 through 7 of the first 28-day cycle in combination with TL-895 450 mg BID continuously for the first 28-day cycle. Cycle 2 and beyond: KRT-232 300 mg QD orally administered on Days 1 through 7 of each 28-day cycle in combination with TL-895 450 mg BID continuously for each 28-day cycle. |
| Phase 2 - Dose Expansion | Experimental | Drug: TL-895, Drug: KRT-232Dose expansion of the recommended phase 2 dose of TL-895 in combination with KRT-232 as determined in Phase 1b. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- TP53 wildtype AML
- Relapsed/Refractory to at least one prior therapy, one of which must have included a FLT-3 inhibitor
- FLT3 mutation (FLT3-TKD or FLT3-ITD)
- ECOG 0-2
- Adequate hematologic, hepatic, and renal functions
Key exclusion criteria (3 listed)
- AML subtype 3
- Prior treatment with MDM2 antagonist therapies
- Eligible for HSCT
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 |
|---|---|---|
| TL-895TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth. | Drug | Phase 1b - Dose Level 1, Phase 1b - Dose Level 2, Phase 1b - Dose Level 3, Phase 1b - Dose Level 4, Phase 1b - Dose Level 5, Phase 2 - Dose Expansion |
| KRT-232KRT-232 is an experimental MDM2 inhibitor anticancer drug taken by mouth. | Drug | Phase 1b - Dose Level 1, Phase 1b - Dose Level 2, Phase 1b - Dose Level 3, Phase 1b - Dose Level 4, Phase 1b - Dose Level 5, Phase 2 - Dose Expansion |
Primary outcome
Primary Objective, Phase 1b: To determine the MTD/MAD and recommended Phase 2 dose (RP2D) of TL-895 in combination with KRT-232
Time frame: 13 months
Dose limiting toxicities will be used to established the MTD/MAD of TL-895 combined with KRT-232. The Safety Review Committee (SRC) will determine the RP2D based on safety data of the combination of TL-895 and KRT-232.
Primary Objective, Phase 2: To determine the rates of complete remission (CR) and complete remission with partial hematologic recovery (CRh)
Time frame: 41 months
The proportion of subjects who achieved CR or CRh as their best response based on the Modified 2017 European LeukemiaNet (ELN) Response Criteria (Appendix 4).
2 secondary outcomes
Key Secondary Objective: To determine the overall response rate (ORR)
Time frame: 41 months
Key Secondary Objective: To determine the duration of CR/CRh response (DOR)
Time frame: 41 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2023.
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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.
35 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 TL-895 and KRT-232 in people with Acute Myeloid Leukemia, run by Telios Pharma, Inc. at 35 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 5 inclusion and 3 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 17 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, France, Germany, Spain, Italy 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?
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?
Primary Objective, Phase 1b: To determine the MTD/MAD and recommended Phase 2 dose (RP2D) of TL-895 in combination with KRT-232 (time frame: 13 months). 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 17 Feb 2023.