A Trial to Investigate Whether Oral Arsenic Trioxide Is Similar to Intravenous Arsenic Trioxide in Pharmacokinetics, Safety, and Efficacy (LATITUDE/SDKARS-301) (LATITUDE)

LATITUDE - A Phase 3, Randomized, Open-Label, 3-Cohort, 2-Period, 2-Sequence, Crossover Trial to Evaluate the Pharmacokinetics, Safety, and Efficacy of Oral Arsenic Trioxide Versus Intravenous Arsenic Trioxide for Consolidation Therapy in Participants With Newly Diagnosed, Non-High-Risk, Acute Promyelocytic Leukemia

LATITUDE: A Phase 3, Randomized, Open-Label, 3-Cohort, 2-Period, 2- Sequence, Crossover Trial to Evaluate the Pharmacokinetics, Safety, and Efficacy of Oral Arsenic Trioxide Versus Intravenous Arsenic Trioxide for Consolidation Therapy in Participants With Newly Diagnosed, Non-High Risk, Acute Promyelocytic Leukemia

Rationale:

SDK Therapeutics is developing an oral formulation of arsenic trioxide (ATO) for the treatment of acute promyelocytic leukemia (APL). Patients with APL are usually treated with arsenic trioxide (ATO) through an IV along with all-trans retinoic acid (ATRA) taken by mouth. Receiving ATO through an IV requires patients with APL to go to the hospital a lot and get long treatments (sometimes every day over a year of treatment). This can be hard and uncomfortable. If ATO can be taken by mouth, it would be much easier for patients and their families.

Objective:

The main objective is to show that the body absorbs the same amount of ATO whether it's taken by mouth or through an IV. Other objectives include checking if ATO taken by mouth works just as well, causes fewer heart problems, is safe, and improves quality of life compared with ATO given through an IV.

Main trial endpoints:

The main endpoint being measured is how much ATO is in the blood after 5 doses. Another important endpoint is how many patients have no signs of cancer in their blood after 3 rounds of treatment.

Secondary trial endpoints:

Other things being measured include: whether patients stay cancer-free over 2 years; changes in heart rhythm; side effects and lab test results; how patients feel during treatment; how much of ATO is in the blood; and how often patients feel bothered by side effects.

Trial design:

This is an open-label study, meaning everyone knows which treatment they are getting. Patients will get 4 rounds of treatment, each lasting 8 weeks. After that, patients will have check-ups every 3 months to assess safety and disease status for a total of 2 years.

Trial population:

The study includes adults and teens (12 years and older) who have APL, are not high-risk, and have already finished the first part of their treatment (induction) with IV ATO and ATRA.

Interventions:

There are 3 groups in the study:

Cohort A: Takes 0.15 mg/kg Oral ATO for 3 rounds, then switches to 0.15 mg/kg IV ATO for part of the 4th round.

Cohort B: Takes 0.15 mg/kg IV ATO for 3 rounds, then switches to 0.15 mg/kg Oral ATO for part of the 4th round.

Cohort C: Takes 0.15 mg/kg Oral ATO for all 4 rounds.

All cohorts also take 45 mg/m2/day ATRA during certain weeks of each round. Doctors will assess efficacy by checking bone marrow samples before and during treatment to see if the cancer is gone. Special lab tests will be used to look for cancer cells. Safety will be assessed by checking for side effects using blood tests, heart tests, physical exams, and other health checks. Quality of life will be assessed by the patients who will fill out surveys about how they feel during treatment and how much the side effects bother them. The study will also look at how often patients need to go to the doctor or hospital; how treatment affects daily life and work; and how satisfied patients are with their treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Promyelocytic Leukemia; Leukemia, Acute; Acute Promyelocytic Leukemia With PML-RARA; Leukaemia; Acute Promyelocytic Leukaemia; Acute Promyelocytic Leukemia (APL); APL; Leukemia Acute Promyelocytic Leukemia (APL); Acute Promyelocytic Leukemia With t(15;17)(q24.1;q21.2); PML-RARA
• Intervention / Treatment: Drug: Oral ATO; Drug: IV Arsenic Trioxide; Drug: all-trans retinoic acid (ATRA)

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Danelle James, MD; Phone Number: +16196063187; Email: Danelle.James@sdktx.net
• Study Contact Backup: Name: Stephane Berthier, PharmD; Phone Number: +18628126042; Email: stephane.berthier@sdktx.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Participants must have diagnosis of newly diagnosed non-high risk APL with a WBC count at diagnosis ≤ 10,000 cells/µL, completed induction with ATO/ATRA and achieved morphologic CR with hematologic recovery
• Eastern Cooperative Oncology Group performance status ≤2
• Adequate liver, kidney, and cardiac function
• Have a life expectancy of at least 9 months
• Negative serum pregnancy test

Key Exclusion Criteria:

• Diagnosis of relapsed or refractory APL.
• Fridericia's corrected QT interval (QTcF) >450 milliseconds (males) and >460 milliseconds (females)
• Any gastrointestinal (GI) issue likely to affect oral drug absorption/metabolism or inability to swallow oral medication
• Prior malignancy or currently receiving treatment for a non-APL malignancy, with the following exceptions: basal cell or squamous cell skin cancer treated with surgical resection, in situ cervical cancer, localized prostate cancer or breast cancer treated with hormone therapy or surgical resection, or other cancer from which the participant has been disease free for at least 2 years.
• Pregnant or nursing females or is of reproductive potential and unwilling to comply with contraceptive requirements.
• Participant has known active or chronic hepatitis B or active hepatitis C (HCV) infection or human immunodeficiency virus (HIV)-positive with detectable viral load.

