A Study for Oral SY-2101 for Participants With Acute Promyelocytic Leukemia

Recruiting at 12 trial locations

Overseen By Medical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Syros Pharmaceuticals

Must be taking: ATO, ATRA

Disqualifiers: Non-APL cancer, HIV, Hepatitis, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

16 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing SY-2101, an oral form of a drug used to treat leukemia, in patients with acute promyelocytic leukemia (APL) who are in remission. The goal is to see if taking the drug by mouth is as effective as the current IV method in preventing the cancer from coming back. Bisantrene, a new drug, has shown effectiveness in treating leukemia with manageable side effects.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you will continue receiving treatment with ATO and ATRA as part of the study.

What safety data exists for arsenic trioxide in humans?

Arsenic trioxide has been used for treating certain types of leukemia and other cancers, but it can cause side effects like skin reactions, stomach upset, and liver issues. Serious heart problems, including arrhythmias (irregular heartbeats), can occur, especially in people with existing heart conditions or electrolyte imbalances. The oral form may have fewer heart-related side effects compared to the intravenous form. ^{1 2 3 4 5}

How is the drug arsenic trioxide unique in treating certain cancers?

Arsenic trioxide is unique because it can induce complete remission in over 80% of patients with relapsed acute promyelocytic leukemia (APL) and is effective in other leukemia types when combined with other drugs. It has a long history of medicinal use and is being explored for its potential in treating various cancers due to its ability to target cancer cells specifically. ^{6 7 8 9 10}

Research Team

Medical Director, MD

Principal Investigator

Syros Pharmaceuticals Inc.

Eligibility Criteria

Inclusion Criteria

Participants must have a serum or high-sensitivity urine pregnancy test (for females of childbearing potential) that is negative at the Screening Visit and immediately prior to initiation of study treatment (first dose of study drug).

Participants must have a diagnosis of APL characterized by the presence of the t(15;17) translocation or PML/RARA gene expression via reverse transcription polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), or cytogenetics. Participants with low-risk APL may be eligible for all parts of this study; participants with high-risk APL are only eligible for the single-dose modules if they have completed a treatment regimen that included ATO within 6 months prior to the Screening Visit.

Participants must have received ATO plus ATRA induction therapy and must have received or be eligible and planning to receive consolidation therapy with ATO plus ATRA in alignment with National Comprehensive Cancer Network (NCCN) guidelines for low-risk APL prior to their enrollment in the study; or participants must have completed a treatment regimen that included ATO within 6 months prior to the Screening Visit.

Exclusion Criteria

Participants who have a hypersensitivity to arsenic.

Participants who have demonstrated relapse and therefore are not eligible for further consolidation.

Participants currently receiving treatment for a non-APL malignancy (not including basal cell carcinoma, non-melanoma skin cancer, cervical carcinoma in situ, or localized prostate cancer treated with hormone therapy). Participants with history of other cancers should be free of disease for at least 2 years prior to the Screening Visit.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Single-Dose PK Module

Participants receive a single dose of IV ATO, followed by a single dose of SY-2101 in fed or fasted conditions, with blood draws and safety assessments after each dose.

3 weeks

3 visits (in-person)

Part 2: Multiple-Dose IV Module

Participants receive IV ATO according to the standard of care, with blood collection and safety assessments.

4 weeks

5 visits (in-person)

Part 3: Multiple-Dose Oral Module

Participants in molecular remission receive SY-2101 in place of IV ATO during the 4th cycle of consolidation, with blood collection and safety assessments.

4 weeks

5 visits (in-person)

Part 4: Single-Dose PK Comparability Module

Participants receive two single-dose treatments of SY-2101 approximately one week apart.

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Arsenic Trioxide
• SY-2101

Participant Groups

Group I: Single-Dose PK Module: Sequence 2 Experimental Treatment 2 Interventions

Participants will receive IV ATO in a fasted state on Day 1, SY-2101 in a fasted state on Day 8, and SY-2101 in a fed state on Day 15 during Weeks 6, 7, and 8 of any consolidation cycle being received as part of SOC treatment consolidation cycle.

Group II: Single-Dose PK Module: Sequence 1 Experimental Treatment 2 Interventions

Participants will receive IV ATO in a fasted state on Day 1, SY-2101 in a fed state on Day 8, and SY-210 in a fasted state on Day 15 during Weeks 6, 7, and 8 of any consolidation cycle being received as part of SOC treatment consolidation cycle.

Group III: Single-Dose PK Comparability Module Experimental Treatment 1 Intervention

Participants will receive two single-dose treatments of SY-2101, with separated from one another by approximately 1 week and separated from any preceding IV ATO dose by at least 72 hours.

Group IV: Multiple-Dose Oral Module Experimental Treatment 1 Intervention

Participants will receive SY-2101, QD, 5 days/week for 28 days as a part of one cycle (Cycle 4; Weeks 1 through 4) of SOC treatment consolidation.

Group V: Multiple-Dose IV Module Experimental Treatment 1 Intervention

Participants will receive IV ATO, once daily (QD), 5 days/week for 28 days as a part of at least one cycle (Weeks 1 through 4) of SOC treatment consolidation.

Arsenic Trioxide is already approved in United States, European Union for the following indications:

Approved in United States as Trisenox for:

• Acute promyelocytic leukemia (APL)

Approved in European Union as Trisenox for:

• Acute promyelocytic leukemia (APL)

Who Is Running the Clinical Trial?

Syros Pharmaceuticals

Lead Sponsor

Trials

6

Recruited

1,000+

Findings from Research

Arsenic trioxide is highly effective in treating acute promyelocytic leukemia (APL), achieving complete remissions in over 80% of relapsed patients and molecular remission in 90% of those who reach complete remission.

Clinical trials indicate that arsenic trioxide not only benefits relapsed APL patients but also shows promise in first-line treatment and consolidation therapy, improving event-free and overall survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New data with arsenic trioxide in leukemias and myelodysplastic syndromes. Sekeres, MA.[2019]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Biocompatible arsenic trioxide nanoparticles induce cell cycle arrest by p21(WAF1/CIP1) expression via epigenetic remodeling in LNCaP and PC3 cell lines. [2018]

2. Japan pubmed.ncbi.nlm.nih.gov

Arrhythmogenic effects of arsenic trioxide in patients with acute promyelocytic leukemia and an electrophysiological study in isolated guinea pig papillary muscles. [2019]

3. Italy pubmed.ncbi.nlm.nih.gov

Myocardial toxicity of acute promyelocytic leukaemia drug-arsenic trioxide. [2018]

4. China pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of intravenous arsenic trioxide in the treatment of acute promyelocytic leukemia. [2018]

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

Arsenic trioxide: safety issues and their management. [2018]

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

[Arsenic trioxide induced apoptosis and expression of p53 and bcl-2 genes in human small cell lung cancer cells]. [2018]

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

Anticancer activity of small-molecule and nanoparticulate arsenic(III) complexes. [2021]

8. China pubmed.ncbi.nlm.nih.gov

[Cytotoxic effects of arsenic trioxide in combination with chemotherapeutic drugs on acute non-promyelocytic leukemia cells]. [2021]

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

Effect of arsenic trioxide on rat hepatocellular carcinoma and its renal cytotoxity. [2019]

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

New data with arsenic trioxide in leukemias and myelodysplastic syndromes. [2019]