Clinical Trials /

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

NCT03338348

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Refractory Anemia with Excess Blasts-2
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Vosaroxin With Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome With Excess Blasts-2
  • Official Title: A Phase II Study With a Safety Run-in Phase Evaluating Vosaroxin With Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia and Intermediate/Adverse Genetic Risk or Myelodysplastic Syndrome With Excess Blasts-2 (MDS-EB-2) - AMLSG 24-15

Clinical Trial IDs

  • ORG STUDY ID: AMLSG 24-15
  • NCT ID: NCT03338348

Conditions

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

Interventions

DrugSynonymsArms
VosaroxinAzacitidine + Vosaroxin
AzacitidineAzacitidine + Vosaroxin

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Azacitidine + VosaroxinOtherCycle 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.
  • Vosaroxin
  • Azacitidine

Eligibility Criteria

        Inclusion Criteria:

          1. 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)

          2. Patients ≥60 years of age

          3. 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

          4. ECOG performance status ≤2

          5. 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)

          6. 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).

          7. Female patients of reproductive age must agree to avoid getting pregnant while on
             therapy and for 3 months after the last dose of vosaroxin.

          8. 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.

          9. 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)

         10. Willing to adhere to protocol specific requirements

         11. 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

        Exclusion Criteria:

          1. Known or suspected hypersensitivity to the study drugs and/or any excipients

          2. 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

          3. Prior treatment for AML except hydroxyurea

          4. Prior treatment for MDS with hypomethylating agents

          5. ECOG performance status >2

          6. Patients who are not eligible for intensive chemotherapy

          7. 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

          8. Active central nervous system involvement

          9. 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

               -  Uncontrolled infection

         10. Severe neurological or psychiatric disorder interfering with ability of giving an
             informed consent

         11. Currently receiving a therapy not permitted during the study, as defined in Section
             10.5.4

         12. Patients with a "currently active" second malignancy other than non-melanoma skin
             cancers. Patients are not considered to have a "currently active" malignancy if they
             have completed therapy and are considered by their physician to be at less than 30%
             risk of relapse within one year.

         13. Known history of positive test for Hepatitis B surface Antigen (HBsAg) or hepatitis C
             antibody or history of positive test for Human Immunodeficiency Virus (HIV)

         14. Hematological disorder independent of leukemia

         15. No consent for registration, storage and processing of the individual disease
             characteristics and course as well as information of the family physician and/or other
             physicians involved in the treatment of the patient about study participation

         16. No consent for biobanking

         17. Current participation in any other interventional clinical study within 30 days before
             the first administration of the investigational product or at any time during the
             study

         18. Patients known or suspected of not being able to comply with this trial protocol

         19. Patients of childbearing potential not willing to use adequate contraception during
             study and 3 months after last dose of therapy

         20. Breast feeding women or women with a positive pregnancy test at Screening visit
      
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of complete remission (CR) and CR with incomplete blood count recovery (CRi)
Time Frame:2 months
Safety Issue:
Description:Efficacy assessments

Secondary Outcome Measures

Measure:CR and CRi in a pre-defined subgroup analysis in patients with complex karyotype
Time Frame:2 months
Safety Issue:
Description:Efficacy assessments
Measure:CR and rate of combined CR/CRi and CR with negativity for minimal residual disease (CRMRD-)
Time Frame:2 months
Safety Issue:
Description:Efficacy assessments
Measure:Duration of response (DOR)
Time Frame:4 years
Safety Issue:
Description:Efficacy assessments
Measure:Event-free survival (EFS)
Time Frame:4 years
Safety Issue:
Description:Efficacy assessments
Measure:Overall survival (OS)
Time Frame:4 years
Safety Issue:
Description:Efficacy assessments
Measure:30-day and 60-day mortality
Time Frame:30 and 60 days
Safety Issue:
Description:Safety assessments
Measure:Incidence and intensity of adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) version v4.0
Time Frame:12 months
Safety Issue:
Description:Safety assessments
Measure:Assessment of Quality of life by the EORTC Quality of Life Core Questionnaire (QLQ-C30)
Time Frame:4 years
Safety Issue:
Description:Quality of life

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Ulm

Trial Keywords

  • Vosaroxin

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