NCT02995655

CX-01 Combined With Azacitidine in the Treatment of Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia

A Pilot Study of CX-01 Combined With Azacitidine in the Treatment of Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The investigators hypothesize that CX-01 will disrupt the bone marrow microenvironment and increase the cytotoxic effects of azacitidine on myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) hematopoietic stem cells by disrupting the High-mobility group box protein 1 (HMGB1) interaction with toll-like receptor 4 (TLR4) and receptors for advanced glycation end products (RAGE), the CXC chemokine CXCL12/chemokine receptor 4 (CXCR4) axis, and by disrupting other leukocyte and vascular adhesion molecules. In addition, CX-01 may also help promote count recovery after treatment given its affinity for platelet factor-4 (PF4). The selection of CX-01 dose for study in relapsed or refractory MDS and AML has been based upon the dual requirements to have sufficient drug administered to have potential activity but without clinically significant anticoagulation. The study dose chosen (4 mg/kg bolus followed by 0.25 mg/kg/hour) fulfills both of these criteria. In addition, this dose is expected to result in serum levels of CX-01 which are significantly higher than the IC90 identified in preclinical studies for inhibition of HMGB1-RAGE, toll-like receptor 2 (TLR2) and TLR4 interaction. Therefore, the chosen dose represents a rational balance between effective dosing and safety in thrombocytopenic patients with MDS and AML. This dose was previously established to be safe and tolerable when combined with cytarabine and idarubicin in patients with AML.

Conditions

• Myelodysplastic Syndromes
• Acute Myeloid Leukemia
• AML
• MDS

Interventions

Type	Name	Description
DRUG	CX-01	CX-01 at a dose of 4mg/kg on Day 1 of each 28-day cycle, followed by a continuous intravenous infusion at a dose of 0.25 mg/kg/hour for Days 1 through 7 of each cycle.
DRUG	Azacitidine	Azacitidine at a dose of 75mg/m\^2 on Days 1-7 of each 28-day cycle.
PROCEDURE	Bone marrow biopsy	-Baseline, day 28 of even-numbered cycle through Cycle 6, and end of study
PROCEDURE	Peripheral blood draw	-Day 1 of each cycle, day 3 of each cycle, day 7 of each cycle, day 28 of every even-numbered cycle through Cycle 6, and end of study

Timeline

• Start date: 2017-04-07
• Primary completion: 2018-09-13
• Completion: 2019-04-29
• First posted: 2016-12-16
• Last updated: 2019-12-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study