Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia

NCT02658487 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: VICC HEM 1553NCI-2015-01735P30CA068485
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial studies how well vosaroxin and cytarabine work in treating patients with untreated acute myeloid leukemia. Drugs used in chemotherapy, such as vosaroxin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Conditions

Acute Myeloid Leukemia (AML); Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia With Multilineage Dysplasia; Myeloid Sarcoma; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Therapy-Related Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Complete Remission Rate (CR)

  CR is calculated as the percentage of patients with complete remission after the therapy. The response criteria is based on International Working Group Criteria. Complete Remission: Neutrophils(cells/μl)\>1000, Platelets (plt/μl)≥ 100,000,Bone marrow blasts (%) \<5; CR with incomplete count recovery (CRi): meets criteria for CR except for neutrophils ≤1000 or Meets criteria for CR except for platelets\< 100,000; Partial Remission: CR except for Bone marrow blasts (%) Decrease of ≥ 50% to value between 5% and 25%; Treatment Failure:Persistent acute myeloid leukemia in blood or bone marrow, or therapy fails to achieve a remission of any category, or death prior to response assessment

  Up to 3 months

Secondary Outcomes (6)

• Event-free Survival

  From start of therapy up to 1 year

• Frequency of Grade 3-5 Adverse Event Related to Cytarabine and Vosaroxin (7+V)

  Up to 3 months

• Leukemia-free Survival (LFS or DFS)

  The time from complete remission to disease progression or death for any reason, assessed up to 1 year

• Overall Survival

  The time from start of therapy to death, assessed up to 1 year

• Minimal Residual Disease

  Up to 3 months

Other Outcomes (3)

• Correlation of Three Standard Prognostic Scores of AML Risk With Disease Response

  Up to 3 months

• Correlate HSCT Comorbidity Index, Wheatley Index, and AML-Score Values With DFS

  The time from complete remission to disease progression or death for any reason, assessed up to 1 year

• Correlation of Standard Prognostic Scores of AML Risk With Survival

  The time from start of therapy to death for any reason, assessed up to 1 year

Study Arms (1)

Treatment (vosaroxin, cytarabine)

EXPERIMENTAL

Patients receive vosaroxin IV on days 1 and 4 and cytarabine IV continuously on days 1-7 (Induction I). Patients with residual leukemia and for whom a second course is indicated in the judgment of the investigator may undergo a second course of treatment (Induction II) 14-57 days after day 1 of Induction I.

Drug: Cytarabine; Drug: Vosaroxin

Interventions

Cytarabine DRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (vosaroxin, cytarabine)

Vosaroxin DRUG

Given IV

Also known as: AG-7352, SNS-595, SPC 595, Voreloxin

Treatment (vosaroxin, cytarabine)

Eligibility Criteria

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

You may qualify if:

• Ability to provide informed consent
• Ability to tolerate intensive therapy with vosaroxin 90 mg/m\^2 and cytarabine
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 at time of study entry
• Morphologically confirmed new diagnosis of AML in accordance with World Health Organization (WHO) diagnostic criteria
• Patients who have received hydroxyurea alone or have previously received "non-cytotoxic" therapies for myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN) (e.g., thalidomide or lenalidomide, 5-azacytidine or decitabine, histone deacetylase inhibitors, low-dose Cytoxan, tyrosine kinase or dual tyrosine kinase \[TK\]/SRC proto-oncogene, non-receptor tyrosine kinase \[src\] inhibitors) will be allowed
• Serum creatinine =\< 2.0 mg/dL
• Hepatic enzymes (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\]) =\< 2.5 x upper limit of normal
• Total bilirubin =\< 1.5 x upper limit of normal unless clearly related to Gilbert's disease, hemolysis or leukemic infiltrate
• FOR PATIENTS IN STAGE 1 (PATIENTS #1-#17)
• \>= 55 years of age with AML of any risk classification, or 18-54 years of age with high-risk AML disease based on one of the following:
• Antecedent hematologic disorder including myelodysplasia (MDS)-related AML (MDS/AML) and prior myeloproliferative disorder (MPD)
• Treatment-related myeloid neoplasms (t-AML/t-MDS)
• AML with FMS-like tyrosine kinase 3 (FLT3) - internal tandem duplication (ITD)
• Myeloid sarcoma
• AML with multilineage dysplasia (AML-MLD)

You may not qualify if:

• STAGES 1 AND 2
• Patients with acute promyelocytic leukemia (APL) as diagnosed by morphologic criteria, flow cytometric characteristics, and rapid cytogenetics or fluorescence in situ hybridization (FISH) or molecular testing
• Any previous treatment with vosaroxin
• Concomitant chemotherapy, radiation therapy
• For patients with hyperleukocytosis with \> 50,000 blasts/μL; leukapheresis or hydroxyurea may be used prior to study drug administration for cytoreduction at the discretion of the treating physician
• Active, uncontrolled infection
• Patients with infection under active treatment and controlled with antibiotics, antivirals, or antifungals are eligible
• Chronic hepatitis is acceptable
• Active, uncontrolled graft vs. host disease (GVHD) following allogeneic transplant for non-AML condition (e.g. MDS, lymphoid malignancy, aplastic anemia); patients with GVHD controlled on stable doses of immunosuppressants are eligible
• Presence of other life-threatening illness
• Left ventricular ejection fraction (LVEF) \< 40% as measured by echocardiogram or multi gated acquisition scan (MUGA)
• Known or suspected central nervous system (CNS) involvement of active AML
• Other active malignancies including other hematologic malignancies or other malignancies within 12 months before randomization, except nonmelanoma skin cancer or cervical intraepithelial neoplasia
• History of myocardial infarction (MI), unstable angina, cerebrovascular accident, or transient ischemic attack (CVA/TIA) within 3 months before randomization
• Prior or current therapy:

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Yale University

New Haven, Connecticut, 06520, United States

Location

Medical University of South Carolina Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Related Links

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Sarcoma, Myeloid

Interventions

Cytarabine; vosaroxin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Sarcoma; Neoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Stephen Strickland, MD
• Organization: Vanderbilt University Medical Center

stephen.strickland@vumc.org

(615) 936-8422

Study Officials

• Sanjay Mohan, MD

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

• Michael Savona, MD

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine, Division of Hematology/Oncology

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: January 18, 2016
• Study Start: March 1, 2016
• Primary Completion: April 1, 2019
• Study Completion: September 1, 2024
• Last Updated: April 15, 2025
• Results First Posted: June 9, 2020

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)