Acute Promyelocytic Leukaemia, Acute Promyelocytic Leukemia, Acute Promyelocytic Leukemia (APL), Acute Promyelocytic Leukemia With PML-RARA, Acute Promyelocytic Leukemia With t(15;17)(q24.1;q21.2); PML-RARA
Conditions
Keywords
APL, Acute Promyelocytic Leukemia, Hematology, Oncology, Leukemia, Hematologic Disease, Drug Therapy, Therapeutics, Blood Cancer, Heme Malignancy, Arsenic, low-risk APL, standard-risk APL
Brief summary
This Phase 3 study in adult participants with newly diagnosed low-risk APL will evaluate the efficacy, safety, and PK of an oral capsule formulation of ATO, in combination with ATRA.
Interventions
DRUGQTX-2101 + ATRA
The experimental regimen consists of IV ATO administered once daily during induction, given continuously, for up to a maximum of 60 days. During consolidation, QTX-2101 is administered once daily, per investigator's protocol. ATRA is administered orally in two divided daily doses during induction, given continuously until bone marrow remission (not exceeding 60 days). During consolidation, ATRA is taken orally in two divided daily doses following a 2-weeks-on / 2-weeks-off schedule within each 8-week cycle.
DRUGIV arsenic trioxide (ATO) + ATRA
The comparator regimen consists of IV ATO administered once daily during induction, given continuously, for up to a maximum of 60 days. During consolidation, IV ATO is administered once daily, per investigator's protocol. ATRA is administered orally in two divided daily doses during induction, given continuously until bone marrow remission (not exceeding 60 days). During consolidation, ATRA is taken orally in two divided daily doses following a 2-weeks-on / 2-weeks-off schedule within each 8-week cycle.
Sponsors
Quetzal Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 71 Years
Healthy volunteers
No
Inclusion criteria
1. Informed Consent 2. Participants must be between 18 and under 71 years of age 3. Participants must have a confirmed diagnosis of APL proven by standard genetic testing (t(15;17) or PML-RARA) 4. Participants must be classified as low- or intermediate-risk APL 5. Participants must be willing and able to comply with the scheduled study visits, treatment plans, laboratory tests, contraception guidance, and other procedures
Exclusion criteria
1. Participants who have significant heart rhythm problems including long QT syndrome, serious arrhythmias, very slow heart rate, or prolonged QTc on ECG 2. Participants who have central nervous system leukemia 3. Participants having serious ongoing medical conditions or infections including uncontrolled infections, severe organ disease, or conditions that make study participation unsafe 4. Participants who are pregnant, breastfeeding, or unwilling to use contraception 5. Participants who are unable to safely take study medication, including severe neuropathy, inability to swallow oral medication, malabsorption issues, or known allergy to ATO or ATRA
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma (concentration (Cmax) of QTX-2101 for ASIII | Up to 1 cycle of consolidation therapy (each cycle is 8 weeks) | Cmax is defined as the maximum observed plasma concentration following administration of \[investigational product\], determined from plasma concentration-time data. |
| Molecular complete remission (molecular CR) rate | Up to 60 days of induction and 3 8-week cycles of consolidation treatment | mCR is defined as the absence of detectable PML-RARA fusion transcript in bone marrow assessed by a validated quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay .The mCR rate is defined as the proportion of participants achieving molecular remission at the specified assessment time point following induction and consolidation therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To characterize the safety and tolerability of QTX-2101/ATRA and IV ATO/ATRA | Throughout approximately 10 months of study treatment | Treatment emergent adverse events |
| To characterize the event-free survival (EFS) of QTX-2101/ATRA | Assessed for up to 3 years after the first dose of treatment, or until treatment failure (disease progression), death, or study completion, whichever occurs first | — |
| Area under the plasma concentration-time curve (AUC) of QTX-2101 for ASIII | Up to 10 months | AUC is defined as the area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC₀-t) and/or extrapolated to infinity (AUC₀-∞), calculated using noncompartmental methods. |
| To complete a model-based concentration QT relationship evaluation | Up to 10 months | Time-matched difference in change from baseline in QTcF interval between active treatment and placebo, derived from triplicate 12-lead ECGs at each post-dose time point |
| EORTC QLQ-C30 domain unit of measure and measurement tool | Up to 10 months | Change from baseline in EORTC QLQ-C30 global health status (0-100 scale) |
| EQ-5D-5L domain unit of measure and measurement tool | Up to 10 months | Change from baseline in EQ-5D-5L index score (0-100) |
| Overall Survival | Assessed for up to 3 years after the first dose of treatment, or until treatment failure (disease progression), death, or study completion, whichever occurs first | OS is defined as the time from randomization to death from any cause. Participants who are alive at the time of analysis will be censored at the date last known to be alive. |
| Event Free Survival (EFS) | Assessed for up to 3 years after the first dose of treatment, or until treatment failure (disease progression), death, or study completion, whichever occurs first | EFS is defined as the time from randomization to the first occurrence of any of the following events: failure to achieve hematologic or molecular remission, relapse (hematologic or molecular), or death from any cause. Participants without an event at the time of analysis will be censored at the date of last adequate disease assessment. |
Countries
France, Italy, Romania, Spain, United States
Outcome results
None listed