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

• Status: Completed
• Trial end date: 2017-03-11
• Target enrollment: 0
• Participant gender: 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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Treatments: Clofarabine; Cyclophosphamide

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.