Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Decitabine

Arsenic Trioxide

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Enzyme Inhibitors

Patients with p53 mutations will be treated with Decitabine,Arsenic Trioxide and Cytarabine.

20mg/m\^2,d1-5,ivgtt,28days as a duration

0.16mg/kg,d1-5,ivgtt,28days as a duration

Li Junmin, MD

Sujiang Zhang, MD

Junmin Li

Junming Li

Min Lu, Ph.D.

Zhang Sujiang

Lu Min

This is a prospective,uncontrolled and multi-institution trial.The aim is to identify if using decitabine,cytarabine and ATO as the therapy of acute myeloid leukemia(AML) with p53 mutations has better relapse free survival and complete response than using decitabine and cytarabine.

TP53 mutation is commonly associated with poor cancer patient prognosis yet no mutant p53 (mp53)-targeting regimen was clinically established. Particularly, p53 mutation is associated with extremely poor prognosis in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients.

Decitabine (DAC) is a FDA approved drug for MDS treatment. In two independent clinical trials reported recently, DNA demethylating drug DAC treatment yielded a surprisingly high rate of complete remission (CR) in mp53-harboring AML/MDS patients (Welch, NEJM, 2016; Chang, BJH, 2017). Notably, all of the mp53-expressing patients in the two clinical studies relapsed quickly.

Arsenic trioxide (ATO) is a FDA approved drug for M3-AML treatment. Despite of the observed efficacy in treating non-APL patients, ATO is not yet approved for non-APL cancer treatment. ATO plays key role in regulating both wild-type p53 (wtp53) and mp53. Our published and unpublished data suggest ATO potentially hijacks nuclear iASPP-mediated STRaND pathway via exposing iASPP's RaDAR nuclear import code (Lu, Cancer Cell, 2013; Lu, Cell, 2014; Lu, Nat Rev Mol Cell Biol, 2016; Lu, unpublished). Our unpublished data also suggests a key role of ATO in regulating mp53 (Lu, The 17th International p53 Workshop, 2017). ATO is widely reported to be able to degrade and thus inhibit mp53's oncogenic function (Hamadeh, BBRC, 1999)(Liu, Blood, 2003). ATO suppressed cancer cell growth by targeting mp53 for degradation by Pirh2 degradation pathway (Yang, JBC, 2011; Yan, PLOS one, 2014);

Here we explore the potential of combination of DAC and ATO in improving the mp53-harboring AML/MDS patients' relapse free survival (RFS) and the ability to thoroughly eliminate mp53 subclone. Basic researches aiming to explore the mechanisms how mp53 cells responds to DAC and/or ATO treatment and how mp53 cells develop resistance to DAC and/or ATO will be coupled. We designate trials aiming for a better treatment regimen for mp53 patients as 'PANDA-Trials'.

This study is designed as a model of precision medicine. About 1500 AML patients will be applied for TP53 sequencing. The bone marrow samples will be collected and its p53 status will be Sanger sequenced in 3-5 days before drug administration. The 100 mp53-positive patients will be trialed, while the others (mp53-negative patients) will be subjected to standard treatment or other clinical trials.

In this study,100 patients with p53 mutations will be enrolled,including newly diagnosed AML aged 60-75,AML transferred from Myelodysplastic Syndrome(MDS) and therapy related AML.

Decitabine,Cytarabine and Arsenic Trioxide for Acute Myeloid Leukemia With p53 Mutations

Decitabine,Cytarabine(Ara-C) and Arsenic Trioxide(ATO) in the Treatment of Acute Myeloid Leukemia With p53 Mutations

since a patient first being determined as complete release until relapse

the percent of patients with complete release in all patients enrolled

from first diagnosed to death whichever the cause is

Li Junmin

director of the hematology department

Symptoms and General Pathology

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Precancerous Conditions

MDS patients of the experimental group will be treated with decitabine and arsenic trioxide.

MDS patients of the controlled group will be treated with decitabine alone.

This is a prospective,controlled and multi-institution trial.The aim is to identify if using decitabine and Arsenic Trioxide(ATO) as the therapy of Myelodysplastic Syndrome(MDS) has better relapse free survival and complete response than using decitabine alone.

TP53 mutation is commonly associated with poor cancer patient prognosis yet no mutant p53 (mp53)-targeting regimen was clinically established. Particularly, p53 mutation is associated with extremely poor prognosis in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients.

