A phase II study of Cloretazine for elderly patients with de novo poor risk acute myelogenous leukemia.
- Conditions
- Acute Myelogenous Leukemia
- Registration Number
- EUCTR2006-001853-89-GB
- Lead Sponsor
- Vion Pharmaceuticals, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 85
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 < 50%, or (ii)a history of significant coronary artery disease (one or more vessel stenosis requiring medical treatment, stent placement or surgical bypass graft), or (iii)a history of congestive heart failure or myocardial infarction, or (iv)a significant arrhythmia including atrial fibrillation or flutter, sick sinus syndrome, or ventricular arrhythmia, or (v)heart valve disease (excluding mitral valve prolapse), or (vi)other heart disease (must be approved by the sponsor). Patients with a history of heart disease as defined above must be on appropriate medication(s) and have their disease under control. •Pulmonary dysfunction assumed not to be related to the patient’s AML, as defined by DLCO and/or FEV1 < 80% or dyspnea on slight activity or at rest, or requiring oxygen, or •Hepatic dysfunction related to (i) chronic hepatitis, or (ii) liver cirrhosis •Other organ dysfunction or comorbidity that precludes standard cytotoxic induction treatment, such as 3+7”, with sponsor approval
D.Patients must have the following clinical laboratory values within 24 hours prior to beginning protocol treatment: 1.Serum creatinine ? 2.0 mg/dl. 2.Total bilirubin ? 2.0 mg/dl. 3.Alanine aminotransferase (ALT/SGPT), or aspartate aminotransferase (AST/SGOT) ? 5x the upper limit of normal
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the complete response rate (CR or CRp) of Cloretazine® (VNP40101M) 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.<br><br> 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.
- Secondary Outcome Measures
Name Time Method