Clinical trial NCT01913951: Vosaroxin and Azacitidine in Treating Patients With Myelodysplastic Syndromes
Official title: A Phase I Study of Vosaroxin Plus Azacitidine for Patients With Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Myelodysplastic Syndromes
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Sunesis Pharmaceuticals
First posted: 2013-08-01
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: MTD of vosaroxin in combination with azacitidine
timeFrame: 28 days
Secondary outcomes:
measure: Best response (including hematologic improvement)
timeFrame: At 3 cycles
measure: Best overall response
timeFrame: Up to 7 months
measure: Incidence of adverse events
timeFrame: Up to 7 months
measure: Time to response
timeFrame: Up to 7 months
measure: Event-free survival
timeFrame: up to 5 years
measure: Progression-free survival (PFS)
timeFrame: up to 5 years
measure: Disease-free survival (DFS)
timeFrame: up to 5 years
measure: Overall survival (OS)
timeFrame: up to 5 years
measure: Biomarkers of response to vosaroxin and azacitidine therapy
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Meagan Jacoby, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.