Decitabine (DAC) is a FDA approved drug for MDS treatment. In two independent clinical trials reported recently, DNA demethylating drug DAC treatment yielded a surprisingly high rate of complete remission (CR) in mp53-harboring AML/MDS patients (Welch, NEJM, 2016; Chang, BJH, 2017). Notably, all of the mp53-expressing patients in the two clinical studies relapsed quickly.

Arsenic trioxide (ATO) is a FDA approved drug for M3-AML treatment. Despite of the observed efficacy in treating non-APL patients, ATO is not yet approved for non-APL cancer treatment. ATO plays key role in regulating both wild-type p53 (wtp53) and mp53. Our published and unpublished data suggest ATO potentially hijacks nuclear iASPP-mediated STRaND pathway via exposing iASPP's RaDAR nuclear import code (Lu, Cancer Cell, 2013; Lu, Cell, 2014; Lu, Nat Rev Mol Cell Biol, 2016; Lu, unpublished). Our unpublished data also suggests a key role of ATO in regulating mp53 (Lu, The 17th International p53 Workshop, 2017). ATO is widely reported to be able to degrade and thus inhibit mp53's oncogenic function (Hamadeh, BBRC, 1999)(Liu, Blood, 2003). ATO suppressed cancer cell growth by targeting mp53 for degradation by Pirh2 degradation pathway (Yang, JBC, 2011; Yan, PLOS one, 2014);

Here we explore the potential of combination of DAC and ATO in improving the mp53-harboring AML/MDS patients' relapse free survival (RFS) and the ability to thoroughly eliminate mp53 subclone. Basic researches aiming to explore the mechanisms how mp53 cells responds to DAC and/or ATO treatment and how mp53 cells develop resistance to DAC and/or ATO will be coupled. We designate trials aiming for a better treatment regimen for mp53 patients as 'PANDA-Trials'.

300 MDS patients will be recruited for trial. They will be randomly administrated with ATO + decitabine (n=200) or decitabine alone (n=100). The RSF, CR ratio, overall survival will be compared between the two arms. Importantly, TP53 status will be sequenced and its correlation with RSF, CR ratio, overall survival within the two arms will be investigated.

Decitabine and Arsenic Trioxide for Myelodysplastic Syndrome(MDS)

Decitabine and Arsenic Trioxide(ATO) in the Treatment of Myelodysplasic Syndrome

Immune System Diseases

Hypersensitivity

Antimony Sodium Gluconate

Antiprotozoal Agents

Antiparasitic Agents

Anthelmintics

Sodium stibogluconate 900 mg/m2/day will be given on d1-5 and d15-19. 28 days per cycle.

Sodium stibogluconate

Hui Zeng, MD

Huien Zhan, MD

Min Lu, PHD

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.

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.

Sodium Stibogluconate in the MDS/AML With One of the 65 Defined p53 Mutations

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

Partial response (PR) + complete response (CR) rate

Adverse events (AEs) will be reported and graded

Ruijin Hospital

First Affiliated Hospital of Jinan University

Director of Hematology Department of the First Affiliated Hospital of Jinan University

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Recurrence

Neoplasm Metastasis

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endometrial Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Uterine Neoplasms

Uterine Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

patients of recurrent and metastatic ovarian cancer and endometrial cancer associated with P53 mutation

Arsenic trioxide for injection, 0.16 mg/kg (maximum single dose is 10 mg), daily IV drip, d1 to d14, once every 28 days, for six cycles of treatment or until one of the following events occurs: Initiation of new anti-tumor therapy, disease progression, withdrawal of Informed consent form (ICF) and/or death.

Arsenic trioxide for injection

Tianjiao Lyu, PhD

Yahui Jiang, PhD

Weiwei Feng, PhD

This study is a Single-center, open, single-arm and non-randomized clinical trial in China. The aim of this study is to evaluate the efficacy, safety, and tolerability of Arsenic trioxide for injection in patients with recurrent and metastatic ovarian cancer and endometrial cancer with P53 mutation A group of 20 women with histologically confirmed ovarian cancer and endometrial cancer who had previously received at least one line of standard system therapy and had relapsed or metastasized had a P53 mutation.

The subjects of this study are histologically confirmed ovarian cancer and endometrial cancer patients with P53 mutation who had relapsed or metastasized after at least one line of standard system therapy. 20 subjects will be enrolled in this study.

