A study with a combination of two anticancer drugs as a salvage therapy for patients, affected by acute leukaemia aiming at lymphocites, adult not respondent to previous therapies or with a relapsing leukaemia.

Phase 1

• Conditions: Acute Lymphoblastic Leukemia (ALL); MedDRA version: 14.1Level: LLTClassification code 10000844Term: Acute lymphoblastic leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2010-019742-12-IT
• Lead Sponsor: G.I.M.E.M.A. GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL'ADULTO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-06-08
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

-Age 18-60 years.
-ALL with B-/T precursor phenotype refractory to first line therapy.
-ALL with B-/T precursor phenotype with 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 contains 5-20% leukemic blasts, a repeat bone marrow performed at least one week later is necessary to confirm relapse.
-An 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.
-Women of childbearing potential must have a negative serum pregnancy
-Signed written informed consent according to ICH/EU/GCP and national local laws.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 27
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-Prior exposure to Clofarabine or, in primary refractory patients, to Cyclophosphamide during the induction courses.
-Patients relapsed >24 months from first CR.
-2nd or subsequent bone marrow relapse
- 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 arrhythmias, 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 a life expectancy <1 year.
-Patients who are pregnant (women of childbearing potential must have a negative serum pregnancy test). Post-menopausal women must be amenorrhoic for at least 24 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this trial is to assess the activity - in terms of percentage of CR - of Clofarabine in combination with Cyclophosphamide in adult patients with refractory and relapsed (=24 months from first CR) ALL.;Secondary Objective: -To assess the safety and tolerability of Clofarabine when used in combination with Cyclophosphamide. The chosen indicator of feasibility is incidence rate of severe toxic side effects as evaluated by means of the Common Toxicity Criteria (CTC) scale<br>-To assess minimal residual disease (MRD) status after treatment.<br>-To assess disease-free survival (DFS) at 1 year.<br>-Overall survival (OS) at 1 year.<br>-Cumulative incidence of relapse (CIR) at 1 year.<br>-DFS, OS and CIR in different risk groups.;Primary end point(s): The rate of patients in CR after induction therapy.;Timepoint(s) of evaluation of this end point: At the end of the induction therapy.