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

NCT02995655 · Status: COMPLETED · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 20

Last updated 2019-12-05

No results posted yet for this study

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

Interventions

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

Sponsors & Collaborators

  • Cantex Pharmaceuticals

    collaborator INDUSTRY

  • Washington University School of Medicine

    lead OTHER

Principal Investigators

  • Peter Westervelt, M.D., Ph.D. · Washington University School of Medicine

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2017-04-07
Primary Completion
2018-09-13
Completion
2019-04-29
FDA Drug
Yes

Countries

  • United States

Study Locations

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Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02995655 on ClinicalTrials.gov