CX-01 Heparin Derivative Investigated for Older Patients With AML


A randomized phase II trial investigated whether adding CX-01, a low anticoagulant heparin derivative, to standard care improves outcomes in older patients with acute myeloid leukemia.

A new randomized phase II trial suggests that adding CX-01, a low anticoagulant heparin derivative, to standard care may help improve outcomes in older patients with acute myeloid leukemia (AML). The researchers, who presented the findings (abstract 7001) at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, report that a randomized study is warranted to confirm these findings with the higher dose of CX-01.

“After decades in which multiple studies failed to demonstrate incremental improvement over 7 + 3 as standard of care induction chemotherapy for AML, it has been exciting to finally witness potential progress in this area, which these results certainly suggest,” said study investigator Peter Westervelt, MD, PhD, who is an associate professor of medicine and chief of Bone Marrow Transplantation at Washington University’s Siteman Cancer Center in St. Louis.

Westervelt and colleagues note that older patients with AML patients tend to have poor outcomes regardless of treatment regimen. This new agent, CX-01, is a polysaccharide that retains heparin’s ability to alter the activity of the CXCL12/CXCR4 axis, P-selectin, extracellular histones, and Platelet Factor. Part of a class of compounds known as heparinoids, these agents possess biologic and therapeutic properties separate from their use as anticoagulants. A previous study showed that CX-01 combined with standard therapy for AML led to a complete remission (CR) rate of 92%.

For this current investigation, researchers conducted a randomized, dose-finding study with 76 fit patients who were older than age 59 years. They were randomized to one of three arms: induction with idarubicin and cytarabine on a 7+3 schedule only; 7+3 with a lower dose of CX-01 (0.125 mg/kg/hour); or 7+3 with a higher dose of CX-01 (0.25 mg/kg/hour). Patients who achieved a CR received consolidation therapy consisting of up to 3 cycles of intermediate-dose cytarabine with or without the same dose of CX-01.

The researchers presented results on 66 of 75 evaluable patients and not on an intent-to-treat basis. They found that composite CR rate (CR + CRi) was highest in patients receiving the higher dose, with 89% achieving a composite CR compared with 58% in Group 1 and 50% in Group 2 (lower dose). The researchers found there was a statistically significant improvement in event-free survival (EFS) (P = .019) and a non-significant trend (P = .10) to improvement in OS in the high-dose group compared with Group 1.

The study showed no significant differences between Groups 1 and 2 for EFS and OS. CX-01 appeared to be well tolerated with no significant increased incidence of bleeding in either group receiving CX-01. “At our site, we did not witness significant toxicity apart from that expected with chemotherapy itself in this population,” Westervelt told Cancer Network.

Richard J. Jones, MD, professor of oncology and medicine and director of the Bone Marrow Transplantation Program at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, said this study must be viewed with caution because the patient sample size is so small and AML is a very heterogeneous disease. “Small differences in risk-type of AML among arms could greatly skew results with such small numbers,” Jones told Cancer Network.

Jones added that this study group presented results for evaluable patients and not on an intent-to-treat basis, which may be another reason to interpret these findings cautiously. CX-01 is currently in clinical development for refractory AML and myelodysplastic syndrome (MDS). Among its biologic activities, CX-01 is designed to block the activity of chemokines, which support the resistance of blood cancers to treatment and contribute to the delay of bone marrow recovery after chemotherapy.

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