Myelodysplastic SyndromesPhase 2NCT04906031
Sodium Stibogluconate in the MDS/AML With One of the 65 Defined p53 Mutations
A Phase 2 study testing Sodium stibogluconate in people with Myelodysplastic Syndromes and Acute Myeloid Leukemia, run by First Affiliated Hospital of Jinan University at 1 site in China.
Trial summary
To evaluate the safety and effectiveness of Sodium Stibogluconate in the treatment of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) with p53 mutation from a defined list. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Myelodysplastic Syndromes, Acute Myeloid Leukemia, Myeloid Malignancy
- What is being tested?
- Sodium stibogluconate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2020to 1 Feb 2024
- Phase
- Phase 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically confirmed myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
- Patients with one of the 65 antimonial-treatable p53 mutations with > 5% VAF: Q136P, Y234H, V272M, F270V, P278A, R213L, Y126H, T253N, T253I, R158L, Q136E, P142F, A129D, L194R, R110P, V172G, C176F, I254N, K305R, E285D, T155P, H296D, E258G, G279V, T211A, R213P, C229Y, I232F, E294K, P152R, R196P, M160T, N131S, N131H, K139N, L330H, Y220N, E298Q, D148E, L264R, E224D, H168P, N263H, K320N, S227C, E286D, K292T, V203A, M237R, F212L, K132Q, Y236S, Y126S, Q136H, E221A, I232S, Y163H, P190T, C182Y, P142L, Y163S, V218E, I195S, V272A, and S106R.
- Life expectancy >12 weeks.
- ECOG Performance status < 3.
- Aged from 18 to 75.
- Active bone marrow hyperplasia indicated by morphology.
Show all 10Show fewer
- Normal liver and renal function, bilirubin ≤35μmol/L, ASL/ALT lower than 2xULN, creatinine level ≤150μmol/L.
- Normal cardiac function.
- Lung function: dyspnea ≤ CTC AE grade 1 and SaO2≥ 92% in indoor air environment.
- Written Informed consent.
Who cannot join
- Confirmed CNS involvement.
- Severe cardiac diseases including myocardial infarction or heart insufficiency.
- QT interval ≥450ms on ECG.
- With other visceral malignancy.
- Active tuberculosis or HIV(+).
- Patients with pregnancy or lactation.
Show all 13Show fewer
- Allergic or significantly contraindicated to any drugs involved in intervention.
- Previous intolerance or allergy history to similar drugs.
- Participation at same time in another study in which investigational drugs are used.
- Any other conditions interfering the study.
- Abnormal liver function which does not meet the inclusion criteria.
- ECOG performance status ≥3, CCI >1, ADL <100.
- Aged <18 years or >75years
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
First Affiliated Hospital of Jinan University
Guangzhou, Guangdong, 510632
Hui Zeng, MD
About this study
Official title: Sodium Stibogluconate in the Myelodysplastic Syndromes/Acute Myeloid Leukemia With One of the 65 Defined p53 Mutations That Can be Functionally Rescued by Sodium Stibogluconate
To evaluate the safety and effectiveness of Sodium Stibogluconate in the treatment of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) with p53 mutation from a defined list. The list includes 65 p53 mutations that were experimentally confirmed to be pharmacologically restored with tumor-suppressive function by antimonials.
Read the detailed description
p53 is inactivated by over hundreds of diverse mutations in cancer. The investigator purposefully selected the phenotype-reversible temperature-sensitive (TS) p53 mutations for pharmacological rescue, and pertinently used p53 thermostability as readout to screen for TS p53 mutation rescue compounds. By this, the investigator identified antiparasitic drug antimonials efficiently thermostabilized the TS mutants by noncovalent binding. The antimonials met the three go-to criteria as a targeted drug-availability of co-crystal structure, structure model-compatible Structure-Activity Relationship, and target (p53)-specificity in cells, and consequently extended survival of xenograft mouse with TS p53 mutant.
