Acute Myeloid LeukemiaPhase 2NCT04905407
Tamibarotene Plus Venetoclax/Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)
A Phase 2 study testing Tamibarotene, Venetoclax and Azacitidine in people with Acute Myeloid Leukemia, run by Syros Pharmaceuticals at 28 sites in 2 countries.
Trial summary
Tamibarotene is being studied as a treatment for participants with a type of leukemia called acute myeloid leukemia, or AML for short. Tamibarotene is being studied as a treatment for participants with AML whose cancer has a specific genetic abnormality characterized by the overexpression of the retinoic acid receptor… 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?
- Tamibarotene, Venetoclax and Azacitidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 28 sitesin 2 countries
- Study dates
- 26 Aug 2021to 12 Aug 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- All participants must have obtained a blood sample for RARA biomarker investigational assay testing prior to starting treatment on Cycle 1 Day 1. The results of the investigational biomarker assay for all participants must be confirmed as RARA-positive by Cycle 1 Day 8 to enroll (Part 1) or to be randomized (Part 2) in the study.
- Participants must have newly diagnosed, previously untreated non-acute promyelocytic leukemia (APL) AML with a bone marrow or peripheral blood blast count ≥20% and must be unlikely to tolerate standard intensive chemotherapy at the time of Cycle 1 Day 1 Visit due to age, performance status, or comorbidities based on at least one of the following criteria:
- age ≥75 years old, or
- age <75 years old, with at least one of the following:
- Eastern Cooperative Oncology Group (ECOG) performance status of 3
- cardiac history of congestive heart failure (CHF) or documented ejection fraction (EF) ≤50%
Show all 10Show fewer
- pulmonary disease with diffusing capacity of the lungs for carbon monoxide (DLCO) ≤65% or forced expiratory volume in one second (FEV1) ≤65%
- creatinine clearance ≥30 milliliters (mL)/minute (min) to <45 mL/min based on the Cockcroft-Gault glomerular filtration rate estimation
- hepatic impairment with total bilirubin >1.5 to ≤3.0 * upper limit of normal (ULN)
- any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy, and reviewed and approved by the sponsor.
Who cannot join
- Participants have APL.
- Participants have known active central nervous system involvement with AML.
- Prior treatment (before Cycle 1 Day 1) for the diagnosis of AML, myelodysplastic syndromes (MDS), or antecedent hematologic malignancy with any hypomethylating agent, venetoclax, chemotherapy, or hematopoietic stem cell transplantation (HSCT), with the exception of prior treatment with hydroxyurea.
Trial locations and contacts
28 sites in 2 countries.
28 sites in 2 countries
United States15 sites
Northside
Atlanta, Georgia, 30342
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263
Novant Health
Charlotte, North Carolina, 28204
The Ohio State University James Cancer Hospital
Columbus, Ohio, 43210
University of Colorado
Denver, Colorado, 80204
Sarah Cannon Research Institute at Colorado Blood Cancer Institute
Denver, Colorado, 80218
City of Hope
Duarte, California, 91010
Hartford HealthCare
Hartford, Connecticut, 06102
University of Mississippi
Jackson, Mississippi, 39213
HCA Midwest Research Medical Center
Kansas City, Missouri, 64132
UCLA Medical Center Division of Hematology/Oncology
Los Angeles, California, 90095
Atlantic Health
Morristown, New Jersey, 07960
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Oregon Health & Science University
Portland, Oregon, 97239
France13 sites
CHU Angers
Angers, 49000
CH de la Côte Basque
Bayonne, 64100
Hôpital Avicenne Hématologie Clinique
Bobigny, 93000
CHU de Caen Normandie
Caen, 14033
CHU Limoges
Limoges
CHU de Nantes - Hôtel Dieu
Nantes
Hôpital l'Archet- CHU de Nice
Nice, 06202
CHU de Bordeaux - Hôpital Haut-Lévèque
Pessac, 33604
CHU Lyon Sud
Pierre-Bénite, Pierre Benite, 69495
CHU de Poitiers
Poitiers, 86021
Hôpital Saint-Louis
Vellefaux, 75475
Centre Hospitalier de Versailles
Versailles, 78150
Institut Gustave Roussy
Villejuif, 94800
About this study
Official title: Tamibarotene in Combination With Venetoclax and Azacitidine in Previously Untreated Adult Patients Selected for RARA-positive AML Who Are Ineligible for Standard Induction Therapy
Tamibarotene is being studied as a treatment for participants with a type of leukemia called acute myeloid leukemia, or AML for short. Tamibarotene is being studied as a treatment for participants with AML whose cancer has a specific genetic abnormality characterized by the overexpression of the retinoic acid receptor alpha (RARA) gene. This genetic profile is found in about 3 of every 10 people with AML.
