Acute myeloid leukaemia MedDRA version: 12.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia MedDRA version: 12.1 Level: LLT Classification code 10000880 Term: Acute myeloid leukaemia
Conditions
Interventions
Trade Name: Evoltra
Product Name: Clofarabine
Product Code: Clofarabine
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CLOFARABINE
CAS Number: 123318-82-1
Concentratio
Sponsors
University of Leipzig
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of AML as defined by WHO 2. Primary or secondary AML 3. Age =60 years 4. Not eligible for standard/”curative” chemotherapy as described at the end of this section in refer-ence tables in section 4.3. 5. Adequate renal and hepatic functions as indicated by ALL of the following laboratory values: a. Serum creatinine less than or equal 1.0 mg/dL (less than or equal 88,4 µmol/l) or if serum creatinine >1.0 mg/dL (>88,4 µmol/l), then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black) b. Serum bilirubin =1.5 mg/dL (17,1 µmol/l) × upper limit of normal (ULN) c. Aspartate transaminase (AST)/ alanine transaminase (ALT) less than or equal 2.5 × ULN d. Alkaline phosphatase less than or equal 2.5 × ULN 6. Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. 7. Written informed consent (ICF) 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: Patients meeting ANY of the following criteria will not be included in the study: 1. Diagnosis of AML M3 2. Current concomitant chemotherapy, radiation therapy, or immunotherapy other than described in section 5.2 and 5.3 of the trial protcol. 3. Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy. 4. Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment. 5. Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). 6. Hypersensitivity to Clofarabine, AraC or one of their components. 7. Pregnant or nursing women. 8. Any significant concurrent disease, illness, or psychiatric disorder that would compromise pa-tient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results. 9. Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy, with the following exceptions: • Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. • Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed. 10. Psychiatric illness that would prevent granting of informed consent. 11. Active viral infection with known human immunodeficiency virus (HIV) or viral hepatitis type B or C. 12. Ongoing drug abuse. 13. Women with child bearing potency without effective contraception (i. e. implants, injectables, combined oral contraceptives, some IUDs or vasectomised partner) during the conduct of the trial. Patients using hormonal methods of contraception must be informed about possible influ-ences of the study drug on contraception. 14. Concomitant participation in other clinical trials.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I – Dose evaluation To investigate feasibility of induction therapy with low dose Ara-C (20 mg/m2 sc injection d1-d14) and clofarabine at three different dose levels for the first induction cycle (Clofarabine 10, 15 or 20 mg/m2 1h iv infusion d1-d5). Phase II – Safety To assess safety (in terms of AEs/ARs, SAEs/SARs and Adverse reactions CTC grade 4 (AR4)) of induction therapy with low dose AraC in combination with Clofarabine (at the dose level resulting from the dose evaluation phase of the trial). ;Secondary Objective: To determine the efficacy in terms of - Response after induction therapy [incidence of complete re-mission (CR), complete remission with incomplete recovery (CRi), partial response (PR), resistant disease (RD), death during induction therapy] - overall survival (OS) - event-free survival (EFS) - relapse-free survival (RFS) of low dose AraC in combination with Clofarabine (at the dose level resulting from the dose evaluation phase of the trial) To compare CR rates and overall survival with those of patients treated in the curative and palliative arm of the OSHO study for patients >60 years (OSHO #69). To analyze the subgroup of patients with intermediate and high risk cytogenetics To determine the feasibility of allogeneic hematopoietic cell transplantation after reaching CR at the end of induction therapy.;Primary end point(s): • Adverse and serious adverse events during induction therapy • Adverse and serious adverse reactions during induction therapy • Adverse reactions CTC grade 4 (AR4), defined as any case of adverse reactions CTC grade 4 occurring within 14 days of the individually first induction cycle - excluding deaths due to infections and leukaemia-related deaths. | — |
Countries
Germany
Outcome results
None listed