Under the clinical antiparasitic dosage, the antimonials effectively rescued TS p53 mutant in patient-derived primary acute myeloid leukemia cells. Scan of the most frequent 815 p53 missense mutations identified 65 of them, predominantly TS mutations, as the antimonial-treatable mutations. Thus, the trial aims to evaluate the safety and effectiveness of the approved antimonial-Sodium Stibogluconate-in the treatment of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) with the 65 antimonial-treatable p53 mutants.
- Conditions
- Myelodysplastic Syndromes, Acute Myeloid Leukemia, Myeloid Malignancy, Temperature-Sensitive p53 Mutation, Sodium Stibogluconate, P53 Mutation
- Being tested
- Sodium stibogluconate
- Keywords
- Myelodysplastic Syndromes, Acute Myeloid Leukemia, Myeloid Malignancy, Temperature-sensitive p53 Mutations, Sodium Stibogluconate, p53, precision medicine, antimonial
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium stibogluconateDrug
Also called SSG
Sodium stibogluconate 900 mg/m2/day will be given on d1-5 and d15-19. 28 days per cycle.
| Study group | Role | What they receive |
|---|---|---|
| Sodium stibogluconate | Experimental | Sodium stibogluconate 900 mg/m2/day will be given on d1-5 and d15-19. 28 days per cycle. Receives: Drug: Sodium stibogluconate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
Partial response (PR) + complete response (CR) rate
Measured: At the end of Cycle 4 (each cycle is 28 days)
Secondary outcomes (1)
Adverse Event (AE)
Adverse events (AEs) will be reported and graded
Measured: At the end of Cycle 4 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2021
- Study start1 Jun 2020
- Primary completion1 Feb 2023 (estimated)
- Study completion1 Feb 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromesStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Jinan University
- Sponsor type
- University, hospital or other
- Collaborators
- Ruijin Hospital
- Responsible party
- Principal investigator, Hui Zeng, First Affiliated Hospital of Jinan University
- Investigators
- Min Lu, PHD, Principal investigator, Ruijin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04906031
- Sponsor's protocol ID
- FirstJinanU_SSG
- Status last verified
- Jun 2021
- First submitted
- 18 May 2021
- Last updated
- 9 Jun 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Tang Y, Song H, Wang Z, Xiao S, Xiang X, Zhan H, Wu L, Wu J, Xing Y, Tan Y, Liang Y, Yan N, Li Y, Li J, Wu J, Zheng D, Jia Y, Chen Z, Li Y, Zhang Q, Zhang J, Zeng H, Tao W, Liu F, Wu Y, Lu M. Repurposing antiparasitic antimonials to noncovalently rescue temperature-sensitive p53 mutations. Cell Rep. 2022 Apr 12;39(2):110622. doi: 10.1016/j.celrep.2022.110622.
PubMed 35417717
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sodium Stibogluconate in the Myelodysplastic Syndromes/Acute Myeloid Leukemia With One of the 65 Defined p53 Mutations That Can be Functionally Rescued by Sodium Stibogluconate
- ClinicalTrials.gov ID
- NCT04906031
- Acronym / sponsor ID
- FirstJinanU_SSG
- Conditions
- Myelodysplastic Syndromes, Acute Myeloid Leukemia, Myeloid Malignancy, Temperature-Sensitive p53 Mutation, Sodium Stibogluconate, P53 Mutation
- Keywords
- Myelodysplastic Syndromes, Acute Myeloid Leukemia, Myeloid Malignancy, Temperature-sensitive p53 Mutations, Sodium Stibogluconate, p53, precision medicine, antimonial
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Jinan UniversityUniversity, hospital or other
- Collaborators
- Ruijin Hospital
- Study start
- 1 Jun 2020 (actual)
- Primary completion
- 1 Feb 2023 (estimated)
- Study completion
- 1 Feb 2024 (estimated)
- First posted
- 28 May 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.
To evaluate the safety and effectiveness of Sodium Stibogluconate in the treatment of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) with p53 mutation from a defined list. The list includes 65 p53 mutations that were experimentally confirmed to be pharmacologically restored with tumor-suppressive function by antimonials.
