Treatment Refractory or Relapsed Acute Myeloid Leukemia MedDRA version: 9.1 Level: LLT Classification code 10066353 Term: Treatment related acute myeloid leukemia
Conditions
Interventions
Product Name: Tosedostat
Product Code: CHR-2797
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: tosedostat
Current Sponsor code: CHR-2797
Concentration unit: mg milligram(s)
Concentration type
Sponsors
Chroma Therapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed, informed consent prior to any study specific procedure. 2. Subjects with a confirmed diagnosis of AML according to WHO classification (excluding acute promyelocytic leukemia [APL]) who have had either a first CR lasting less than 12 months, or have not had a first CR and who will receive their first salvage therapy in this study [6]. For the purposes of this study, the following considerations apply: • Subjects may have received one induction course comprised of one or two cycles provided both were with the same agents even if different doses were used. • Induction cycles should normally use agents and doses considered as standard of care for induction at the investigational site concerned. An induction cycle would normally require at least part of the induction regimen to consist of approved agents. An induction regimen comprised only of low dose chemotherapy would not normally be considered suitable. • Subjects may have received consolidation for any number of cycles. Consolidation will be considered as any regimens given while the subject was in remission after 1-2 induction cycles. • Subjects who received hematopoietic stem cell transplant (HSCT) in first remission are eligible provided there has been no chemotherapy or other targeted therapies to treat a relapse. Donor leukocyte infusion (DLI) is allowed provided there is no evidence of hematologic relapse as defined by the International Working Group (IWG). 3. Subjects should have recovered from the adverse effects of prior therapies to grade =1 (according to CTCAE v3) (excluding alopecia and any adverse effects that are expected to be chronic & stable). 4. Subjects should have not received prior therapy for first relapse or for refractory disease (a second induction cycle is allowed as defined above). 5. Subjects must have bone marrow aspiration performed within four weeks prior to study entry showing the subject is neither a CR nor CRp. This may be done at the Screening visit if appropriate and feasible. 6. Subjects must have adequate hepatic and renal function including the following: • Total bilirubin = 1.5 x upper limit of normal. • AST and ALT = 2.5 x upper limit of normal. • Serum creatinine = 1.5 x upper limit of normal. 7. Age = 65 years. 8. Performance status (PS) = 2 (ECOG scale). 9. Screening left ventricular ejection fraction (LVEF) = 50% 10. Subject is able to comply with all study procedures during the study including all visits and tests. 11. Male subjects with female partners of reproductive potential must use acceptable contraceptive methods for the duration of time on study and continue to do so for a further 3 months after the end of tosedostat treatment. 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
Exclusion criteria: 1. Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of any other investigational agents within 2 weeks prior to trial entry (with the exception of hydroxyurea which can be used in certain circumstances). 2. Subjects with APL (FAB type M3) or CML in blast crisis. 3. Any co-existing medical condition that in the investigator’s judgment will substantially increase the risk associated with the subject’s participation in the study. 4. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures. 5. Significant* cardiovascular disease defined as: • Congestive heart failure NYHA class 4 • Unstable angina pectoris • History of myocardial infarction within 6 months prior to study entry • Presence of clinically significant valvular heart disease • Uncontrolled or clinically significant ventricular arrhythmia • Presence of clinically significant conduction defect on screening ECG • Uncontrolled hypertension (i.e., systolic BP >160mmHg, diastolic >90 mmHg in repeated measurements) despite adequate therapy • Clinically significant atrial fibrillation. *Grade 3/4 in the NCI CTCv3.0 grading would generally be considered clinically significant, although this remains a judgment for the Investigator to make. 6. Gastrointestinal disorders that may interfere with absorption of drug. 7. Clinically significant interstitial lung disease. 8. Subjects with grade III–IV peripheral neuropathy [or central nervous system leukemia].
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the efficacy of tosedostat in elderly subjects with treatment refractory or relapsed AML by measuring CR and CRp. ;Secondary Objective: Secondary objectives of the study are: • To evaluate the safety and tolerability of tosedostat in elderly subjects with treatment refractory or relapsed AML • To evaluate the efficacy of tosedostat in elderly subjects with treatment refractory or relapsed AML, as determined by measures other than CR and CRp for the type and duration of response. Exploratory objectives of the study include: • Determination of the pharmacokinetics of tosedostat in elderly subjects with treatment refractory or relapsed AML. • Evaluation of the efficacy of tosedostat using additional exploratory definitions of response.;Primary end point(s): The primary efficacy endpoint is defined as the proportion of subjects that achieve CR or CRp at any time during the study, as determined by central laboratory review. The number and proportion of subjects achieving CR or CRp at any time during the study will be presented. The 95% confidence interval around the observed proportion of subjects achieving CR or CRp at any time during the study will also be calculated, based on the number of events in the appropriate binomial distribution. | — |
Countries
Netherlands
Outcome results
None listed