Clofarabine Salvage Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) (BRIDGE)

Inclusion Criteria:

• Diagnosis of AML according to WHO criteria.

• 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.
• Age above 40 years.

• 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
• Eligibility for intensive chemotherapy
• 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.
• Signed written informed consent.
• Female patients of childbearing potential must have a negative serum
• Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

Exclusion Criteria:

• 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).
• 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.
• Acute promyelocytic leukemia with t(15;17)(q22;q12) molecular detection or (PML/RARα).
• Central nervous system involvement (i.e. WBC ≥ 5/µL in cerebrospinal fluid with blasts present on cytospin).
• Prior allogeneic HCT
• Autologous transplantation within 100 days prior to start of study treatment
• Use of investigational agents or anticancer therapy within 10 days before study entry with the exception of hydroxyurea or low-dose cytarabine.
• 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.
• Patients with known refractoriness to platelet support.
• 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).
• Pregnant or lactating patients.
• 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.