Note: Additional inclusion/exclusion criteria may apply, per protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Cohort A; Participants will receive Oral ATO 0.15 mg/kg daily × 5 days a week from Weeks 1 to 4 in the first three 8-week cycles, IV ATO 0.15 mg/kg daily (2-hour infusion) × 5 days in Week 1 of Cycle 4, and oral ATO 0.15 mg/kg daily × 5 days a week from Weeks 2 to 4 of Cycle 4. All adult participants will receive ATRA 45 mg/m2/day in 2 divided doses as background treatment 7 days a week for 2 weeks on and 2 weeks off (Weeks 1, 2, 5 and 6 of each 8-week cycle) beginning in Cycle 1 and ending after Cycle 4 Week 2	Drug: Oral ATO; Oral Arsenic Trioxide; Drug: IV Arsenic Trioxide; Intravenous Arsenic Trioxide; Drug: all-trans retinoic acid (ATRA); all-trans retinoic acid (ATRA)
Active Comparator: Part 1: Cohort B; Participants will receive IV ATO 0.15 mg/kg daily (2-hour infusion) × 5 days a week from Weeks 1 to 4 in the first three 8-week cycles, oral ATO 0.15 mg/kg daily × 5 days in Week 1 of Cycle 4, and IV ATO 0.15 mg/kg daily (2-hour infusion) × 5 days a week from Weeks 2 to 4 of Cycle 4. All adult participants will receive ATRA 45 mg/m2/day in 2 divided doses as background treatment 7 days a week for 2 weeks on and 2 weeks off (Weeks 1, 2, 5 and 6 of each 8-week cycle) beginning in Cycle 1 and ending after Cycle 4 Week 2	Drug: Oral ATO; Oral Arsenic Trioxide; Drug: IV Arsenic Trioxide; Intravenous Arsenic Trioxide; Drug: all-trans retinoic acid (ATRA); all-trans retinoic acid (ATRA)
Experimental: Part 2: Cohort C; Participants will receive Oral ATO 0.15 mg/kg daily × 5 days a week from Weeks 1 to 4 of four 8-week cycles. All adult participants will receive ATRA 45 mg/m2/day in 2 divided doses as background treatment 7 days a week for 2 weeks on and 2 weeks off (Weeks 1, 2, 5 and 6 of each 8-week cycle) beginning in Cycle 1 and ending after Cycle 4 Week 2	Drug: Oral ATO; Oral Arsenic Trioxide; Drug: all-trans retinoic acid (ATRA); all-trans retinoic acid (ATRA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic exposure (amount of ATO in the blood)	Total 5-dose plasma AsIII AUC	At the end of Cycle 4, Week 1 (Each cycle is 8 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular Complete Response (molCR) rate	molCR rate, defined as negative/undetected for PML:RARα by RT-qPCR	At the end of 3 Cycles of treatment (each cycle is 8 weeks)
Relapse-Free Survival (RFS)	2-year Relapse Free Survival (RFS)	Assessed for up to 2 years after the first dose of treatment, or until disease progression/relapse or death, whichever occurs first.
Change in Fridericia-corrected QT interval (ΔQTcF interval)	Difference in QTcF between collected values	At the end of Cycles 3 and 4 (each cycle is 8 weeks)
Adverse events	Frequency, severity, and relatedness of adverse events.	Up to 9 months
Cardiac AEs related to elevated QTcF	Number of prolonged QTcF interval or other arrhythmias per CTCAE	Up to 9 months
Pharmacokinetic profile	Peak Plasma Concentration (Cmax)	At the end of Cycle 4, week 1 (Each cycle is 8 weeks)
Patient Reported Outcomes	Change from baseline as measured by the EORTC QLQ-C30	Up to 9 months
Patient Reported Outcomes	Proportion of time "bothered by side-effects" as measured by the FACT-GP5	Up to 9 months

Collaborators and Investigators

• Sponsor: SDK Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: December 18, 2025
• First Posted (Estimated): December 22, 2025

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 25, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Oral Arsenic Trioxide; Oral ATO
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Hemic and Lymphatic Diseases; Leukemia; Leukemia, Promyelocytic, Acute; Organic Chemicals; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors; Inorganic Chemicals; Diterpenes; Oxides; Oxygen Compounds; Vitamin A; Arsenicals; Arsenic Trioxide; Tretinoin
• Other Study ID Numbers: SDKARS-301; 2025-524329-41-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No