Patients with high risk acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS) scheduled for allogeneic stem cell transplantation (SCT). MedDRA version: 18.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.0 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and u
Conditions
Interventions
Trade Name: Evoltra® 1mg/ml Konzentrat zur Herstellung
einer Infusionslösung
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CLOFARABINE
CAS Number: 123318-82-1
Concent
Sponsors
Hannover Medical School
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent 2. Age = 18 at the day of inclusion 3. Patients with high risk AML or advanced MDS (IPSS score = intermediate 2) scheduled for an allogeneic SCT from HLA-matched related or unrelated donor 4. Amount of blasts 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be > 60 mL/min/1.73 m2 • Serum bilirubin = 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 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 oral, 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, 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 10. 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 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 oral, 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, during the study until a minimum of 90 days after the last administration of study medication • Having only male sexual partners • Monogamous relationship with sterile female partner 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
Exclusion criteria
Exclusion criteria: 1. Patients with acute promyelocytic leukemia with t(15;17) 2. Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol 3. Any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy 4. Current participation in any other clinical trial and/or participation in another clinical trial within 30 days before the trial begins (Exception: Parallel follow-up of any other trial at least 30 days after end of intervention) 5. Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart (heart insufficiency = NYHA II), kidney (serum creatinine > 1.5 x normal serum level), liver (bilirubin > 1.5 x normal serum level, AST / ALT, AP > 5 x normal serum level), or other organ system that may place the patient at undue risk to undergo treatment 6. 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) 7. Human immunodeficiency virus (HIV) positivity 8. Pregnant or lactating patients 9. Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results 10. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: 1. Overall and relapse-free survival 2. Morbidity and mortality after allogeneic SCT with focus on cardiac toxicity 3. Rate of engraftment 4. Kinetics of chimerism after allogeneic SCT Assessment of safety: To evaluate the toxicity and safety of clofarabine in combination with ara-C and in comparison to FLAMSA in the setting of allogeneic SCT in patients with high risk AML or advanced MDS. ;Main Objective: To demonstrate that event-free survival is improved by using ClAraC instead of the FLAMSA regimen.;Primary end point(s): Event-free survival;Timepoint(s) of evaluation of this end point: 18 months after stem cell Tx (last patient in) - approx. 72 months after stem cell Tx (first patient in). In case of death: timepoint of death. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall and relapse-free survival 2. Morbidity and mortality after allogeneic stem cell transplantation with focus on cardiac toxicity 3. Rate of engraftment 4. Kinetics of chimerism after allogeneic stem cell transplantation Safety endpoints: Toxicity and safety of clofarabine in combination with ara-C (ClAraC) and in comparison to FLAMSA;Timepoint(s) of evaluation of this end point: Secondary end points 1.-4.: 18 months after stem cell Tx (last patient in) - approx. 72 months after stem cell Tx (first patient in). In case of death: timepoint of death. Safety endpoints: 30 days after stem cell Tx | — |
Countries
Germany
Contacts
Public ContactClAraC clinical trial information
Hannover Medical School, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation
Outcome results
None listed