Vosaroxin and Azacitidine in Treating Patients With Myelodysplastic Syndromes

NCT01913951 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 201309091
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and the best dose of vosaroxin when given together with azacitidine in treating patients with myelodysplastic syndromes. Drugs used in chemotherapy, such as vosaroxin and azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Conditions

Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• MTD of vosaroxin in combination with azacitidine

  Defined as the highest dose of vosaroxin that results in a DLT in =\< 1 of 6 patients graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0

  28 days

Secondary Outcomes (9)

• Best response (including hematologic improvement)

  At 3 cycles

• Best overall response

  Up to 7 months

• Incidence of adverse events

  Up to 7 months

• Time to response

  Up to 7 months

• Event-free survival

  up to 5 years

Study Arms (1)

Treatment (vosaroxin, azacitidine)

EXPERIMENTAL

Patients receive vosaroxin IV over 10 minutes on days 1 and 4 and azacitidine SC or IV over 15 minutes on days 1-7. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Drug: vosaroxin; Drug: Azacitidine

Interventions

vosaroxin DRUG

Given IV over 10 minutes on Day 1 and 4

Also known as: voreloxin

Treatment (vosaroxin, azacitidine)

Azacitidine DRUG

Given SC or IV over 15 minutes on days 1-7

Also known as: Vidaza, Ladakamycin

Treatment (vosaroxin, azacitidine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of myelodysplastic syndrome and one of the following:
• Cytopenias requiring red blood cell and/or platelet transfusions or neutropenia (ANC \<1 X109/L)
• IPSS score of INT-1 or higher at screening
• MDS with excess blasts in transformation as defined by FAB criteria (20-29% bone marrow blasts) or
• Chronic myelomonocytic leukemia
• Age ≥18 years old
• Adequate renal and hepatic function defined as all of the following:
• total bilirubin ≤ 2.0 mg/dl, except in cases of Gilbert's disease;
• AST and ALT ≤2.5 institutional ULN;
• serum creatinine within normal institutional limits or estimated creatinine clearance ≥60 mL/min/1.73 m2 by the Cockcroft-Gault equation
• ECOG performance status ≤2
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
• Females must be surgically or biologically sterile or postmenopausal or if of childbearing potential, must agree to use an adequate method of contraception during the study until 30 days after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 30 days after the last treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Patients may have received up to 3 prior cycles of hypomethylator therapy (i.e. decitabine or azacitidine) prior to enrollment and may have received supportive care measures (growth factors, erythropoietin stimulating agents, transfusion, etc.
• Either enrolled in HRPO# 201011766 ("Tissue Acquisition for Analysis of Genetic Progression Factors in Hematologic Diseases"), which facilitates collection of blood, bone marrow, and skin for correlative studies, or consents to collection of blood, bone marrow, and skin as part of this protocol.

You may not qualify if:

• Prior treatment with four or more cycles of hypomethylator therapy.
• Receiving concomitant chemotherapy, radiation therapy, or immunotherapy during the duration of treatment on protocol.
• Known seropositivity for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible. Patients who are seropositive for HCV, but have a negative viral load are also eligible. Documentation that the patients have completed a course of therapy for HCV is required and will be obtained.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant and/or breastfeeding.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Sunesis Pharmaceuticals: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Lancet JE, Ravandi F, Ricklis RM, Cripe LD, Kantarjian HM, Giles FJ, List AF, Chen T, Allen RS, Fox JA, Michelson GC, Karp JE. A phase Ib study of vosaroxin, an anticancer quinolone derivative, in patients with relapsed or refractory acute leukemia. Leukemia. 2011 Dec;25(12):1808-14. doi: 10.1038/leu.2011.157. Epub 2011 Jul 15.

  PMID: 21760592 BACKGROUND

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

vosaroxin; Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Meagan Jacoby, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2013
• First Posted: August 1, 2013
• Study Start: November 22, 2013
• Primary Completion: December 5, 2016
• Study Completion: April 29, 2024
• Last Updated: May 2, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)