acute myeloid leukeamia MedDRA version: 19.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Vidaza
Product Name: Vidaza
Pharmaceutical Form: Lyophilisate for suspension for injection
INN or Proposed INN: AZACITIDINE
CAS Number: 320-67-2
Current Sponsor code: Azacitidine
Concentra
Sponsors
Universität Leipzig
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet ALL of the following criteria to be enrolled in the study: 1. Newly diagnosed (within the last 28 days) and untreated AML (> 20% blasts in the bone marrow based on the WHO classification) including: - de novo AML - AML secondary to prior myelodysplastic disease - AML secondary to exposure to potentially leukemogenic therapies or agents (eg, radiation therapy, alkylating agents, topoisomerase II inhibitors) with the primary malignancy in remission for at least 2 years 2. Age > 60 years 3. Eligible for intensive chemotherapy and allogeneic hematopoietic cell transplantation 4. Serum bilirubin levels = 1.5 x the upper limit of normal (ULN). Higher levels are acceptable if these can be attributed to - active hemolysis (as indicated by positive direct Coombs’ testing, decreased haptoglobin level, elevated indirect bilirubin and/or lactate dehydrogenase [LDH]), - or ineffective erythropoiesis (as indicated by bone marrow findings) 5. Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) level = 2 x ULN 6. Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) level = 2 x ULN 7. serum creatinine levels = 1.5 x ULN 8. Left ventricular ejection fraction by echocardiography > 50% 9. Women of childbearing potential may participate, providing they meet the following conditions: • must agree to use effective contraceptive methods throughout the study and for 6 months following the date of the last dose of study medication • must have a negative serum pregnancy test obtained within 72 hours prior to day 1. 10. Males with female partner of childbearing potential must agree to use effective contraceptive methods throughout the study and should avoid fathering a child for 6 months following the date of the last dose of study medication. 11. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Appendix A) 12. Capable of giving informed consent 13. Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 38 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 75
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria will not be included in the study 1. Acute promyelocytic leukaemia (AML M3) 2. Previous cytotoxic or any other hypomethylating or biological treatment for AML, exception: hydroxyurea 3. Any diagnosis of malignant disease within the previous 12 months (excluding basal cell carcinoma with no complications) 4. Hepatic tumors in the medical history 5. Known or suspected hypersensitivity to azacitidine (incl. additives), Mitoxantrone (incl. additives), Ara-C (incl. additives) 6. Patients with serious concomitant medical illness: - severe congestive heart failure [grade = 3 according to CTCAE] or - clinically unstable ischemia or - acute myocardial infarction in the previous six months or - pulmonary hypertension [grade > 3 according to CTCAE] or - severe cardiac arrythmias [grade > 3 according to CTCAE] or - chronic pulmonary diseases [grade > 3 according to CTCAE] or - uncontrolled hypertension or - uncontrolled diabetes or - uncontrolled severe infections [grade > 3 according to CTCAE] or - any other severe or uncontrolled medical illness 7. Psychiatric illness that would prevent granting of informed consent 8. Active viral infection with known human immunodeficiency virus (HIV) or viral hepatitis type B or C 9. Treatment with any of the following concomitant medications: - Corticosteroids, unless otherwise indicated, e.g. blood product transfusion reaction or prevention - Retinoids - Cytokines (except as outlined in Section 3.2.1) - Interleukin-11 - EPO 10. Participation in other clinical trials in the last 30 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of the trial is to assess efficacy and safety of induction therapy with response-adapted sequential azacitidine and conventional AML induction chemotherapy in patients > 60 years with newly diagnosed AML (at the dose level resulting from the dose evaluation phase of the trial). Primary objective To assess efficacy in terms of the overall response rate (ORR) till day 90 including: - Complete remissions (CR) - Complete Remission with incomplete blood count recovery (CRi) - Partial remissions (PR);Secondary Objective: - Safety of response-adapted sequential azacitidine and chemotherapy - Overall survival one year after start of trial therapy - Overall survival two years after start of trial therapy - Event-free survival one and two years after start of trial therapy - Days alive and out of hospital - Rate of treatment failure according to IWG response criteria - Number of patients undergoing HCT - Correlate study endpoints with the points achieved at the time of diagnosis according to the following questionnaire: instrumental activities of daily living (iADLs, “Instrumentelle Aktivitäten des täglichen Lebens”) - Correlate study endpoints with the Eastern Cooperative Oncology Group (ECOG) Performance Status at the time of diagnosis - Compare response and survival in patients treated with response-adapted sequential azacitidine and chemotherapy with historical patient populations treated with the same conventional chemotherapy;Primary end point(s): The primary endpoint of the phase II part of the trial is the overall response rate on day 90. Overall response rate (ORR) includes: - Complete remissions (CR) - Complete Remission with Incomplete Blood Count recovery (CRi) - Partial remissions (PR) ;Timepoint(s) of evaluation of this end point: - Screening/Baseline - During Azacitidine application and induction chemotherapies - Adaption/Response assessment (days 15, 69, 90) - once weekly during the first azacitidine cycle, on days 1 and 15 o | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety of response-adapted sequential azacitidine and chemotherapy. Safety will be assessed in terms of adverse events and laboratory values. Overall survival one and two years after start of trial therapy Survival data will be collected throughout the study for each subject. The secondary efficacy variable, time to death from any cause, is defined as the time between enrolment and death from any cause. All subjects will be followed until drop-out, death, or study termination. This includes patients with premature study termination. Event-free survival is defined as time from enrolment to one of the following events: - disease progression (according to IWG criteria), - relapse after CR or CRi, - death of any cause. Subjects who drop out or are alive at study termination will have their overall survival times censored at the time of last contact, as appropriate. Rate of treatment failure on day 90 according to IWG response criteria. Treatment failure includes cases of aplasia and intermediate causes according to the definition of treatment failure by the IWG response criteria for AML. Description of efficacy in terms of overall response, survival and event-free survival by subgroups: - patients with azacitidine alone - patients with azacitidine and conventional induction chemotherapy Days alive and out of hospital This endpoint will encompass the whole individual study period of two years. Information on each hospitalization will be collected. This includes information on start and end of hospital stay, reason for hospitalization (e.g., disease progression, AML-related illness, treatment-related adverse event), as well as information on the actual treatment setting (azacitidine resp. conventional induction chemotherapy). Every day a patient is alive and completely outside a hospital is counted. In case a patient is lost to follow-up before end of the two years study period, days after drop-out will not be counted. Number of patie | — |
Countries
Germany
Contacts
Public ContactStudiensekretariat Hämatologie
Universität Leipzig
Outcome results
None listed