During the trial, tamibarotene will be given with 2 other drugs that are already used together to treat people who have AML and who cannot start treatment with standard chemotherapy.
Read the detailed description
This study consists of 3 parts. In Part 1, the safety, tolerability, and pharmacokinetic (PK) evaluation of tamibarotene/venetoclax/azacitidine combination will inform the appropriate tamibarotene dose to be combined with the standard of care (SOC) venetoclax/azacitidine in Part 2 and Part 3. In Part 2, participants will be randomized 1:1 to receive either tamibarotene/venetoclax/azacitidine or venetoclax/azacitidine to compare the clinical activity of the 2 combinations. In Part 3, tamibarotene will be added to the venetoclax/azacytidine regimen of a subset of Part 2 participants who experience progressive disease, relapse after initial complete remission (CR) or CR with incomplete blood count recovery (CRi) response, or treatment failure.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Tamibarotene, Venetoclax, Azacitidine
- 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.
TamibaroteneDrug
Tamibarotene tablets will be administered per dose and schedule specified in the arm.
VenetoclaxDrug
Also called Venclexta
Venetoclax tablets will be administered per dose and schedule specified in the arm.
AzacitidineDrug
Also called Vidaza
Azacitidine injection will be administered per dose and schedule specified in the arm.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Tamibarotene/Venetoclax/Azacitidine | Experimental | Participants will receive the tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 milligrams (mg)/square meter (m^2) once daily, on Days 1 through 7 of each 28-day therapy cycle (per VIDAZA USPI). Alternative dosing of azacitidine (Days 1 through 5, 8, and 9) will be permitted throughout the study.
Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing is 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond.
Tamibarotene 6 mg twice daily (BID) orally, on Days 8 through 28 of each 28-day therapy cycle. Tamibarotene will only be administered to participants who have been confirmed as RARA-positive. Receives: Drug: Tamibarotene; Drug: Venetoclax; Drug: Azacitidine |
| Part 2: Tamibarotene/Venetoclax/Azacitidine | Experimental | Participants will receive the tamibarotene/venetoclax/azacitidine triplet combination at the dose and regimen selected in Part 1. Receives: Drug: Tamibarotene; Drug: Venetoclax; Drug: Azacitidine |
| Part 2: Venetoclax/Azacitidine | Active comparator | Participants will receive the venetoclax/azacitidine combination at the dose and regimen selected in Part 1. Receives: Drug: Venetoclax; Drug: Azacitidine |
| Part 3: Tamibarotene/Venetoclax/Azacitidine | Experimental | Part 2 participants treated with venetoclax/azacitidine who experience progressive disease, relapse after initial CR or CRi response, or treatment failure may begin subsequent treatment in Part 3, where tamibarotene will be added to their regimen. Receives: Drug: Tamibarotene; Drug: Venetoclax; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence that developed or worsened in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. A TEAE was any untoward medical occurrence associated with use of a study drug/study participation, whether or not considered related to study drug after first dose. TEAEs were defined as those adverse events AEs with onset after the first dose of study treatment or existing events that worsened after the first dose during the study up until the last dose of study treatment plus 30 days. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
Measured: Up to 3 years
Part 2: Complete Remission/Complete Remission With Incomplete Hematologic Recovery (CR/CRi) Rate
CR/CRi rate was estimated by the percentage of participants who achieved complete Remission (CR) and/or CR with incomplete hematologic recovery (CRi),CR/CRi (as determined by the investigator). CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts <5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.CRi was defined as absolute neutrophil count <1,000/µL, platelets count <100,000/µL, bone marrow blasts <5% and all CR criteria met except either neutrophils or platelets not recovered.
