- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03338348
Study of Vosaroxin With Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome With Excess Blasts-2
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
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
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Essen, Germany, 45239
- Kliniken Essen-Süd, Evang. Krankenhaus Essen-Werden gGmbH
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Oldenburg, Germany, 26133
- Klinikum Oldenburg, Klinik für Innere Medizin II
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Ulm, Germany, 89081
- University Hospital Ulm
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- Uncontrolled infection
- Severe neurological or psychiatric disorder interfering with ability of giving an informed consent
- Currently receiving a therapy not permitted during the study, as defined in Section 10.5.4
- 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.
- 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)
- Hematological disorder independent of leukemia
- 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
- No consent for biobanking
- 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
- Patients known or suspected of not being able to comply with this trial protocol
- Patients of childbearing potential not willing to use adequate contraception during study and 3 months after last dose of therapy
- Breast feeding women or women with a positive pregnancy test at Screening visit
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
OTHER: Azacitidine + Vosaroxin
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. |
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 .
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of complete remission (CR) and CR with incomplete blood count recovery (CRi)
Time Frame: 2 months
|
Efficacy assessments
|
2 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
CR and CRi in a pre-defined subgroup analysis in patients with complex karyotype
Time Frame: 2 months
|
Efficacy assessments
|
2 months
|
CR and rate of combined CR/CRi and CR with negativity for minimal residual disease (CRMRD-)
Time Frame: 2 months
|
Efficacy assessments
|
2 months
|
Duration of response (DOR)
Time Frame: 4 years
|
Efficacy assessments
|
4 years
|
Event-free survival (EFS)
Time Frame: 4 years
|
Efficacy assessments
|
4 years
|
Overall survival (OS)
Time Frame: 4 years
|
Efficacy assessments
|
4 years
|
30-day and 60-day mortality
Time Frame: 30 and 60 days
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Safety assessments
|
30 and 60 days
|
Incidence and intensity of adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) version v4.0
Time Frame: 12 months
|
Safety assessments
|
12 months
|
Assessment of Quality of life by the EORTC Quality of Life Core Questionnaire (QLQ-C30)
Time Frame: 4 years
|
Quality of life
|
4 years
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Anemia
- Precancerous Conditions
- Anemia, Refractory
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Preleukemia
- Anemia, Refractory, with Excess of Blasts
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Azacitidine
Other Study ID Numbers
- AMLSG 24-15
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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