Main objectives of the study are Independent imaging and tumor markers assess ORR (objective response rate) in patients with recurrent and metastatic ovarian cancer and endometrial cancer with P53 mutation treated with Arsenic trioxide for injection, based on RECIST v1.1 （Response evaluation criteria in solid tumors） Secondary objectives including DCR (Disease control rate), CBR (Clinical benefit rate), PFS (Progression free survival), OS (Overall survival), DoR (Duration of response), safety and tolerability of Arsenic trioxide for injection, based on NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events), evaluated by researchers and life quality.

The study will be conducted in the department of obstetrics and gynecology in Shanghai Jiaotong University School of Medicine affiliated Ruijin Hospital.

Research intervention: injection Arsenic trioxide, 0.16mg/kg (maximum single dose is 10 mg), daily IV drip, d1 to d14, once every 28 days, for six cycles of treatment or until one of the following events occurs: Initiation of new anti-tumor therapy, disease progression, withdrawal of Informed consent form (ICF) and/or death.

The duration of this study will be 2.5 years; the admission period will be 1.5 years and the follow-up period will be 1 year.

The P53 mutation plays an important role in the development of ovarian cancer and endometrial cancer, which has been found to occur in more than 95% of high grade serous ovarian cancers, 25% of the endometrial cancer, with serous endometrial cancer having a P53 mutation rate of 88%.

In Acute promyelocytic leukemia treatment, a combination of retinoic acid (ATRA) and Arsenic trioxide (ATO) has an extremely high cure rate, with an overall five-year survival rate of 88% , the therapeutic effect of ATO on some hematologic malignancies has been widely recognized. What's more, it is also found that arsenic has potential therapeutic effects on a variety of solid tumors, including Esophageal, liver and lymphoma.

Preciously research modified H1299 cells with structural mutant P53 (p53-R175H) and treated them with doxcycline to knock down p53-R175H. The system was able to determine whether the observed antitumor effects were dependent on the structural mutant p53. In the transplanted tumor model of this cell line in mice, ATO significantly inhibited the tumor growth rate. In mice fed with doxcycline, cancer cells expressed almost no P53-R175H, and the ATO had limited inhibitory effect on the transplanted tumor model. These results suggest that ATO inhibits tumor cell proliferation mainly by targeting structural mutant p53.

Researchers tested the antineoplastic effects of ATO on various solid tumor PDX models on a small scale. the results showed than the antineoplastic effect of ATO on the PDX (Patient-Derived tumor Xenograft) model was observed in several solid tumor models with structural mutant P53, including liver, Lung, and Pancreatic Cancer. This suggests that the antineoplastic effects of ATO are not limited to the types of cancer. Its anti-tumor effect is only related to the structural mutant p53 in cancer cells.

Previous studies have shown that Arsenic trioxide can bind to the structural mutant P53 and partially restore its function, so the goal of this study is to observe the efficacy, safety, and tolerability of Arsenic trioxide for injection in patients with recurrent and metastatic ovarian cancer and endometrial cancer combined with P53 mutation.

Histologically confirmed ovarian cancer and endometrial cancer patients with P53 mutation who had relapsed or metastasized after at least one line of standard system therapy. 20 subjects will be enrolled in this study.

Female patients woth ovarian cancer or endometrial cancer.

Arsenic Trioxide in Recurrent and Metastatic Ovarian Cancer and Endometrial Cancer With P53 Mutation

A Clinical Trial to Evaluate the Efficacy, Safety, and Tolerability of Arsenic Trioxide for Injection in Patients With Recurrent and Metastatic Ovarian Cancer and Endometrial Cancer With P53 Mutation

The retraction degree of the lesion which was detected in the beginning of the study (measured by CT, MRI or ultrasound).

the level of CA125 (carbohydrate antigen 125), HE4 (human epididymis protein 4) or other abnormal tumor markers in serum.

Nervous System Diseases

Glioblastoma

Glioma

Brain Neoplasms

Neoplastic Cells, Circulating

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Neuroepithelioma

Glioblastomas, the most frequent malignant brain tumor in adults, are widespread in the brain, despite their discrete appearance on computed tomography (CT) or magnetic resonance imaging (MRI). While this tumor tends to spread widely in the brain, unlike other tumors of the body, it rarely metastasizes, or spreads, to other organs. Approximately 10 percent of patients with glioblastoma develop metastatic disease after radiation or brain surgery. In the absence of radiation or brain surgery, few patients have developed disease spread outside the brain.