Measured: Up to 3 years
Secondary outcomes (12)
Part 1: Overall Response Rate (ORR)
ORR: percentage of participants who achieved a overall response as comprised of CR(ANC ≥1,000/µL, platelets count (PC) ≥100,000/µL, bone marrow blasts <5% and absence of circulating blasts and blasts with auer rods;absence of extramedullary disease),CRi (ANC <1,000/µL, PC <100,000/µL, bone marrow blasts <5% and all CR criteria met except either neutrophils or platelets not recovered), CRh (ANC >500/µL, PC >500,000/µL, bone marrow blasts <5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts), morphologically leukemia-free state (bone marrow blasts <5%, absence of blasts with auer rods and <5% blasts in marrow sample with a count of at least 200 nucleated cells or cellularity ≥10%. Absence of EMD. No hematologic criteria required.), or PR was defined as ANC <1,000/µL, PC <100,000/µL, ≥50% decrease from baseline, with decrease to 5-25. ORR was calculated as ORR (%)=number of overall responders/number of participants in the Safety Population×100.
Measured: Up to 3 years
Part 1: Plasma Concentration of Tamibarotene
Measured: Day 8 and 22 of Cycle 1, Day 15 of Cycles 2 and 3 (cycle length = 28 days)
Part 2: Number of Participants With Treatment Emergent Adverse Events
An AE was defined as any untoward medical occurrence that developed or worsened in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. A TEAE was any untoward medical occurrence associated with use of a study drug/study participation, whether or not considered related to study drug after first dose. TEAEs were defined as those adverse events AEs with onset after the first dose of study treatment or existing events that worsened after the first dose during the study up until the last dose of study treatment plus 30 days. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
Measured: Up to 3 years
Part 2: Complete Remission (CR) Rate
CR rate was estimated by the percentage of participants who achieved complete remission (as determined by the investigator). CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts <5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.
Measured: Up to 3 years
Part 2: Complete Remission/ Complete Remission With Partial Hematologic Recovery (CR/CRh) Rate
CR/CRh rate was estimated by the percentage of participants who achieved complete Remission (CR) and/or CR with partial hematologic recovery (CRh),CR/CRh (as determined by the investigator). CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts <5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.CRh was defined as absolute neutrophil count >500/µL, platelets count >500,000/µL, bone marrow blasts <5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts.
Measured: Up to 3 years
Part 2: Duration of Complete Remission
Duration of CR was defined as duration from the date of first documented evidence of CR to the date of relapse of disease (as determined by the investigator), or death due to any cause, whichever occurred first. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts <5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.
Measured: Up to 3 years
Part 2: Duration of CR/CRi
Duration of CR/CRi was defined as duration from the date of first documented evidence of CR/CRi to the date of relapse of disease (as determined by the investigator), or death due to any cause, whichever occured first.CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts <5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.CRi was defined as absolute neutrophil count <1,000/µL, platelets count <100,000/µL, bone marrow blasts <5% and all CR criteria met except either neutrophils or platelets not recovered.
Measured: Up to 3 years
Part 2: Duration of CR/CRh
Duration of CR/CRh was defined as duration from the date of first documented evidence of CR/CRh to the date of relapse of disease (as determined by the investigator), or death due to any cause, whichever occured first. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts <5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease. CRh was defined as absolute neutrophil count >500/µL, platelets count >500,000/µL, bone marrow blasts <5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts.
Measured: Up to 3 years
Part 2: Time to Complete Response
Time to CR was defined as the duration from the date of Cycle 1 Day 1 visit to the date of the first documented evidence of CR as determined by the investigator. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts <5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.