Detailed description
p53 is inactivated by over hundreds of diverse mutations in cancer. The investigator purposefully selected the phenotype-reversible temperature-sensitive (TS) p53 mutations for pharmacological rescue, and pertinently used p53 thermostability as readout to screen for TS p53 mutation rescue compounds. By this, the investigator identified antiparasitic drug antimonials efficiently thermostabilized the TS mutants by noncovalent binding. The antimonials met the three go-to criteria as a targeted drug-availability of co-crystal structure, structure model-compatible Structure-Activity Relationship, and target (p53)-specificity in cells, and consequently extended survival of xenograft mouse with TS p53 mutant.
Under the clinical antiparasitic dosage, the antimonials effectively rescued TS p53 mutant in patient-derived primary acute myeloid leukemia cells. Scan of the most frequent 815 p53 missense mutations identified 65 of them, predominantly TS mutations, as the antimonial-treatable mutations. Thus, the trial aims to evaluate the safety and effectiveness of the approved antimonial-Sodium Stibogluconate-in the treatment of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) with the 65 antimonial-treatable p53 mutants.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sodium stibogluconate | Experimental | Drug: Sodium stibogluconateSodium stibogluconate 900 mg/m2/day will be given on d1-5 and d15-19. 28 days per cycle. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Pathologically confirmed myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
- Patients with one of the 65 antimonial-treatable p53 mutations with > 5% VAF: Q136P, Y234H, V272M, F270V, P278A, R213L, Y126H, T253N, T253I, R158L, Q136E, P142F, A129D, L194R, R110P, V172G, C176F, I254N, K305R, E285D, T155P, H296D, E258G, G279V, T211A, R213P, C229Y, I232F, E294K, P152R, R196P, M160T, N131S, N131H, K139N, L330H, Y220N, E298Q, D148E, L264R, E224D, H168P, N263H, K320N, S227C, E286D, K292T, V203A, M237R, F212L, K132Q, Y236S, Y126S, Q136H, E221A, I232S, Y163H, P190T, C182Y, P142L, Y163S, V218E, I195S, V272A, and S106R.
- Life expectancy >12 weeks.
- ECOG Performance status < 3.
- Aged from 18 to 75.
Key exclusion criteria (13 listed)
- Confirmed CNS involvement.
- Severe cardiac diseases including myocardial infarction or heart insufficiency.
- QT interval ≥450ms on ECG.
- With other visceral malignancy.
- Active tuberculosis or HIV(+).
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 |
|---|---|---|
| Sodium stibogluconateAlso: SSGSodium stibogluconate 900 mg/m2/day will be given on d1-5 and d15-19. 28 days per cycle. | Drug | Sodium stibogluconate |
Primary outcome
Overall response rate
Time frame: At the end of Cycle 4 (each cycle is 28 days)
Partial response (PR) + complete response (CR) rate
1 secondary outcome
Adverse Event (AE)
Time frame: At the end of Cycle 4 (each cycle is 28 days)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2021.
- Derived from this study: PubMed 35417717Tang Y, Song H, Wang Z, Xiao S, Xiang X, Zhan H, Wu L, Wu J, Xing Y, Tan Y, Liang Y, Yan N, Li Y, Li J, Wu J, Zheng D, Jia Y, Chen Z, Li Y, Zhang Q, Zhang J, Zeng H, Tao W, Liu F, Wu Y, Lu M. Repurposing antiparasitic antimonials to noncovalently rescue temperature-sensitive p53 mutations. Cell Rep. 2022 Apr 12;39(2):110622. doi: 10.1016/j.celrep.2022.110622.
- Individual participant dataSharing planned: Undecided
Related trials for Myelodysplastic Syndromes
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
High Grade Myelodysplastic Syndromes
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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.
Min Lu, PHD principal investigator
Ruijin Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sodium stibogluconate in people with Myelodysplastic Syndromes and Acute Myeloid Leukemia, run by First Affiliated Hospital of Jinan University at 1 site in China.
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 13 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 9 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hui Zeng, MD (+86 18002201919, androps2011@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (time frame: At the end of Cycle 4 (each cycle is 28 days)). 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 NCT04906031, 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 9 Jun 2021.