An Open-Label, Single-Arm, Multi-Center, Phase II/III study of Troxatyl (Troxacitabine) Administered by Continuous Infusion in Patients with Acute Myeloid Leukemia (AML) in second salvage
- Conditions
- Acute Myeloid Leukemia (AML)
- Registration Number
- EUCTR2005-001721-29-DE
- Lead Sponsor
- SGX Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 211
- Patients must have a confirmed diagnosis of Acute Myeloid Leukemia according to the World Health Organization (WHO) classification (except for acute promyelocytic leukemia (APL)).
- Patient must have received at least two previous coursed of induction chemotherapy to be considered in the second salvage setting i.e. 1) have never achieved CR or CRp with two prior different cytotoxic induction regimens, or 2) have relapsed after a first CR or CRp and failed to respond to a cytotoxic first salvage therapy, or 3) have relapsed after < 6 months from a second CR or CRp
- Patient bone marrow aspirates and/or biopsies must contain >= 10% blasts.
- Previous bone marrow transplantation patients will be allowed.
-Leukemia relapse or persistence must be confirmed by recurrence of blasts in peripheral blood, bone marrow histopathology and/or histological proven extramedullary disease.
- There is no restriction on number of regimens or type of treatment administered for consolidation in first or second CR (or CRp).
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of <= 2 and an estimated life expectancy of at least eight weeks.
- Patients must be >= 18 years old.
- Male, or female patients who are post-menopausal (amenorrhagic for at least 12 months), or surgically or biologically sterile. Females of childbearing potential with a negative serum pregnancy test prior to entering the study and using adequate forms of contraception for the duration of the study, including 30 days after the last treatment. Males should avoid fathering children during the course of the study, and adequate methods of contraception should be used by both male and female patients. Patients and their partners with reproductive potential must use an effective contraceptive method while the patient is on the study treatment and for 30 days after the last treatment. Adequate methods of contraception are double barrier methods (condoms with spermicidal jelly or foam, birth control patch /e.g., Ortho Evra), NuvaRing, and diaphragm with spermicidal jelly or foam), oral, depot and injectable contraceptives, IUD, and surgical sterilization. Single barrier methods, rhythm methods, will not be
considered adequate contraception .
- Patients must have following laboratory values:
Parameter LaboratoryValues
Estimated Serum creatinine clearance>=45 mL/min
Total Bilirubin <= 2.0mg/dL (<= 34.2µmol/L)
AST (SGOT) or ALT (SGPT) <= or equal 3 X ULN*
*ULN: Institution’s upper limit of normal.
- The patient must understand and be able and willing and likely to fully comply with study procedures, including scheduled follow-up.
- The patient must have given written personally signed and dated informed consent to participate in the study, in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines, before completing any study related procedures.
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
- Ongoing clinical significant toxicities from previous treatments for AML.
- Patients who have experienced a Grade 3/4 skin rash or any grade hand -foot syndrome with prior anti-leukemia therapy.
- Clinical evidence of active CNS leukemic involvement.
- Active and uncontrolled infection. Patients with infections that are under active treatment with antibiotics and whose infections are controlled may be entered to the study. Patients with chronic hepatitis are eligible.
- Clinical evidence by tumor marker, pathology, or radiological studies of an active second malignancy.
- Uncontrolled medical problems, unrelated to the malignancy, or of sufficient severity that in the opinion of the investigator, impair a patient’s ability to give informed consent or unacceptably reduce the safety of the proposed treatment.
- Neurological or psychiatric disorders that would interfere with consent or study follow-up.
- Known or suspected intolerance or hypersensitivity to the study materials [or closely related compounds], lamivudine, or any of the stated ingredients including mannitol within the study materials.
- Patients with a history of alcohol or other substance abuse within the last year will be excluded.
- Patients cannot have received any treatment other than hydroxyurea as second salvage. Hydroxyurea should be discontinued at least 24 hours prior to initiation of protocol treatment.
- Female patients who are pregnant or lactating or females with a positive pregnancy test at screening must be excluded.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to determine the complete response (CR) rate of a 5-day continuous IV infusion of troxacitabine 12 mg/m2 day given as second salvage therapy in adult patients with AML.;Secondary Objective: - To determine overall, relapse-free and event-free survival and remission duration.<br>- To determine the duration of response.<br>- To determine the complete response with incomplete platelet recovery (CRp) rate.<br>- To determine the tolerability and safety of 5-day continuous IV infusion of troxacitabine.<br>- To determine the relationship between troxacitabine plasma concentrations, <br>antileukemic activity and adverse events.<br>;Primary end point(s): CR
- Secondary Outcome Measures
Name Time Method