Acute Myelogenous Leukemia MedDRA version: 8.1 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia
Conditions
Interventions
Product Name: CLORETAZINE
Product Code: VNP40101M
Pharmaceutical Form: Injection*
Current Sponsor code: VNP40101M
Other descriptive name: CLORETAZINE
Concentration unit: mg/ml milligram(s)/millilitre
Sponsors
Vion Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria A.Patients must have pathologically confirmed AML, based upon the World Health Organization (WHO) criteria (Appendix A). Patients with acute promyelocytic leukemia (t(15;17)) will be excluded. Patients with favorable cytogenetics (t(15;17), t(8;21), or inv 16) will also be excluded. B.Patients must be = 60 years old and have no prior history of chemotherapy with/without irradiation and no prior history of an antecedent hematologic history (MDS or myeloproliferative disease). In addition, patients must not have received a standard induction regimen containing cytotoxic agents (regimens containing araC or other nucleoside analogues +/- an anthracycline) nor a regimen containing a low-dose single agent cytotoxic chemotherapy (e.g., araC, decitabine, 5-azacytidine). Prior treatment with gemtuzumab ozogamycin is also excluded. C.Patients must have at least one of the following documented poor risk features: •Unfavorable cytogenetics, defined as del (5q)/-5q; -7/del(7q); abnormal 3q, 9q, 11q, 20q, 21q or 17p; t(6; 9); t(9; 22); trisomy 8; complex karyotypes (> 3 unrelated abnormalities), or •ECOG Performance Status = 2 (Appendix B), or •Age > 70 years, or •Cardiac dysfunction which would limit the use of anthracycline therapy, as defined by any one of the following: (i)an ejection fraction =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria A.Patients with secondary AML. Secondary AML is defined as AML that has developed in a patient with a history of an antecedent hematologic disorder, MDS or a myeloproliferative disorder or a history of prior chemotherapy or radiation for a disease other than AML. B.Uncontrolled active infection of any kind. Patients with infections who are under active treatment with antibiotics and whose infections are controlled may be entered to the study. Patients with chronic hepatitis are eligible. C.Patients with favorable cytogenetics including t(15;17), inv16, t(8;21) are excluded. D.Patients with known central nervous system disease E.Patients with ECOG Performance Status 3, or 4. F.Patients concurrently receiving any other standard or investigational treatment for their leukemia, with the exception of hydroxyurea and leukophoresis. G.Patients who have clinical evidence by physical exam, radiologic studies, or tissue biopsies of an ongoing second malignancy unrelated to AML or MDS. H.Because the formulation contains 30% ethanol, patients being treated with disulfiram (Antabuse) are excluded from the study. I.Patients should be off metronidazole (Flagyl) for at least 24 hours prior to starting Cloretazine® (VNP40101M). J.Patients on the screening ECG who demonstrate left bundle branch block, use of an obligate cardiac pacemaker or atrial fibrillation will be excluded from the ECG substudy as will patients with diabetes mellitus treated with insulin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the complete response (CR or CRp) of Cloretazine as a single induction agent in elderly patients, aged 60 years or older, with de novo poor risk AML;Primary end point(s): The primary end point will be when complete response (CR and CRp) to Cloretazine as induction therapy is determined.;Secondary Objective: To determine the probability of overall survival (OS), leukemia-free survival (LFS) and duration of progression-free survival (PFS) as well as the toxicities of Cloretazine® (VNP40101M) in this patient population. To determine the ECG effects with a focus on cardiac repolarization as determined by changes in the QTcF interval duration of Cloretazine® (VNP40101M) in 15-45 patients along with more intense pharmacokinetics at 4 selected sites. | — |
Countries
Germany, United Kingdom
Outcome results
None listed