SY-2101 for Acute Promyelocytic Leukemia

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests SY-2101, an oral version of the drug arsenic trioxide (ATO), for treating acute promyelocytic leukemia (APL). The researchers aim to determine if oral ATO can be as effective as the traditional intravenous method in maintaining APL remission. Participants will alternate between receiving traditional IV ATO and the new oral SY-2101 during treatment cycles. The trial seeks individuals with APL in remission who are already receiving standard treatment with ATO and ATRA and have completed their initial treatment phase within the past 6 months. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new oral treatment.

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.

Is there any evidence suggesting that SY-2101 is likely to be safe for humans?

Research has shown that SY-2101, a pill form of arsenic trioxide (ATO), has been tested for safety in adults with acute promyelocytic leukemia (APL). In earlier studies, SY-2101 demonstrated safety results similar to the traditional intravenous (IV) form of ATO. Most participants tolerated the pill form well, experiencing only mild to moderate side effects.

The IV form of arsenic trioxide is already approved for treating APL, providing extensive knowledge about its safety. Common side effects of ATO include nausea and tiredness, but these are usually manageable.

Overall, early results suggest that the pill version, SY-2101, could serve as a convenient alternative to the IV form, with similar safety. However, as these are early studies, further research is underway to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SY-2101 for treating Acute Promyelocytic Leukemia (APL) because it offers a potentially more convenient alternative to the standard treatment, Arsenic Trioxide (ATO), which is typically administered intravenously (IV). Unlike the IV formulation, SY-2101 is an oral medication, making it easier for patients to take and potentially improving their quality of life. Additionally, this oral form could simplify the treatment process by reducing the need for frequent hospital visits. This new delivery method could make a significant difference for patients, offering them a less invasive way to receive their therapy.

What evidence suggests that SY-2101 could be an effective treatment for acute promyelocytic leukemia?

Research has shown that arsenic trioxide (ATO) effectively treats acute promyelocytic leukemia (APL), helping patients achieve remission, where cancer symptoms disappear. ATO is often combined with all-trans-retinoic acid (ATRA) for improved outcomes. In this trial, participants will receive either the oral version, SY-2101, or the intravenous (IV) form of ATO. A study comparing these forms suggested they work equally well. The oral form could make treatment more convenient without losing effectiveness. These findings support SY-2101 as a promising option for APL treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

Medical Director, MD

Principal Investigator

Syros Pharmaceuticals Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Arsenic Trioxide
• SY-2101

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4305381/

A Review of Arsenic Trioxide and Acute Promyelocytic Leukemia It has been demonstrated that this drug is effective against all stages of acute promyelocytic leukemia, including for remission induction of relapsed cases, or ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00517712

Single Agent Arsenic Trioxide in the Treatment of Newly ... Studies from our centre have shown remission rates of 70-75% in newly diagnosed patients with acute promyelocytic leukemia. There was no major ...

3. pnas.org pnas.org/doi/10.1073/pnas.0813280106

Long-term efficacy and safety of all-trans retinoic acid ... These results demonstrate the high efficacy and minimal toxicity of ATRA/ATO treatment for newly diagnosed APL in long-term follow-up.

4. ashpublications.org ashpublications.org/blood/article/94/6/2102/175717/Arsenic-Trioxide-Selectively-Induces-Acute

Arsenic Trioxide Selectively Induces Acute Promyelocytic ... Abstract. Low concentrations of As2O3 (≤1 μmol/L) induce long-lasting remission in patients with acute promyelocytic leukemia (APL) without significant mye.

5. mayoclinic.org mayoclinic.org/drugs-supplements/arsenic-trioxide-intravenous-route/description/drg-20062068

Arsenic trioxide (intravenous route) - Side effects & uses Arsenic trioxide injection is used together with another medicine (eg, tretinoin) to treat newly-diagnosed low-risk acute promyelocytic leukemia (APL).

6. fishersci.com fishersci.com/store/msds?partNumber=AC211040250&productDescription=ARSENIC+%28III%29+OXIDE%2C+P.A+25GR&vendorId=VN00032119&countryCode=US&language=en

SAFETY DATA SHEET N/A. Page 4. Arsenic(III) oxide. Revision Date 24-Dec-2021. Do not get in eyes, on skin, or on clothing. Do not ingest. If swallowed then seek ...

7. sigmaaldrich.com sigmaaldrich.com/sds/sigald/311383?srsltid=AfmBOoqbK7yt7_TExR5vb6xEIz0WDoE8aj1aD1PPrheyAu6yiihPro1S

SAFETY DATA SHEET Chronic aquatic toxicity. : Very toxic to aquatic life with long lasting effects. Persistence and degradability. Components: Arsenic trioxide:.

8. assets.thermofisher.com assets.thermofisher.com/DirectWebViewer/private/results.aspx?page=NewSearch&LANGUAGE=d__EN&SUBFORMAT=d__CGV4&SKU=ALFAA43488&PLANT=d__ALF

SAFETY DATA SHEET This product does not contain any known or suspected endocrine disruptors. SECTION 3. COMPOSITION/INFORMATION ON INGREDIENTS. Component. CAS No.

9. nj.gov nj.gov/health/eoh/rtkweb/documents/fs/0161.pdf

Arsenic Trioxide This Fact Sheet is a summary of available information regarding the health hazards that may result from exposure. Duration of exposure, concentration of the ...

10. sigmaaldrich.com sigmaaldrich.com/sds/sigald/a1010?srsltid=AfmBOorTbtcS_bYbhSwVH_aV55sSIFqgJf7LLW-L1C7euYrsN1bRTHun

SAFETY DATA SHEET Arsenic oxides. Not combustible. Ambient fire may liberate hazardous vapours. 5.3 Advice for firefighters. Stay in danger area only with self- ...