Patients with AML >40 years of age with untreated relapse or refractory disease after a minimum of one standard induction therapy. MedDRA version: 14.1 Level: LLT Classification code 10060557 Term: Acute myelocytic leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Evoltra
Product Name: Evoltra
Pharmaceutical Form: Concentrate for solution for infusion
Sponsors
Dresden Universtity of Technology
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1) Diagnosis of AML according to WHO criteria. (2) Untreated relapse or refractory disease after a minimum of one standard induction therapy. Treatment of relapse with leukocyte-apheresis or up to 5 days with low dose cytarabine or hydroxyurea is allowed. • Refractory disease is defined as =5% blasts after the second cycle of induction therapy or no reduction in marrow blasts at early treatment assessment (day +15) after the first cycle of induction therapy. • Relapse is defined as an increase in bone marrow blast count =5%, re-appearance of blasts in the peripheral blood or extramedullary disease. (3) Age above 40 years. (4) Have adequate renal and hepatic functions as indicated by the following laboratory values: • Serum creatinine =1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m2 (see reference below*) • Serum bilirubin =1.5× upper limit of normal (ULN) • Aspartate transaminase (AST)/alanine transaminase (ALT) =2.5× ULN • Alkaline phosphatase =2.5× ULN (5) Eligibility for intensive chemotherapy (6) Patient needs to be capable to understand the clinical trial as an investigational approach to bridge the time to potential allogeneic HCT, potential risks and benefits of the study. (7) Signed written informed consent. (8) Female patients of childbearing potential must have a negative serum pregnancy test within 3 days prior to enrollment. (9) Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment. * Calculation of Creatinine Clearance by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black). 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 84 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 84
Exclusion criteria
Exclusion criteria: (1) For refractory disease, more than two prior induction chemotherapies or more than one prior salvage chemotherapy containing high-dose cytarabine (cumulative dose of cytarabine = 5 g/m2). (2) Second or higher relapse. Patients who received hypomethylating agents like azacytidine or decitabine as a treatment of first relapse, respond and relapse later on may be included. (3) Acute promyelocytic leukemia with t(15;17)(q22;q12) molecular detection or (PML/RARa). (4) Central nervous system involvement (i.e. WBC = 5/µL in cerebrospinal fluid with blasts present on cytospin). (5) Prior allogeneic HCT (6) Autologous transplantation within 100 days prior to start of study treatment (7) Use of investigational agents or anticancer therapy within 10 days before study entry with the exception of hydroxyurea or low-dose cytarabine. (8) 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 transplantation. (9) Patients with known refractoriness to platelet support. (10) 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). (11) Pregnant or lactating patients. (12) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To study the safety and efficacy of clofarabine salvage therapy prior to allogeneic HCT. (Rate of treatment success);Secondary Objective: - rate of treatment success by risk group - rate of HCT - rate of adverse drug reactions - cause-specific treatment failure;Primary end point(s): Rate of treatment success (Treatment success is defined as complete remission after salvage therapy with clofarabine only or after bridging therapy with clofarabine together with conditioning prior to allogeneic HCT.);Timepoint(s) of evaluation of this end point: after completion of study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Rate of treatment success by risk group, rate of HCT, rate of adverse drug reactions, cause-specific treatment failure | — |
Countries
Germany
Contacts
Public ContactHead of Clinical Trials Unit
Universitätsklinikum Dresden, Med. Klinik und Poliklinik I
Outcome results
None listed