CX-01 in combination with standard chemotherapy for AML treatment – a phase I study

Therapy for acute myeloid leukemia (AML) is associated with pancytopenia and a high failure rate due to resistant leukemia stem cells that use CXCL12/CXCR4 axis to home to marrow niches. CX-01, a low anti-coagulant heparin, binds and inhibits platelet factor 4 (PF4 negatively regulates bone marrow recovery after chemotherapy and may also disrupt the CXCL12/CXCR4 axis), thus neutralizing its activity and improving the efficacy of AML therapy. 

In an article published in Blood Advances, Tibor J. Kovacsovics from Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, and colleagues reported results from a pilot phase I study (NCT02056782), which is evaluating the safety and preliminary efficacy of CX-01 in AML patients receiving standard chemotherapy.

In total, 12 AML patients with a median age of 56 years were enrolled in this study. Patients were administered induction therapy consisting of cytarabine (100 mg/m² as a continuous 24-hour infusion on Days 1–7) and idarubicin (12 mg/m² as a slow intravenous push on Days 1–3) along with CX-01 (bolus of 4 mg/kg over the course of 30 minutes immediately after the first dose of idarubicin, followed by a continuous infusion at 0.25 mg/kg per hour for 24 hours on Days 1–7).

Key findings

• Eleven (92%) patients achieved morphologic complete remission (CR) after one induction cycle
• Median time to a WBC count recovery of at least 13 x 10⁹ /L in evaluable patients (n = 8) was 21 days (mean, 23 ± 4.8; range, 20–35 days)
• Median time to recovery of an untransfused platelet count of at least 20 × 10⁹/L in evaluable patients (n = 10) was 21 days (mean, 21.3 ± 1.7; range, 18 –22)
• Median disease-free survival was 14.8 months
• Median overall survival was not reached at the maximum follow-up time of 29.4 months
• Serious adverse events occurred in five patients possibly unrelated to CX-01

The authors concluded by noting that the preliminary data from this phase I pilot study demonstrated that CX-01 in combination with standard chemotherapy was safe and well tolerated thus indicating its feasibility in the treatment of AML patients. Additionally, the preliminary data show promising CR rates and rapid platelet recovery. They, however, suggested that the findings of this study would require confirmation from a larger study which if confirmed would offer a valuable adjunctive therapy for AML patients.

In January 2018, CX-01 was granted Orphan Drug Designation status by the  U.S Food and Drug Administration (FDA).