Patients with acute myeloid leukemia (AML) and high risk for induction failure MedDRA version: 17.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Evoltra® 1mg/ml Konzentrat zur Herstellung einer Infusionslösung
Product Name: Clofarabine
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CLOFARABINE
CAS N
Sponsors
Hannover Medical School
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with newly diagnosed acute myeloid leukemia according to WHO classification and aged = 18 years eligible for an intensive induction chemotherapy with high risk for induction failure and for whom currently no molecularly targeted therapy is available: • absence of a t(15;17), t(8;21), inv(16)/t(16;16) and the respective fusion transcripts PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11 • absence of an activating FLT3-mutation (FLT3-ITD or TKD - mutation) • absence of an NPM1 exon12 mutation 2. Written informed consent 3. No previous cytotoxic chemotherapy for the treatment of AML (exception: oral hydroxyurea for up to 5 days during screening/baseline to control hyperleukocytosis) 4. Adequate renal and hepatic functions as indicated by the following laboratory values: • Serum creatinine 60 mL/min/1.73 m2, respectively • Serum bilirubine = 50 years of age at the day of inclusion: Menopause since at least 1 year • Female patients 40 MIU/mL • serum estrogen levels < 30 pg/mL or negative estrogen test • 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral ovariectomy with or without hysterectomy • Correct use of two reliable contraception methods from the time of screening/baseline and during the study for a minimum of 90 days after the last administration of study medication. This includes every combination of a hormonal contraceptive (such as injection, transdermal patch, implant, cervical ring) or of an intrauterine device (IUD) with a barrier method (diaphragm, cervical cap, Lea contraceptive, femidom or condom) or with a spermicide. In case the patient takes hormone preparations for suppression of menstruation during the period of aplasia, a suitable and effective method of contraception has to be discussed with the investigator and used by the patient • General sexual abstinence from the time of screening/baseline, during the study until a minimum of 90 days after the last administration of study medication • Having only female sexual partners • Monogamous relationship with sterile male partner 8. Male patients must meet one of the following criteria: • 6 weeks after surgical sterilization by vasectomy • Correct use of two reliable contraception methods from the time of screening/baseline and during the study for a minimum of 90 days after the last administration of study medication. This includes every combination of a hormonal contraceptive (such as injection, transdermal patch, implant, cervical ring) or of an intrauterine device (IUD) with a barrier method (diaphragm, cervical cap, Lea contraceptive, femidom or condom) or with a spermicide. • General sexual abstinence from the time of screening/baseline during the study until a minimum of 90 days after the last administration of study medication • Having only
Exclusion criteria
Exclusion criteria: 1. Current concomitant chemotherapy, radiation therapy or immunotherapy not defined in the study protocol 2. Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of oral hydroxyurea. The patient must have recovered from all non-hematological acute toxicities from any previous therapy 3. Participation in a clinical trial within 30 days before inclusion in this study or concurrent to this study. 4. Bleeding disorder independent of AML 5. Patients with uncontrolled systemic fungal, bacterial, viral or other infection (defined as persistent disease signs/symptoms without improvement despite appropriate antibiotics or other treatment) 6.Patients with clinically relevant heart disease such as: •History of acute myocardial infarction within the last 6 months •Heart failure NYHA grade III or IV due to myocardial infarction or other causes •Acute inflammatory heart disease •Unstable atrial fibrillation or other hemodynamically relevant arrythmias 7. HIV infection 8. Patients who have received cumulative doses of = 360mg/m2 of doxorubicin or its equivalent to other anrthracyclines, e.g. 900mg/m2 of daunorubicin, 450mg of pegylated liposomal doxorubicin hydrochloride, 225mg/m2 idarubicin or 140mg/m2 mitoxantrone 9. Pregnant or lactating women 10. Any significant concurrent disease, illness, psychiatric disorder or history of serious organ dysfunction that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results 11. Diagnosis of another malignancy, unless the patient is disease-free for at least 3 years following the completion of curative intent therapy, with the following exceptions: • Myelodysplastic syndrome (MDS) in patients with AML after MDS according to the WHO classification • 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. 12. Known hypersensitivity to any of the IMPs
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluation of tolerability and safety of escalating doses of clofarabine in combination with cytarabine and idarubicine in the therapy of previously untreated patients with AML and high risk for induction failure;Primary end point(s): Maximal tolerable dose (MTD) of clofarabine in combination with cytarabine and idarubicine in the therapy of previously untreated AML and high risk for induction failure;Timepoint(s) of evaluation of this end point: MTD will be defined on the basis of the occurrence of dose-limiting toxicities (DLTs) measured within 14 days after start of the first induction cycle (max. 42 days after start of the first induction cycle in case of hematological DLTs);Secondary Objective: •Definition of the recommended dose level of the combination of clofarabine, cytarabine and idarubicine for upcoming phase III trials in the therapy of previously untreated patients with AML and high risk for induction failure •Evaluation of the efficacy of escalating doses of clofarabine in combination with cytarabine and idarubicine in the therapy of previously untreated patients with AML and high risk of induction failure | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Rate of complete remission after two cycles of induction therapy 2. Relapse-free, event-free and overall survival 3. Blast reduction in the bone marrow after the first induction cycle 4. Duration of aplasia 5. Therapy-associated morbidity and mortality 6. Course of molecular and cytogenetic markers during chemotherapy 7. Fraction of patients who receive an alloSCT in CR1;Timepoint(s) of evaluation of this end point: 1. 3 months 2. 2 years 3. max. 42 days after start of the first induction cycle 4. max. 42 days after start of the first induction cycle 5. 2 years 6. 3 months 7. 2 years | — |
Countries
Germany
Contacts
Public ContactClARA clinical trial information
Hannover Medical School, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation
Outcome results
None listed