SX-682 + Decitabine for Myelodysplastic Syndrome

Recruiting at 6 trial locations

Overseen By Aaron D Schuler, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Syntrix Biosystems, Inc.

Must not be taking: Chemotherapy, Erythroid stimulants

Disqualifiers: Cardiac abnormalities, Prior malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

151 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and recommended Phase 2 dose (RP2D) of SX-682 in the treatment of patients with Myelodysplastic Syndromes (MDS).

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, such as chemotherapeutic agents, experimental agents for MDS, erythroid stimulating agents, and some heart medications, at least 14 days before starting the study drug. If you are on medications that prolong the QT interval, you may need to stop them unless they are absolutely essential for your care.

What data supports the effectiveness of the drug SX-682 + Decitabine for Myelodysplastic Syndrome?

Decitabine, a component of the treatment, has shown effectiveness in treating myelodysplastic syndromes (MDS), with complete remission rates ranging from 9% to 34% and overall improvement rates from 30% to 73% in various studies. ^{1 2 3 4 5}

Is SX-682 + Decitabine safe for humans?

There is no specific safety data available for SX-682 combined with Decitabine, but Decitabine alone has been studied and found to be generally safe in patients with myelodysplastic syndrome (MDS). Common side effects include low blood cell counts and infections, but these are considered manageable. ^{6 7 8 9 10}

What makes the drug SX-682 + Decitabine unique for treating myelodysplastic syndrome?

The combination of SX-682 with Decitabine is unique because SX-682 is a novel drug that may work differently from existing treatments by targeting specific pathways involved in myelodysplastic syndrome, potentially offering a new approach to treatment when combined with Decitabine, which is already used to treat this condition. ^{3 7 11 12 13}

Research Team

David Sallman, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for adults with Myelodysplastic Syndromes (MDS) who have not responded to previous treatments. Participants must have an acceptable level of kidney function, be in a relatively stable condition (ECOG ≤ 2), and not be pregnant or breastfeeding. They should also use contraception if applicable and cannot join if they've had certain heart issues, other cancers within the last 3 years, HIV, Hepatitis B/C, or are on specific medications.

Inclusion Criteria

Not breastfeeding

WOCBP demonstrate negative pregnancy test

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I am allergic to one of the components in the study drug.

I have heart issues like abnormal ECG, recent heart attack, or use heart-related medications.

I haven't had any cancer except for local ones cured in the last 3 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of SX-682 to determine the maximum tolerated dose

Up to 28 days

Multiple visits for dose escalation and monitoring

Treatment

Participants receive SX-682 alone or in combination with decitabine for six 28-day cycles

24 weeks

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue SX-682 treatment if responding well until disease progression or adverse events

Indefinite

Treatment Details

Interventions

• SX-682

Trial Overview The study is testing SX-682 alone and combined with Decitabine taken orally or intravenously to find the safest dose that can be tolerated without severe side effects. It aims to establish what's called the maximum tolerated dose (MTD) and recommend a Phase 2 dose for further studies.

Participant Groups

Group I: Expansion of SX-682 with decitabine (lower risk patients, naive to hypomethylating agents) Experimental Treatment 2 Interventions

Expansion of oral doses of SX-682 (study drug) at 100 mg twice daily with decitabine in lower risk patients who have never received hypomethylating agents.

Group II: Expansion of SX-682 with decitabine (lower risk patients, failed on hypomethylating agents) Experimental Treatment 2 Interventions

Expansion of oral doses of SX-682 (study drug) at 100 mg twice daily with decitabine in lower risk patients who failed on hypomethylating agents.

Group III: Expansion of SX-682 with decitabine (higher risk patients, naive to hypomethylating agents) Experimental Treatment 2 Interventions

Expansion of oral doses of SX-682 (study drug) at 100 mg twice daily with decitabine in higher risk patients who have never received hypomethylating agents.

Group IV: Expansion of SX-682 with decitabine (higher risk patients, failed on hypomethylating agents) Experimental Treatment 2 Interventions

Expansion of oral doses of SX-682 (study drug) at 100 mg twice daily with decitabine in higher risk patients who failed on hypomethylating agents.

Group V: Expansion of SX-682 alone (lower risk patients, naive to hypomethylating agents) Experimental Treatment 1 Intervention

Expansion of oral doses of SX-682 (study drug) at 200 mg twice daily (recommended phase 2 dose) in lower risk patients who have never received hypomethylating agents.

Group VI: Expansion of SX-682 alone (lower risk patients, failed on hypomethylating agents) Experimental Treatment 1 Intervention

Expansion of oral doses of SX-682 (study drug) at 200 mg twice daily (recommended phase 2 dose) in lower risk patients who failed on hypomethylating agents.

Group VII: Expansion of SX-682 alone (higher risk patients, failed on hypomethylating agents) Experimental Treatment 1 Intervention

Expansion of oral doses of SX-682 (study drug) at 200 mg twice daily (recommended phase 2 dose) in higher risk patients who failed on hypomethylating agents.

