Study of Vosaroxin With Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome With Excess Blasts-2

NCT03338348 | Completed Phase 2 DMC

• 1 other identifier: AMLSG 24-15
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

Brief Summary

The main part of this trial is a phase II study of vosaroxin with azacitidine in older patients with newly diagnosed AML and intermediate or adverse genetic risk or MDS-EB-2. An initial safety run-in phase of the study will be performed administering the study drug vosaroxin with azacitidine in up to 18 patients. After completion of the run-in phase, toxicity and response data will be provided to the external Data and Safety Monitoring Board (DSMB) and the Trial Committee by the Coordinating Investigator. The Trial Committee will decide on the basis of these data and the recommendation of the DSMB on dose modification and the vosaroxin dose for the phase II part of the study, which will include 150 patients in total.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome With Excess Blasts-2 (MDS-EB-2)

Keywords

Vosaroxin

Outcome Measures

Primary Outcomes (1)

• Rate of complete remission (CR) and CR with incomplete blood count recovery (CRi)

  Efficacy assessments

  2 months

Secondary Outcomes (8)

• CR and CRi in a pre-defined subgroup analysis in patients with complex karyotype

  2 months

• CR and rate of combined CR/CRi and CR with negativity for minimal residual disease (CRMRD-)

  2 months

• Duration of response (DOR)

  4 years

• Event-free survival (EFS)

  4 years

• Overall survival (OS)

  4 years

Study Arms (1)

Azacitidine + Vosaroxin

OTHER

Cycle 1-8: Azacitidine: 75 mg/m²/d subcutaneously, d 1-7; Vosaroxin: Dose Level 0: 70mg/m², Dose Level -1: 50mg/m², Dose Level -2: 40mg/m², IV over ten minutes, d 1+4 . Patients who have completed 8 cycles of azacitidine and vosaroxin are scheduled to maintenance with single agent azacitidine at 75 mg/m²/d on days 1-7 until relapse or progression.

Drug: Vosaroxin; Drug: Azacitidine

Interventions

Vosaroxin DRUG

Cycle 1-8: Dose Level 0: 70mg/m², Dose Level -1: 50mg/m², Dose Level -2: 40mg/m², IV over ten minutes, d 1+4 .

Azacitidine + Vosaroxin

Azacitidine DRUG

Cycle 1-8 Azacitidine: 75 mg/m²/d subcutaneously, d 1-7; Maintenance with single agent azacitidine at 75 mg/m²/d on days 1-7 until relapse or progression.

Azacitidine + Vosaroxin

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with confirmed diagnosis of acute myeloid leukemia (WHO 2016) and intermediate or adverse genetic risk (according to 2017 ELN recommendations); or patients with myelodysplastic syndrome with excess blasts-2 (MDS-EB-2)
• Patients ≥60 years of age
• No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis for up to 10 days during the diagnostic screening phase; patients may have received prior therapy for myelodysplastic syndrome different from hypomethylating agents
• ECOG performance status ≤2
• Men must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy and must agree to avoid to father a child (while on therapy and for 3 month after the last dose of vosaroxin)
• Non-pregnant and non-nursing women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to registration ("Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months).
• Female patients of reproductive age must agree to avoid getting pregnant while on therapy and for 3 months after the last dose of vosaroxin.
• Women of child-bearing potential including the female partners of the male patients must either commit to continued abstinence from heterosexual intercourse or apply two acceptable methods of birth control (IUD, tubal ligation, or partner's vasectomy). Hormonal contraception is an inadequate method of birth control.
• Men must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy (while on therapy and for three months after the last dose of chemotherapy)
• Willing to adhere to protocol specific requirements
• Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out

You may not qualify if:

• Known or suspected hypersensitivity to the study drugs and/or any excipients
• Favorable genetics: t(15;17)(q22;q12), PML-RARA; t(8;21)(q22;q22), RUNX1-RUNX1T1; inv(16)(p13.1q22)/t(16;16)(p13.1;q22), CBFB-MYH11; mutated NPM1 without FLT3-ITD or with FLT3-ITDlow
• Prior treatment for AML except hydroxyurea
• Prior treatment for MDS with hypomethylating agents
• ECOG performance status \>2
• Patients who are not eligible for intensive chemotherapy
• Inadequate cardiac, hepatic and/or renal function at the Screening Visit defined as:
• Ejection fraction \<40% confirmed by echocardiography
• Creatinine \>1.5x upper normal serum level
• Total bilirubin, AST or ALT \>1.5 upper normal serum level
• Active central nervous system involvement
• Any clinically significant, advanced or unstable disease or history of that may interfere with primary or secondary variable evaluations or put the patient at special risk, such as:
• Myocardial infarction, unstable angina within 3 months before screening
• Heart failure NYHA III/IV
• Severe obstructive or restrictive ventilation disorder

Sponsors & Collaborators

• University of Ulm: lead
• Sunesis Pharmaceuticals: collaborator

Study Sites (3)

Kliniken Essen-Süd, Evang. Krankenhaus Essen-Werden gGmbH

Essen, 45239, Germany

Location

Klinikum Oldenburg, Klinik für Innere Medizin II

Oldenburg, 26133, Germany

Location

University Hospital Ulm

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

vosaroxin; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; 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 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: Prinicipal Investigator

Study Record Dates

• First Submitted: November 2, 2017
• First Posted: November 9, 2017
• Study Start: April 19, 2018
• Primary Completion: October 31, 2019
• Study Completion: October 31, 2019
• Last Updated: October 28, 2020

Record last verified: 2020-10

Locations

DE (3)