Clofarabine-cyclophosphamide as Salvage Therapy for Refractory and Relapsed Acute Lymphoblastic Leukemia (ALL) Adults

Inclusion Criteria

• Signed written informed consent according to IGH/EU/GCP and national local laws.
• Age 18-60 years.
• ALL with B-/T-precursor phenotype refractory to first line therapy.
• ALL with B-/T-precursor phenotype 1st isolated bone marrow relapse, occurring 1.5 mg/dl, 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.
• Serum bilirubin ≤ 1.5 x upper limit of normal (ULN).
• Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2.5 x ULN.
• Alkaline phosphatase ≤ 2.5 x ULN.

Exclusion Criteria

• Prior exposure to Clofarabine or, in primary refractory patients only, to Cyclophosphamide during induction courses.
• Patients relapsed > 24 months from first CR. - Philadelphia chromosome-positive (Ph+) ALL.
• Diagnosis of Burkitt-type/B-ALL, or B-/T-lymphoblastic lymphoma with < 25% bone marrow involvement.
• Concurrent or isolated central nervous system (CNS) relapse.
• Pre-existing, uncontrolled pathology such as cardiac disease (congestive/ischemic, acute myocardial infarction within the past 3 months, untreatable arrythmias, NYHA classes III and IV).
• Severe neurological or psychiatric disorder that impairs the patient's ability to understand and sign the informed consent, or to cope with the intended treatment plan.
• Active uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• HIV positive serology or active hepatitis infection. - Concurrent diagnosis of active cancer requiring concurrent chemotherapy and/or radiotherapy, and/or with life expectancy < 1 year.
• Patients who are pregnant or adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of Clofarabine-Cyclophosphamide). Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drugs.