Group VIII: Dose Escalation of SX-682 Experimental Treatment 1 Intervention

Escalating oral doses of SX-682 (study drug) of 25, 50, 100, 200 and 400 mg twice-daily (i.e., 50, 100, 200, 400 and 800 mg total each day.

Who Is Running the Clinical Trial?

Syntrix Biosystems, Inc.

Lead Sponsor

Trials

14

Recruited

810+

Montefiore Medical Center

Collaborator

Trials

468

Recruited

599,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborator

Trials

578

Recruited

33,600+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

University of Miami

Collaborator

Trials

976

Recruited

423,000+

H. Lee Moffitt Cancer Center and Research Institute

Collaborator

Trials

576

Recruited

145,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

AdventHealth

Collaborator

Trials

118

Recruited

31,800+

Findings from Research

In a study of 87 patients with myelodysplastic syndrome (MDS) treated with decitabine, 58.6% showed therapeutic responses, indicating that decitabine is an effective treatment option for MDS.

Factors such as high hENT1 mRNA expression and TP53 gene mutations were identified as independent prognostic indicators for better treatment outcomes, suggesting that these molecular markers can help predict which patients are more likely to respond to decitabine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Efficacy and Prognostic Factors of Decitabine for Treatment of Myelodysplastic Syndrome]. Bao, ZH., Zhao, HG., Yu, HE.[2019]

Decitabine, approved in the US since 2006 for myelodysplastic syndromes, shows variable complete remission rates, ranging from 9% in the initial trial to 34% in studies with new treatment schedules.

Overall improvement rates for decitabine treatment vary widely from 30% to 73%, indicating its potential effectiveness, but further research is needed to optimize its use compared to other treatments like azacitidine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine treatment of patients with higher-risk myelodysplastic syndromes. Steensma, DP.[2018]

Low-dose decitabine effectively reduces levels of soluble CD44 and GDF11 while improving hematopoietic function in elderly patients with myelodysplastic syndrome (MDS), showing a total effective rate of 82.3%.

This treatment also results in significantly fewer adverse reactions compared to standard and combination therapies, making low-dose decitabine a safer option for managing MDS in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of Low-Dose Decitabine on Soluble CD44, GDF11 Levels and Hematopoietic Function in Elderly Patients with MDS]. Guo, SQ., Shi, R., Chen, YY., et al.[2019]

In a study of 13 high-risk myelodysplastic syndromes (MDS) patients, decitabine treatment significantly reduced dysplastic changes in hematopoietic cells, indicating improved effectiveness of hematopoiesis.

The treatment with decitabine led to a restoration of cell differentiation and a decrease in myelodysplastic features across all cell lines, suggesting a positive response to therapy, while patients resistant to treatment showed no change in dysplastic cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Morphological evaluation of dysmyelopoiesis in decitabine-treated patients with myelodysplastic syndromes]. Dvirnyk, VN., Kokhno, AV., Glasko, EN., et al.[2018]

In a study of 107 elderly patients with myelodysplastic syndromes (MDS), the combination of decitabine (DAC) and thalidomide improved overall survival (OS) for high-risk patients compared to DAC alone, with a significant difference of 50.6% versus 40.2%.

While DAC plus thalidomide did not show a significant improvement in progression-free survival (PFS) or acute myeloid leukemia-free survival (AML-FS) compared to DAC monotherapy, thalidomide was well tolerated with no severe non-hematological toxicity, making it a safe alternative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine plus thalidomide yields more sustained survival rates than decitabine monotherapy for risk-tailored elderly patients with myelodysplastic syndrome. Zhao, WH., Zeng, QC., Huang, BT., et al.[2018]

In a study of 62 newly diagnosed lower-risk MDS patients, low-dose decitabine (12 mg·m(-2)·d(-1) for 5 days) resulted in a significantly higher overall response rate (66.7%) compared to best supportive care (29.6%), indicating its efficacy in treating this condition.

The treatment with decitabine also led to a statistically significant prolongation of progression-free survival compared to best supportive care (not reached vs 13.7 months), although it was associated with notable adverse effects, including high rates of neutropenia (45.8%) and infections (33.3%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A preliminary study on the outcome of lower-risk myelodysplastic syndrome by low-dose decitabine]. Ye, L., Ren, YL., Xie, LL., et al.[2020]

In a study of 11 patients with intermediate or high-risk myelodysplastic syndrome (MDS), the combination of low dose subcutaneous decitabine and arsenic trioxide resulted in 3 patients achieving complete remission and 6 showing hematological improvement.

The treatment appears to be a promising alternative regimen for MDS, with a median follow-up of 413 days and 9 out of 11 patients still alive at the end of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The safety and efficacy of low dose subcutaneous decitabine combined with arsenic trioxide in patients with inermediate or higer-risk myelodysplastic syndrome]. Ai, H., Wei, XD., Yin, QS., et al.[2020]

A 68-year-old woman with high-risk myelodysplastic syndromes (MDS) achieved complete remission after just one cycle of a combination therapy that included decitabine, cytarabine, and aclarubicin, along with haploidentical lymphocyte infusion.

