The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Older patients with AML tend to have poor outcomes regardless of the kind of therapy they receive. But 1 study showed that administering a combination of the low-anticoagulant heparin derivative CX-01 and standard therapy for AML resulted in a complete remission rate of 92%.1 Now, researchers have conducted a randomized, dose-finding study of the same drug in newly diagnosed patients with the condition, which also yielded promising results according to data presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.2

The new findings suggest that CX-01 may strengthen the efficacy of standard AML induction, the authors noted.

In the study, researchers randomly assigned 75 fit patients with AML who were older than 59 years to one of 3 groups; those in the first group, which acted as the control group, were induced with idarubicin and cytarabine on a 7+3 schedule only; those in the second group also received standard AML induction therapy on the same schedule as the first group but with a dose of 0.125 mg/kg/hour c; and those in the third group received standard AML induction therapy on the same schedule with a higher dose of CX-01 of 0.25 mg/kg/hour. People in complete remission were given consolidation therapy of up to 3 cycles of intermediate dose cytarabine, without or with the same lower or higher dose of CX-01 as above.

The researchers were able to evaluate 65 of all treated patients for response, because 6  patients withdrew consent, 3 patients received midostaurin after it was approved, and 1 patient in the group that received AML induction with the lower dose CX-01 died due to hepatic sinusoidal obstructive disease at Day 21.

The composite complete remission rate — including complete remission and complete remission with incomplete hematologic recovery — was highest among patients who received standard AML induction therapy with the higher dose of CX-01; in the higher-dose group, 89% of patients achieved a composite complete remission compared with 58% in the group that received standard AML induction therapy only and 50% in the group that received standard induction therapy with the lower dose of CX-01.

The researchers also found a statistically significant improvement in event free survival (P =.019) and a nonsignificant (P =.10) trend to improvement in overall survival in the group that received standard AML induction therapy and the higher dose of CX-01 compared with the group that received standard AML induction therapy alone. Event-free survival and overall survival were similar in the group that received standard induction therapy alone and the group that received standard induction therapy with the lower dose of CX-01.

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Both groups that received CX-01 tolerated it well, and did not have increased incidence of bleeding, according to the abstract — although it should be noted that the presenter did not discuss bleeding during the talk. The most common serious adverse events found in the study were febrile neutropenia and respiratory failure. Specifically, there were 7 cases of febrile neutropenia, including 3 cases in each CX-01 group and 1 case in the control group; there were 3 total cases of respiratory failure including 2 cases in the CX-01 groups and 1 case in the control group.

“CX-01 was really well tolerated,” said lead study author Tibor Kovacsovics, a professor in the department of internal medicine at the University of Utah in Salt Lake City. “The serious adverse event and adverse event rate was similar across all 3 treatment arms.”

The researchers also found that 30-day mortality was 12.5% in the high-dose CX-01 group, 5.8% in the control group, and 4.0% in the low-dose CX-01 group. Moreover, 60-day mortality was 12.5% in the high-dose group, 11.5% in the control group and 8.0% in the low-dose group.

A randomized study with the higher dose of CX-01 should be conducted to confirm these findings, the authors noted.

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.

References

  1. Kovacsovics T, Mims A, Salama ME, et al. Combination of the low anticoagulant heparin CX-01 with chemotherapy for the treatment of acute myeloid leukemia. Blood Adv. 2018;2(4):381-389.
  2. Kovacsovics T, Levy MY, Cook RJ, et al. A randomized phase II trial of CX-01 with standard therapy in elderly patients with acute myeloid leukemia (AML). Presented at: 2019 American Society of Clinical Oncology ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 7001.