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Trial record 1 of 1 for:    NCT02658487
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Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia (VITAL)

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ClinicalTrials.gov Identifier: NCT02658487
Recruitment Status : Active, not recruiting
First Posted : January 18, 2016
Last Update Posted : May 24, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Stephen Strickland, Vanderbilt-Ingram Cancer Center

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia 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 Drug: Cytarabine Drug: Vosaroxin Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the rate of complete remission (CR) after induction therapy with the combination of "7+V" (vosaroxin and standard dose infusional cytosine arabinoside [ara-C]) for patients with newly diagnosed, previously untreated acute myelogenous leukemia (AML).

SECONDARY OBJECTIVES:

I. Frequency of grade 3-5 adverse events related to administration of "7+V".

II. To evaluate for the presence of minimal residual disease (MRD) remaining after "7+V" induction and/or re-induction.

III. To determine the CR/CR with incomplete blood count recovery (CRi) rate after one and/or 2 cycles of "7+V" induction.

IV. To determine the time to neutrophil and platelet recovery following "7+V" induction.

V. To assess disease-free survival (DFS) at 1 year (yr) of patients achieving CR/CRi after "7+V" induction.

VI. To assess overall survival (OS) at 1 yr of all patients receiving protocol-defined therapy.

VII. To determine the correlation of hematopoietic stem cell transplant (HSCT) comorbidity index and Wheatley Index scores with disease response, DFS and OS.

TERTIARY OBJECTIVES:

  • I. To describe the mutational burden of this cohort of AML patients.
  • II. To correlate genomic aberration with response rate, DFS, and OS.
  • III. To determine the number of patients treated with vosaroxin who eventually go to allogeneic HSCT.

OUTLINE:

Patients receive vosaroxin intravenously (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-1

After completion of study treatment, patients are followed every 3 months for 1 year.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 61 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Vosaroxin in Combination With Infusional Cytarabine in Patients With Untreated AML
Study Start Date : March 2016
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : July 2020


Arm Intervention/treatment
Experimental: Treatment (vosaroxin, cytarabine)
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
Given IV
Other Names:
  • .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

Drug: Vosaroxin
Given IV
Other Names:
  • AG-7352
  • SNS-595
  • SPC 595
  • Voreloxin




Primary Outcome Measures :
  1. Complete remission rate (CR) [ Time Frame: Up to 3 months ]
    A likelihood ratio, not a tail area probability (p-value), will be used to represent the strength of statistical evidence with respect to either a 40% or 60% true CR rate. It is assumed the complete remission rate of standard induction chemotherapy is 40% in the targeted population of this trial and that the use of vosaroxin in combination with cytarabine may increase this rate to 60%.


Secondary Outcome Measures :
  1. Event-free survival [ Time Frame: The time from start of therapy to progression or death for any reason, assessed up to 1 year ]
    Survival distribution will be estimated using the method of Kaplan and Meier and comparison of the distribution among patient subgroups will be made using the logrank test. Multivariable models of response and survival estimates will be constructed using logistic and Cox (proportional hazards) regression.

  2. Frequency of grade 3-5 adverse event related to Cytarabine and Vosaroxin (7+V) [ Time Frame: Up to day 3 months ]
    Events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Frequency and percentage of patients will be summarized for any adverse event by grade, attribution, organ class, and preferred term overall and by patient. Change in continuous laboratory data from just prior to therapy and by visit will be summarized by frequency of abnormal values. Linear and non-linear regression will be used to model changes over time, accounting for intra-patient correlation using mixed models or generalized estimating equation, as appropriate.

  3. Leukemia-free survival (LFS or DFS) [ Time Frame: The time from complete remission to disease progression or death for any reason, assessed up to 1 year ]
    Survival distribution will be estimated using the method of Kaplan and Meier and comparison of the distribution among patient subgroups will be made using the logrank test. Multivariable models of response and survival estimates will be constructed using logistic and Cox (proportional hazards) regression. Time to response will be implemented as a time-dependent covariate in models assessing LFS.

  4. Overall Survival [ Time Frame: The time from start of therapy to death for any reason, assessed up to 1 year ]
    Survival distribution will be estimated using the method of Kaplan and Meier and comparison of the distribution among patient subgroups will be made using the logrank test. Multivariable models of response and survival estimates will be constructed using logistic and Cox (proportional hazards) regression.

  5. Minimal Residual Disease [ Time Frame: Up to 3 months ]
    Frequency of minimal residual disease (MRD) remaining after "7+V" induction and/or re-induction

  6. Rate of Complete Remission / Complete Remission with Incomplete Count Recovery (CR/CRi) [ Time Frame: Up to 3 months ]
    Frequency of CR/CRi after "7+V" induction and/or re-induction


Other Outcome Measures:
  1. Correlate HSCT comorbidity index, Wheatley Index, and AML-Score values with disease response [ Time Frame: Up to 3 months ]
  2. Correlate HSCT comorbidity index, Wheatley Index, and AML-Score values with DFS [ Time Frame: The time from complete remission to disease progression or death for any reason, assessed up to 1 year ]
  3. Correlate HSCT comorbidity index, Wheatley Index, and AML-Score values with OS [ Time Frame: The time from start of therapy to death for any reason, assessed up to 1 year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 FLT3-ITD
    • Myeloid sarcoma
    • AML with multilineage dysplasia (AML-MLD)
    • Adverse cytogenetics (defined as -5/-5q; -7/-7q; abnormal 3q, 9q, 11q, 20q, 21q or 17p; t(6;9); t(9;22); trisomy 8; trisomy 13; trisomy 21; complex karyotypes (>= 3 clonal abnormalities); monosomal karyotypes
  • FOR PATIENTS IN STAGE 2 (ENROLLED PATIENT #18 AND BEYOND)
  • >= 55 years of age with AML of any risk classification, or 18-54 years of age with intermediate or high risk AML as defined by National Comprehensive Cancer Network (NCCN) risk assignment

Exclusion Criteria:

  • 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:

    • Hydroxyurea or medications to reduce blast count within 24 hours before randomization
    • Treatment with an investigational product within 14 days before randomization, or not recovered from all acute effects of previously administered investigational products
  • Renal insufficiency requiring hemodialysis or peritoneal dialysis
  • Pregnant or breastfeeding
  • Known human immunodeficiency virus (HIV) seropositivity
  • Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator or medical monitor
  • ADDITIONAL EXCLUSION CRITERIA APPLIED TO STAGE 1
  • Patients 18-54 years of age with "good risk" AML defined as the presence of t(8;21), inv(16), or t(16;16) as diagnosed by morphologic criteria, flow cytometric characteristics, and rapid cytogenetics or FISH
  • Patients with t(8;21), inv(16), t(16;16) who are unable to receive anthracycline based induction will be allowed to enroll provided the medical reason they are unable to receive anthracyclines is clearly documented and provided they fulfill all other eligibility and criteria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02658487


Locations
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United States, California
University of California-Los Angeles
Los Angeles, California, United States, 90024
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, South Carolina
Medical University of South Carolina Hollings Cancer Center
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Stephen Strickland, MD Vanderbilt-Ingram Cancer Center
Principal Investigator: Michael Savona, MD Vanderbilt-Ingram Cancer Center

Additional Information:
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Responsible Party: Stephen Strickland, Assistant Professor of Medicine, Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT02658487     History of Changes
Other Study ID Numbers: VICC HEM 1553
NCI-2015-01735 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA068485 ( U.S. NIH Grant/Contract )
First Posted: January 18, 2016    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
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Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Sarcoma, Myeloid
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Sarcoma
Neoplasms, Connective and Soft Tissue
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs