CX-01 Combination Associated With High Response Rate in Older Patients With AML

Treatment with CX-01 and standard chemotherapy induced high response rates – including complete responses (CRs) – in older patients newly diagnosed with acute myeloid leukemia (AML), according to results from a randomized, dose-finding study presented at the 2019 ASCO Annual Meeting.

CX-01 is a heparin derivative, explained lead author and presenter Tibor Kovacsovics, MD, from University of Utah Health in Salt Lake City. “It has no anticoagulant properties, but retains certain other functions of heparin, in particular its anti-inflammatory properties,” he said. These include blocking the activity of chemokines, such as CXCR4, CXCL12, and platelet factor 4, that promote treatment resistance and delay bone marrow recovery after chemotherapy.

The trial included 76 patients aged 60 years or older with previously untreated de novo or secondary AML. Eligible participants had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

Patients were randomized to receive induction therapy with either:

  • idarubicin and cytarabine on a 7+3 schedule alone (group 1)
  • idarubicin and cytarabine plus CX-01 0.125 mg/kg/hour (group 2)
  • idarubicin and cytarabine plus CX-01 0.25 mg/kg/hour (group 3)

In groups 2 and 3, CX-01 was given as a continuous infusion after a 4 mg/kg bolus until the completion of chemotherapy.

If patients achieved a CR, they received consolidation therapy consisting of up to three cycles of intermediate dose cytarabine (1,000 mg/m2 every 12 hours on days 1, 3, and 5). People in CR in groups 2 and 3 also received the same doses of CX-01.

In the entire population, 55% of participants had unfavorable-risk AML. Dr. Kovacsovics noted that there was an imbalance among the treatment groups in terms of disease risk, with 79% of patients in group 2 having unfavorable disease (compared with >40% in the other treatment groups).

At the time of data presentation, 65 patients were evaluable for response: 25/26 in group 1, 22/25 in group 2, and 18/24 in group 3. The most common cause of discontinuation was withdrawal of consent, while others discontinued when midostaurin was approved in April 2017. Also, one patient in group 2 died after development of hepatic sinusoidal obstructive disease at day 21 of treatment.

“We saw a high rate of dropout, mostly in the high-dose group,” Dr. Kovacsovics noted, which led the researchers to analyze outcomes among evaluable patients, rather than in the intent-to-treat population.

At the time of data cutoff, 58% of patients who received chemotherapy alone experienced a CR or CR with incomplete recovery (CRi), the study’s primary endpoint. However, in group 3, in which patients received the higher dose of CX-01, the CR/CRi rate was 89%. Interestingly, patients in group 2, who received a lower dose of CX-01, had a CR/CRi rate of 50%, which appeared to be lower than among patients in the chemotherapy-alone group.

Compared with treatment with chemotherapy alone, treatment with the higher dose of CX-01 also was associated with a statistically significant improvement in event-free survival (23.4 months in group 3 vs. 9 months in group 1; p=0.011) and overall survival (not reached vs. 11.2 months; p=0.042).

The adverse events observed in this study were similar to those seen in the earlier pilot trial, and “the toxicities were consistent with what is expected for aggressive AML therapy,” including seven cases of febrile neutropenia and three instances of respiratory failure, Dr. Kovacsovics said. Rates of mortality at 30 days, however, appeared to be highest in the high-dose CX-01 group (5.8% in group 1; 4% in group 2; 12.5% in group 3).

“The encouraging complete response rate and event-free survival in older, fit patients with newly diagnosed AML suggests that CX-01 may potentiate the efficacy of standard AML induction therapy,” the authors concluded.

The authors noted that this report includes results from evaluable patients, and not the intent-to-treat population, which is a potential limitation of this analysis.

The authors report relationships with Cantex Pharmaceuticals, which sponsored the trial.


Kovacsovics T, Levy MY, Cook RJ. A randomized phase II trial of CX-01 with standard therapy in elderly patients with acute myeloid leukemia (AML). Abstract #7001. Presented at the 2019 ASCO Annual Meeting, June 1, 2019; Chicago, IL.