West Virginia University Continues Follow-up on New AML Combination Phase 1 Trial with Asparlas
Dose-Exploration Study with 6 Participants
NCT04953780, led by West Virginia University, is an open-label, non-randomized Phase 1 clinical trial evaluating the combination of Asparlas (pegaspargase-mknl) with high-dose cytarabine and idarubicin in adult patients with newly diagnosed acute myeloid leukemia (AML). The trial began in September 2021, enrolled 6 actual participants, and recruitment ended in March 2025 with ongoing follow-up. The primary objective is to determine regimen-limiting toxicity (RLT), maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D), focusing on assessing the feasibility of further development rather than confirming efficacy.
Asparagine Depletion Applied to AML
Asparlas, marketed by Servier, is a pegylated L-asparaginase with the active ingredient pegaspargase-mknl. It depletes asparagine in the blood, blocking the supply of this amino acid necessary for protein synthesis. Cytosar-U (cytarabine) inhibits DNA polymerase and DNA synthesis, while Idamycin PFS (idarubicin) inhibits topoisomerase II, applying complementary pressure to leukemia cells. The study's differentiator is the extension of asparaginase use from acute lymphoblastic leukemia (ALL) to AML, but safety margins in adult AML must first be established.
High-Intensity Induction and Consolidation Regimen
The induction regimen involves six doses of cytarabine 3000 mg/m², three doses of idarubicin 12 mg/m², followed by pegaspargase-mknl 750–2000 U/m² in a dose-escalation structure. Patients achieving remission receive up to four cycles of consolidation therapy combining high-dose cytarabine and pegaspargase-mknl. Secondary endpoints include complete remission (CR), complete remission with partial hematologic recovery (CRh), and complete remission with incomplete hematologic recovery (CRi). However, the small sample size of 6 participants is insufficient to determine comparative efficacy or survival improvements.
Regulatory and Competitive Landscape
The FDA approved Asparlas as a component of multi-drug therapy for ALL patients aged 1 month to 21 years on December 20, 2018, but has not approved it for adult AML indications. The current standard treatment options for new AML include 7+3 (cytarabine and anthracycline) for fit patients, venetoclax (BCL2 inhibitor) with azacitidine for unfit patients, and quizartinib (FLT3 inhibitor) in combination for FLT3-ITD positive patients. The global AML treatment market is estimated to reach USD 3.91 billion in 2025, but for this study to gain commercial competitiveness, larger comparative trials are needed after establishing toxicity management and RP2D.
Since this is a Phase 1 trial with only 6 enrolled patients, short-term investment value is primarily determined by whether regimen-limiting toxicity, maximum tolerated dose, and recommended Phase 2 dose can be derived. Asparlas is a repurposing strategy of an FDA-approved and marketed ALL treatment for AML, so initial manufacturing and regulatory foundations are in place, but the key risk is whether its toxicity profile overlaps with high-intensity chemotherapy, particularly pancreatitis, thrombosis, bleeding, and hepatotoxicity. For researchers, this small-scale human data will verify whether asparagine depletion can achieve pharmacodynamic effects in AML and lead to CR, CRh, or CRi. The industry is already forming treatment paradigms around 7+3, AbbVie's venetoclax combination, and Daiichi Sankyo's quizartinib, making differentiation barriers high. Until Phase 2 progression and remission and survival data with a control group are secured, a Watchlist approach is appropriate for investment decisions.
Source: ClinicalTrials.gov (api_ct)