During surgery to remove tumors of other organs of the body, such as the lung, prostate, kidney, or ovary, cells from these tumors are routinely found in the bloodstream. These cells are believed to be the reason for the spread of these tumors. In the case of malignant brain tumors, this process of glioma (tumor) cells shedding into circulation has not yet been investigated.

This study will determine whether glioma cells can be detected in the bloodstream of patients undergoing surgery. If glioma cells are absent, it may mean they are unable to penetrate the blood-brain barrier. If they are present, they presumably can penetrate into blood vessels but they may be recognized and eliminated by the immune system, or they may escape detection yet not be able to take hold in the new microenvironment. The results of the study will add to the knowledge of the biology of these highly malignant tumors.

Study participants will be admitted to the hospital for 8 to 10 days. They will undergo a complete physical and neurological exam and blood and urine tests. An electrocardiogram will be performed, and x-rays may be taken. On the morning of surgery, the patient will receive sedation intravenously. A tiny plastic tube called a catheter will be introduced into a vein in the groin through needles. The catheter will be passed through to the jugular bulb, right above the jugular vein, on the same side as the tumor. The patient will then be taken to the operating room for surgery. During surgery, not more than one quarter of a unit of blood will be removed through the catheter. The catheter will be removed before the patient enters the intensive care unit. Another MRI will be taken after surgery.

The study will enroll participants for 2 years. Patients will be followed at 3 months and 6 months after the surgery to make sure the postoperative period is uneventful.

Glioblastomas are the most frequent malignant brain tumor in adults and are widespread in the brain despite their discrete appearance on CT or MRI. While locally aggressive, metastasis of glioblastoma to extracranial organs is considered rare. Approximately 10% of patients with glioblastoma develop metastatic disease after radiation or craniotomy. Few patients have developed extracranial metastatic disease in the absence of surgical resection or radiation. Unlike tumors of other organs such as lung, colon and prostate, the presence of glioma cells in the circulation of patients undergoing surgical resection has not been established. If found absent, glioma cells may be unable to intravasate through the blood brain barrier. If present, these tumor cells presumably can intravasate but may be recognized and eliminated by an immunological process, or they may escape detection yet not be able to take hold in the new microenvironment. The information provided will add to the knowledge of the biology of these highly malignant tumors.

Detecting Malignant Brain Tumor Cells in the Bloodstream During Surgery to Remove the Tumor

Detection of Glioblastoma or Anaplastic Astrocytoma Cells in the Circulation During Surgical Resection

National Institute of Neurological Disorders and Stroke (NINDS)

Nutritional and Metabolic Diseases

Diseases and Abnormalities at or Before Birth

Mitochondrial Diseases

Li-Fraumeni Syndrome

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

DNA Repair-Deficiency Disorders

Metabolic Diseases

60 non-carrier LFS family members or normal

20 non-carrier mitochondrial disorder family members or normal controls

30 normal controls for MR spectroscopy study

Paul M Hwang, M.D.

This study will examine metabolic and biological factors in people with Li-Fraumeni syndrome, a rare hereditary disorder that greatly increases a person's susceptibility to cancer. Patients have a mutation in the p53 tumor suppressor gene, which normally helps control cell growth. This gene may control metabolism as well as cancer susceptibility, and the study findings may help improve our understanding of not only cancer but also other conditions, such as cardiovascular function.

Healthy normal volunteers and patients with the Li-Fraumeni syndrome and their family members may be eligible for this study. Candidates must be at least 18 years of age, in overall good health and cancer-free within 1 year of entering the study. Participants undergo the following procedures:

