Clinical Research Directory

Early Use of Realgar-Indigo Naturalis Formula (RIF) Combined With All-trans Retinoic Acid (ATRA) for Treating Acute Promyelocytic Leukemia (APL).

Study Title: Multicenter, Randomized Controlled Clinical Study on Early Application of Realgar-Indigo Naturalis Formula (RIF) for Treatment of Acute Promyelocytic Leukemia (APL) Sponsor: Xi'an Jiaotong University First Affiliated Hospital Principal Investigator: Wang Huaiyu Study Description: This multicenter, randomized controlled trial evaluates whether early induction treatment with oral Realgar-Indigo Naturalis Formula (RIF) combined with all-trans retinoic acid (ATRA) reduces early death rates in patients with acute promyelocytic leukemia (APL). APL is a subtype of acute myeloid leukemia characterized by a high risk of early death, largely due to coagulopathy and bleeding events, especially in high-risk patients with elevated white blood cell counts. Traditional treatment with ATRA and arsenic trioxide (ATO) has improved outcomes but early mortality remains a major challenge. RIF, an oral arsenic compound Chinese patent medicine, has demonstrated efficacy comparable to ATO with advantages in safety and oral administration convenience. Previous smaller studies suggested RIF may accelerate recovery of coagulation parameters and reduce early death. Patients clinically suspected of APL will be randomized into two groups: Experimental group: oral ATRA + RIF before molecular diagnosis confirmation Control group: oral ATRA only before confirmation After molecular or genetic diagnosis confirmation: Experimental group receives 1 week of ATRA + RIF induction (days 0-7), then switches to 3 weeks ATRA + ATO (days 8-28) Control group receives 4 weeks ATRA + ATO (days 0-28) Both groups then receive identical consolidation therapy with ATRA + ATO for 6 cycles (2 weeks treatment + 2 weeks off per cycle) following molecular complete remission. Primary Objective: To evaluate whether early induction with ATRA + RIF reduces early death rate (within 30 days of diagnosis) in APL patients. Secondary Objectives: To explore if early ATRA + RIF (prior to molecular confirmation) is non-inferior to ATRA alone in reducing coagulopathy and early death in suspected APL patients. Secondary endpoints include 2-year event-free survival (EFS) and overall survival (OS). Study Design: Type: Multicenter, randomized, open-label controlled clinical trial Population: Adults aged 18-80 years with newly diagnosed acute myeloid leukemia highly suspected as APL Randomization: Central randomization assigns participants to experimental (ATRA + RIF) or control (ATRA only) groups Blinding: Open-label (no blinding) Inclusion Criteria: Age 18-80 Newly diagnosed AML with strong clinical suspicion of APL based on bone marrow morphology and immunophenotyping Exclusion Criteria: Negative for PML-RARα fusion by cytogenetics or RT-PCR Severe organ dysfunction not related to APL (renal, hepatic, cardiac) QTc \>480 ms before treatment Other malignancies Pregnant or breastfeeding women Treatment Regimen: Induction: Experimental group receives oral ATRA 25 mg/m²/day + RIF 60 mg/kg/day for 7 days, then ATRA + intravenous ATO 0.15 mg/kg/day for 3 weeks; Control group receives ATRA + ATO for 4 weeks. Consolidation:During the consolidation phase, intermediate- and low-risk patients receive either intravenous ATO or oral RIF, while high-risk patients receive intravenous ATO together with intravenous mannitol infusion. Routine lumbar puncture and intrathecal chemotherapy are not performed. Supportive care includes hydroxyurea and venetoclax for elevated WBC, transfusions for coagulopathy, and dexamethasone for differentiation syndrome. Endpoints: Primary endpoint: Early death rate (death within 30 days of diagnosis) Secondary endpoints: 2-year event-free survival (EFS), 2-year overall survival (OS) Sample Size: Approximately 224 patients (112 per group), calculated to detect a reduction in early death rate from 12% (historical) to 3% (experimental), with 80% power and 5% significance level. Statistical Analysis: Descriptive statistics for baseline characteristics and adverse events Kaplan-Meier survival analysis for EFS and OS Significance threshold p \< 0.05 Safety Monitoring: Daily blood count and coagulation tests during induction Monitoring and management of adverse events including severe coagulation disorders, differentiation syndrome, arsenic toxicity, infection, and bone marrow suppression Adverse events graded with CTCAE criteria and reported accordingly Data Handling: Electronic data capture system compliant with ICH-GCP and CDISC standards Confidential storage at Xi'an Jiaotong University First Affiliated Hospital Data anonymized for reporting Ethics: Conducted in accordance with the Declaration of Helsinki and Chinese clinical research regulations Protocol approved by local ethics committee Written informed consent required before study enrollment Study Timeline: Planned start: June 2025 Planned completion: June 2028

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

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.

Treatment of Chidamide and Venetoclax for Retinoic Acid and Arsenic Resistant Acute Promyelocytic Leukemia

Based on the current treatment with retinoic acid (ATRA) and arsenic (As), most patients with APL achieved long-term survival. There are few patients relapsed and became refractory to the RA and As treatment. In our pre-clinical study, we found that targeting histone deacetylase inhibitor 3 (HDAC3)degraded PML-RARa oncoprotein and induced differentiation and apoptosis of RA and As resistant APL in vitro and in vivo. In this study, we evaluate the efficacy and feasibility of combination therapy for HDAC3 inhibitor and venetoclax in patients with refractory APL.