Measured: Up to 3 years
Part 2: Time to CR/CRi
Time to CR/CRi was defined as the duration from the date of Cycle 1 Day 1 Visit to the date of the first documented evidence of CR/CRi as determined by the investigator. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts <5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.CRi was defined as absolute neutrophil count <1,000/µL, platelets count <100,000/µL, bone marrow blasts <5% and all CR criteria met except either neutrophils or platelets not recovered.
Measured: Up to 3 years
Part 2: Time to CR/CRh
Time to CR/CRh was defined as the duration from the date of Cycle 1 Day 1 Visit to the date of the first documented evidence of CR/CRh as determined by the investigator. CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts <5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease. CRh was defined as absolute neutrophil count >500/µL, platelets count >500,000/µL, bone marrow blasts <5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts.
Measured: Up to 3 years
Part 2: Overall Response Rate
ORR: percentage of participants who achieved a overall response as comprised of CR(ANC ≥1,000/µL, platelets count (PC) ≥100,000/µL, bone marrow blasts <5% and absence of circulating blasts and blasts with auer rods;absence of extramedullary disease),CRi (ANC <1,000/µL, PC <100,000/µL, bone marrow blasts <5% and all CR criteria met except either neutrophils or platelets not recovered), CRh (ANC >500/µL, PC >500,000/µL, bone marrow blasts <5% and all CR criteria met except ANC and platelets with partial recovery of peripheral counts), morphologically leukemia-free state (bone marrow blasts <5%, absence of blasts with auer rods and <5% blasts in marrow sample with a count of at least 200 nucleated cells or cellularity ≥10%. Absence of EMD. No hematologic criteria required.), or PR was defined as ANC <1,000/µL, PC <100,000/µL, ≥50% decrease from baseline, with decrease to 5-25. ORR was calculated as ORR (%)=number of overall responders/number of participants in the Safety Population×100.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2021
- Study start26 Aug 2021
- Primary completion12 Aug 2024
- Study completion12 Aug 2024
Why it stopped: As per sponsor decision, the study was terminated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Syros Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Kelly Executive Medical Director, MD, Study director, Syros Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04905407
- Sponsor's protocol ID
- SY-1425-202
- Status last verified
- Jan 2025
- First submitted
- 24 May 2021
- Last updated
- 24 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cluzeau T, Borate U, McMahon C, Fenaux P, Heiblig M, Peterlin P, Ball B, Chantepie S, Eghtedar A, Kambhampati S, Solh M, Torregrosa-Diaz J, Braun T, Dugan J, Feld J, Gourin MP, Pigneux A, Robin JB, Schiller G, Stein E, Roth D, Kelly M, Pollyea D, de Botton S. Tamibarotene with venetoclax and azacitidine in RARA+ acute myeloid leukemia: results from the SY-1425-202 study. Blood Neoplasia. 2026 Jul 28;3(4):100279. doi: 10.1016/j.bneo.2026.100279. eCollection 2026 Nov.
PubMed 42761251
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tamibarotene in Combination With Venetoclax and Azacitidine in Previously Untreated Adult Patients Selected for RARA-positive AML Who Are Ineligible for Standard Induction Therapy
- ClinicalTrials.gov ID
- NCT04905407
- Acronym / sponsor ID
- SY-1425-202
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: As per sponsor decision, the study was terminated.
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Syros PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 26 Aug 2021 (actual)
- Primary completion
- 12 Aug 2024 (actual)
- Study completion
- 12 Aug 2024 (actual)
- First posted
- 27 May 2021 (actual)
- Results
- Posted 24 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Tamibarotene is being studied as a treatment for participants with a type of leukemia called acute myeloid leukemia, or AML for short. Tamibarotene is being studied as a treatment for participants with AML whose cancer has a specific genetic abnormality characterized by the overexpression of the retinoic acid receptor alpha (RARA) gene. This genetic profile is found in about 3 of every 10 people with AML.
During the trial, tamibarotene will be given with 2 other drugs that are already used together to treat people who have AML and who cannot start treatment with standard chemotherapy.