* Blood tests for routine lab values and for research purposes.
* ECG and echocardiogram (heart ultrasound) to evaluate heart structure and function.
* Resting and exercise metabolic stress testing: The subject first relaxes in a chair wearing the facemask and then exercises on a stationary bicycle or treadmill while wearing the mask. This test uses the facemask to measure oxygen usage by the body to determine metabolic fitness. Electrodes are placed on the body to monitor the heart in an identical manner to a standard exercise stress test.
* Magnetic resonance imaging of metabolism: The subject lies on a bed that slides into a large magnet (the MRI scanner) for up to 60 minutes. During scanning, the arm or leg muscles are stressed by inflating a blood pressure cuff and by exercising the limb for several minutes. Subjects may be asked to squeeze a rubber ball or exercise with a foot pedal. Immediately afterwards, the pressure in the cuff is released and remains deflated for 10 to 15 minutes. No more than three 5-minute episodes of blood flow stoppage are performed.
* Standard MRI scan of exercised limb to determine muscle volume.
* Brachial artery reactivity test to measure blood vessel function: Before the exercise stress testing, subjects lie on a stretcher while the brachial artery (artery in the forearm) is imaged using a noninvasive ultrasound method. Artery size and blood flow velocity are measured before and after inflating a blood pressure cuff on the forearm. Vessel size and flow velocity measurements are repeated after 15 minutes and again after administration of nitroglycerin under the tongue.
* Oral glucose tolerance testing to test for diabetes: To assess sugar metabolism, subjects drink a sugar solution. Blood samples are collected before drinking the solution and 1 and 2 hours after drinking the solution.
* Muscle biopsy (optional according to subject preference): Subjects may be given small amounts of sedation for the procedure. A small area of skin over a leg muscle is numbed and a small amount of muscle tissue is surgically removed.

We have previously reported that TP53 (encoding p53 protein), one of the most frequently mutated genes in human cancers, dose dependently modulates the balance between the utilization of oxidative and glycolytic pathways for energy generation in human colon cancer cells and mouse liver mitochondria. Though morphologically similar to their wild-type littermates, mice deficient in p53 display a gene dose-dependent decrease in aerobic exercise capacity, implying that p53 has functions beyond its well characterized cell cycle activities. These current findings have broad implications in fields ranging from cancer and aging research to cardiovascular physiology.

In the Li-Fraumeni familial cancer syndrome (LFS), affected individuals harbor a germline mutation in TP53, hence they are heterozygous with reduced wild-type p53 activity. We hypothesize that the heterozygous individuals will display alterations in aerobic capacity and metabolism that previously has been unappreciated. This IRB proposal translates our experimental observation to human subjects in collaboration with extramural groups studying this rare familial syndrome. The results may not only help clarify why mutations of p53 gene are so common in cancers by potentially conferring metabolic advantages in tumorigenesis, but they may also give us an opportunity to understand a fundamental regulatory mechanism in cellular energy generation relevant to other processes.

Role of p53 Gene in Metabolism Regulation in Patients With Li-Fraumeni Syndrome

Metabolic Regulation by Tumor Suppressor p53 in Li-Fraumeni Syndrome

Because an interim analysis has confirmed our hypothesis, the aim of the primary endpoint has been achieved.

This will serve to facilitate bench-to-bedside studies to investigate metabolic and other associated changes in LFS with the goal of deriving mechanistic insights that may lead to new strategies forcancer prevention.

National Heart, Lung, and Blood Institute (NHLBI)

decitabine: 20mg/m2/d, intravenously, d1-d5, q4w arsenic trioxide: 0.16mg/kg/d, intravenously, d1-d5, q4w(maximum dose: 10mg/d)

0.16mg/kg/d, intravenously, d1-d5, q4w(maximum dose: 10mg/d)

Min Lu, PhD

Sujiang Zhang, MD, PhD

Sujiang Zhang, PhD

TP53 mutation is commonly associated with poor cancer patient prognosis yet no mutant p53 (mp53)-targeting regimen was clinically established. Here the investigators try to evaluate the side effect and treatment potential of DAC+ATO in p53 mutated high-risk AML/MDS patients.

About 200 AML/MDS patients will be sequenced for TP53 sequence before recruitment. The investigators estimated about 5 patients, based on the reported p53 mutation frequency in AML/MDS, will be p53-mutated. In the trial, the investigators will selectively recruit the mp53 AML/MDS patients that are predicted to respond to DAC+ATO regimen with highest chance (based on the relevant basic studies).

The investigators designate mutant p53-based clinical trials as 'PANDA (P53 AND Arsenic)-Trials'.