The patient remained free of MDS relapse for 4 years post-treatment, indicating that this decitabine-based regimen may be a safe and effective option for elderly patients with high-risk MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of high-risk myelodysplastic syndrome with decitabine-based chemotherapy followed by haploidentical lymphocyte infusion: A case report and literature review. Ma, Y., Shen, J., Wang, LX.[2022]

In a study of 79 patients with acute myeloid leukemia and myelodysplastic syndromes, decitabine alone or in combination with CAG chemotherapy showed high overall response rates (ORR) of 53.3% to 69.2%, indicating its efficacy in treating these conditions.

All treatment groups tolerated decitabine well, with no treatment-related deaths reported, although there were significant adverse events such as infections and hematological toxicities, which were managed with supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The clinical efficacy of the patients of acute myeloid leukemia and myelodysplastic syndromes treated with decitabine alone, combined with half or one couse of CAG regimen]. Gao, S., Qiu, H., Jin, Z., et al.[2018]

In a phase I/II study involving 37 patients with myelodysplastic syndrome (MDS), decitabine was found to be safe, with manageable side effects, and showed efficacy with a complete response rate of 20.6% at a dosage of 20 mg/m².

The treatment led to significant hypomethylation in myeloid cells, which may contribute to its therapeutic effects, and resulted in a median duration of remission of over 474 days, with a 2-year acute myeloid leukemia-free survival rate of 52%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of decitabine in patients with myelodysplastic syndrome: a multi-center study in Japan. Oki, Y., Kondo, Y., Yamamoto, K., et al.[2021]

This case study reports the successful use of decitabine and lenalidomide in treating a patient with myelodysplastic syndrome (MDS) characterized by a 5q deletion and elevated blast counts, leading to significant improvements in hemoglobin levels and cessation of transfusion dependency after just two cycles.

The treatment combination was well-tolerated with no notable side effects, suggesting it could be a promising option for MDS patients with similar profiles, although further validation in larger studies is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide Plus Decitabine Treatment in a Myelodysplastic Syndrome Patient With Deletion 5q and Excess Blasts. Serin, I., Eren, R., Dogu, MH.[2020]

In a phase III trial involving patients aged 60 and older with myelodysplastic syndromes (MDS), decitabine treatment resulted in a 15% complete or partial remission rate and significantly improved progression-free survival (PFS) and overall survival (OS) compared to best supportive care.

Specifically, patients with refractory anemia with excess blasts in transformation (RAEBt) treated with decitabine had a median PFS of 6.2 months versus 2.8 months in the supportive care group, indicating that decitabine is an effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG). Becker, H., Suciu, S., Rüter, BH., et al.[2018]

In mouse models of MDS and AML, acute loss of p53 decreased the sensitivity of cancer cells to decitabine, indicating that short-term inhibition of p53 can lead to resistance against this treatment.

However, long-term deficiency of p53 in AML cells increased their sensitivity to decitabine, suggesting that the role of p53 in response to treatment is complex and may vary depending on the duration of its loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opposing effects of acute versus chronic inhibition of p53 on decitabine's efficacy in myeloid neoplasms. Tamura, M., Yonezawa, T., Liu, X., et al.[2021]

References

1. China pubmed.ncbi.nlm.nih.gov

[Clinical Efficacy and Prognostic Factors of Decitabine for Treatment of Myelodysplastic Syndrome]. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Decitabine treatment of patients with higher-risk myelodysplastic syndromes. [2018]

3. China pubmed.ncbi.nlm.nih.gov

[Effects of Low-Dose Decitabine on Soluble CD44, GDF11 Levels and Hematopoietic Function in Elderly Patients with MDS]. [2019]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Morphological evaluation of dysmyelopoiesis in decitabine-treated patients with myelodysplastic syndromes]. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Decitabine plus thalidomide yields more sustained survival rates than decitabine monotherapy for risk-tailored elderly patients with myelodysplastic syndrome. [2018]

6. China pubmed.ncbi.nlm.nih.gov

[A preliminary study on the outcome of lower-risk myelodysplastic syndrome by low-dose decitabine]. [2020]

7. China pubmed.ncbi.nlm.nih.gov

[The safety and efficacy of low dose subcutaneous decitabine combined with arsenic trioxide in patients with inermediate or higer-risk myelodysplastic syndrome]. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Successful treatment of high-risk myelodysplastic syndrome with decitabine-based chemotherapy followed by haploidentical lymphocyte infusion: A case report and literature review. [2022]

9. China pubmed.ncbi.nlm.nih.gov

[The clinical efficacy of the patients of acute myeloid leukemia and myelodysplastic syndromes treated with decitabine alone, combined with half or one couse of CAG regimen]. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Phase I/II study of decitabine in patients with myelodysplastic syndrome: a multi-center study in Japan. [2021]

11. Canada pubmed.ncbi.nlm.nih.gov

Lenalidomide Plus Decitabine Treatment in a Myelodysplastic Syndrome Patient With Deletion 5q and Excess Blasts. [2020]

12. Germany pubmed.ncbi.nlm.nih.gov

Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG). [2018]

13. England pubmed.ncbi.nlm.nih.gov

Opposing effects of acute versus chronic inhibition of p53 on decitabine's efficacy in myeloid neoplasms. [2021]