Clofarabine-cyclophosphamide as Salvage Therapy for Refractory and Relapsed Acute Lymphoblastic Leukemia (ALL) Adults
Condition: Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: Clofarabine, Cyclophosphamide
Intervention description: The proposed treatment schedule consists of a combination of Clofarabine plus Cyclophosphamide administered over 5 consecutive days (Treatment scheme).
Intervention MeSH terms: Cyclophosphamide; Clofarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Adult patients; Refractory; Relapsed; clofarabine; cyclophosphamide; refractory and relapsed acute lymphoblastic leukemia; ALL

Summary:

      This is a multicentric, prospective pilot trial testing a Clofarabine-Cyclophosphamide
      combination to treat refractory and first bone marrow relapse adult ALL, for the achievement
      of a complete remission (CR) and the concurrent evaluation of biological response in ALL
      cells (minimal residual disease, apoptosis and DNA cell damage, pharmacogenomics).
    

Eligibility criteria:

        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 < 24
             months from the achievement of first CR, after chemotherapy or hematopoietic stem-cell
             transplantation (HSCT) defined as follows:

             * ≥ 5% leukemic blasts in the bone marrow not attributable to another cause (e.g.
             marrow regeneration); if there are no circulating blasts and the bone marrow contain
             5-20% leukemic blasts, a repeat bone marrow performed at least a week later is
             necessary to confirm relapse.

          -  ECOG performance status 0-2 or reversible ECOG 3 score following intensive care of
             complications.

          -  Adequate hepatic and renal function, unless considered due to organ leukemic
             involvement:

               -  Serum creatinine <1.5 mg/dl; if serum creatinine >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.