TP53 mutation is commonly associated with poor cancer patient prognosis yet no mutant p53 (mp53)-targeting regimen was clinically established. In two independent clinical trials reported recently, DNA demethylating drug Decitabine (DAC) treatment yielded a surprisingly high rate of complete remission (CR) in mp53-expressing myelodysplastic syndromes (MDS) patients and acute myeloid leukemia (AML) patients. Notably, all of the mp53-expressing patients in the two clinical studies, despite of CR, relapsed quickly. This was attributed to a failure in thoroughly clearing all leukemia-specific mutations and the preexisting mp53 subclone outgrew in all of the relapse patients. Indeed, The investigators also found p53 dysfunctional cells quickly develop a DAC resistance mechanism in cultured tissue (unpublished data). Meanwhile, the investigators found arsenic trioxide (ATO) selectively inhibit p53-mutated cells involving mutant p53 reactivation and mutant p53 degradation (presumably mediated by upregulated mdm2 and RCHY1/Pirh2 through reactivated mutant p53). In addition, DAC and ATO show synergy in inhibiting p53-mutated cells.

In current phase I trial, the investigators try to evaluate the side effect and treatment potential of DAC+ATO in p53 mutated high-risk MDS patients. About 200 AML/MDS patients will be recruited for TP53 sequencing before being trialed. The investigators estimated about 50 patients, based on p53 mutation frequency in AML/MDS, will be sequenced to be mp53-positive. The mp53-positive AML/MDS patients are known to have an extremely poor prognosis. The investigators will select high-risk mp53 MDS patients that are predicted to respond to DAC+ATO with highest chance based on our relevant basic studies.

The other participants (free of p53 mutation) will be excluded from the trial.

Mutant p53-based Personalized Trial Using Decitabine and Arsenic Trioxide on AML/MDS

Combination of Decitabine and ATO to Treat AML/MDS Expressing a Classified Type of Mutant p53

evaluate the side effects of current regimen

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Decitabine,Cytarabine and Arsenic Trioxide for Acute Myeloid Leukemia With p53 Mutations	NCT03381781	Acute Myeloid L... P53 Mutation	Decitabine Arsenic Trioxid... Cytarabine	18 Years - 75 Years	Ruijin Hospital
Decitabine and Arsenic Trioxide for Myelodysplastic Syndrome(MDS)	NCT03377725	Myelodysplastic... P53 Mutation	Decitabine Arsenic Trioxid...	18 Years - 75 Years	Ruijin Hospital
Sodium Stibogluconate in the MDS/AML With One of the 65 Defined p53 Mutations	NCT04906031	Myelodysplastic... Acute Myeloid L... Myeloid Maligna... Temperature-Sen... Sodium Stiboglu... P53 Mutation	Sodium stiboglu...	18 Years - 75 Years	First Affiliated Hospital of Jinan University
Decitabine and Arsenic Trioxide for Myelodysplastic Syndrome(MDS)	NCT03377725	Myelodysplastic... P53 Mutation	Decitabine Arsenic Trioxid...	18 Years - 75 Years	Ruijin Hospital
Arsenic Trioxide in Recurrent and Metastatic Ovarian Cancer and Endometrial Cancer With P53 Mutation	NCT04489706	Ovarian Cancer Endometrial Can...	Arsenic trioxid...	18 Years -	Ruijin Hospital
Detecting Malignant Brain Tumor Cells in the Bloodstream During Surgery to Remove the Tumor	NCT00001148	Astrocytoma Glioblastoma Glioma		-	National Institutes of Health Clinical Center (CC)
Arsenic Trioxide in Recurrent and Metastatic Ovarian Cancer and Endometrial Cancer With P53 Mutation	NCT04489706	Ovarian Cancer Endometrial Can...	Arsenic trioxid...	18 Years -	Ruijin Hospital
Role of p53 Gene in Metabolism Regulation in Patients With Li-Fraumeni Syndrome	NCT00406445	Mitochondrial D... Li-Fraumeni Syn... Carriers of p53...		18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Mutant p53-based Personalized Trial Using Decitabine and Arsenic Trioxide on AML/MDS	NCT03855371	P53 Mutation Myeloid Maligna... MDS Aml	Decitabine Arsenic Trioxid...	18 Years - 75 Years	Ruijin Hospital
Decitabine,Cytarabine and Arsenic Trioxide for Acute Myeloid Leukemia With p53 Mutations	NCT03381781	Acute Myeloid L... P53 Mutation	Decitabine Arsenic Trioxid... Cytarabine	18 Years - 75 Years	Ruijin Hospital
Decitabine and Arsenic Trioxide for Myelodysplastic Syndrome(MDS)	NCT03377725	Myelodysplastic... P53 Mutation	Decitabine Arsenic Trioxid...	18 Years - 75 Years	Ruijin Hospital

Spots Global Cancer Trial Database for p53 mutation

Every month we try and update this database with for p53 mutation cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.