Detailed description
This study consists of 3 parts. In Part 1, the safety, tolerability, and pharmacokinetic (PK) evaluation of tamibarotene/venetoclax/azacitidine combination will inform the appropriate tamibarotene dose to be combined with the standard of care (SOC) venetoclax/azacitidine in Part 2 and Part 3. In Part 2, participants will be randomized 1:1 to receive either tamibarotene/venetoclax/azacitidine or venetoclax/azacitidine to compare the clinical activity of the 2 combinations. In Part 3, tamibarotene will be added to the venetoclax/azacytidine regimen of a subset of Part 2 participants who experience progressive disease, relapse after initial complete remission (CR) or CR with incomplete blood count recovery (CRi) response, or treatment failure.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1: Tamibarotene/Venetoclax/Azacitidine | Experimental | Drug: Tamibarotene, Drug: Venetoclax, Drug: AzacitidineParticipants will receive the tamibarotene/venetoclax/azacitidine triplet combination as follows: Azacitidine (intravenously or subcutaneously) at 75 milligrams (mg)/square meter (m^2) once daily, on Days 1 through 7 of each 28-day therapy cycle (per VIDAZA USPI). Alternative dosing of azacitidine (Days 1 through 5, 8, and 9) will be permitted throughout the study. Venetoclax (orally) daily on Days 1 through 28 per standard of care. Standard of care daily dosing is 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Day 3 and beyond. Tamibarotene 6 mg twice daily (BID) orally, on Days 8 through 28 of each 28-day therapy cycle. Tamibarotene will only be administered to participants who have been confirmed as RARA-positive. |
| Part 2: Tamibarotene/Venetoclax/Azacitidine | Experimental | Drug: Tamibarotene, Drug: Venetoclax, Drug: AzacitidineParticipants will receive the tamibarotene/venetoclax/azacitidine triplet combination at the dose and regimen selected in Part 1. |
| Part 2: Venetoclax/Azacitidine | Active comparator | Drug: Venetoclax, Drug: AzacitidineParticipants will receive the venetoclax/azacitidine combination at the dose and regimen selected in Part 1. |
| Part 3: Tamibarotene/Venetoclax/Azacitidine | Experimental | Drug: Tamibarotene, Drug: Venetoclax, Drug: AzacitidinePart 2 participants treated with venetoclax/azacitidine who experience progressive disease, relapse after initial CR or CRi response, or treatment failure may begin subsequent treatment in Part 3, where tamibarotene will be added to their regimen. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- All participants must have obtained a blood sample for RARA biomarker investigational assay testing prior to starting treatment on Cycle 1 Day 1. The results of the investigational biomarker assay for all participants must be confirmed as RARA-positive by Cycle 1 Day 8 to enroll (Part 1) or to be randomized (Part 2) in the study.
- Participants must have newly diagnosed, previously untreated non-acute promyelocytic leukemia (APL) AML with a bone marrow or peripheral blood blast count ≥20% and must be unlikely to tolerate standard intensive chemotherapy at the time of Cycle 1 Day 1 Visit due to age, performance status, or comorbidities based on at least one of the following criteria:
Key exclusion criteria (3 listed)
- Participants have APL.
- Participants have known active central nervous system involvement with AML.
- Prior treatment (before Cycle 1 Day 1) for the diagnosis of AML, myelodysplastic syndromes (MDS), or antecedent hematologic malignancy with any hypomethylating agent, venetoclax, chemotherapy, or hematopoietic stem cell transplantation (HSCT), with the exception of prior treatment with hydroxyurea.
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 |
|---|---|---|
| TamibaroteneTamibarotene tablets will be administered per dose and schedule specified in the arm. | Drug | Part 1: Tamibarotene/Venetoclax/Azacitidine, Part 2: Tamibarotene/Venetoclax/Azacitidine, Part 3: Tamibarotene/Venetoclax/Azacitidine |
| VenetoclaxAlso: VenclextaVenetoclax tablets will be administered per dose and schedule specified in the arm. | Drug | Part 1: Tamibarotene/Venetoclax/Azacitidine, Part 2: Tamibarotene/Venetoclax/Azacitidine, Part 2: Venetoclax/Azacitidine, Part 3: Tamibarotene/Venetoclax/Azacitidine |
| AzacitidineAlso: VidazaAzacitidine injection will be administered per dose and schedule specified in the arm. | Drug | Part 1: Tamibarotene/Venetoclax/Azacitidine, Part 2: Tamibarotene/Venetoclax/Azacitidine, Part 2: Venetoclax/Azacitidine, Part 3: Tamibarotene/Venetoclax/Azacitidine |
Primary outcome
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to 3 years
An adverse event (AE) was defined as any untoward medical occurrence that developed or worsened in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. A TEAE was any untoward medical occurrence associated with use of a study drug/study participation, whether or not considered related to study drug after first dose. TEAEs were defined as those adverse events AEs with onset after the first dose of study treatment or existing events that worsened after the first dose during the study up until the last dose of study treatment plus 30 days. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
Part 2: Complete Remission/Complete Remission With Incomplete Hematologic Recovery (CR/CRi) Rate
Time frame: Up to 3 years
CR/CRi rate was estimated by the percentage of participants who achieved complete Remission (CR) and/or CR with incomplete hematologic recovery (CRi),CR/CRi (as determined by the investigator). CR was defined as absolute neutrophil count ≥1,000/µL, platelets count ≥100,000/µL, bone marrow blasts <5% and absence of circulating blasts and blasts with auer rods; absence of extramedullary disease.CRi was defined as absolute neutrophil count <1,000/µL, platelets count <100,000/µL, bone marrow blasts <5% and all CR criteria met except either neutrophils or platelets not recovered.
12 secondary outcomes
Part 1: Overall Response Rate (ORR)
Time frame: Up to 3 years
Part 1: Plasma Concentration of Tamibarotene
Time frame: Day 8 and 22 of Cycle 1, Day 15 of Cycles 2 and 3 (cycle length = 28 days)
Part 2: Number of Participants With Treatment Emergent Adverse Events
Time frame: Up to 3 years
Part 2: Complete Remission (CR) Rate
Time frame: Up to 3 years
Part 2: Complete Remission/ Complete Remission With Partial Hematologic Recovery (CR/CRh) Rate
Time frame: Up to 3 years
Part 2: Duration of Complete Remission
Time frame: Up to 3 years
Part 2: Duration of CR/CRi
Time frame: Up to 3 years
Part 2: Duration of CR/CRh
Time frame: Up to 3 years
Part 2: Time to Complete Response
Time frame: Up to 3 years
Part 2: Time to CR/CRi
Time frame: Up to 3 years
Part 2: Time to CR/CRh
Time frame: Up to 3 years
Part 2: Overall Response Rate
Time frame: Up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42761251Cluzeau T, Borate U, McMahon C, Fenaux P, Heiblig M, Peterlin P, Ball B, Chantepie S, Eghtedar A, Kambhampati S, Solh M, Torregrosa-Diaz J, Braun T, Dugan J, Feld J, Gourin MP, Pigneux A, Robin JB, Schiller G, Stein E, Roth D, Kelly M, Pollyea D, de Botton S. Tamibarotene with venetoclax and azacitidine in RARA+ acute myeloid leukemia: results from the SY-1425-202 study. Blood Neoplasia. 2026 Jul 28;3(4):100279. doi: 10.1016/j.bneo.2026.100279. eCollection 2026 Nov.
- Individual participant dataSharing planned: No
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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.
Michael Kelly Executive Medical Director, MD study director
Syros Pharmaceuticals
28 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tamibarotene, Venetoclax and Azacitidine in people with Acute Myeloid Leukemia, run by Syros Pharmaceuticals at 28 sites in 2 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 10 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: stopped early, as of the sponsor's last update on 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, France. 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 24 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) (time frame: Up to 3 years). 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?
On the ClinicalTrials.gov record for NCT04905407, which also lists 1 linked publication.
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 24 Feb 2025.