Relapsed or refractory acute lymphoblastic leukaemia (ALL) in children MedDRA version: 8.0 Level: Lowe Classification code 10050281
Conditions
Interventions
Trade Name: CLOLAR
Product Name: Clofarabine
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Clofarabine
Other descriptive name: 2-chloro-9-(2.-deoxy-2.-fluoro-ß-D-arabinofuranosyl)-9H
Sponsors
Bioenvision Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The trial will recruit patients who have failed to achieve response by standard first line therapy or following first relapse, fail to achieve response by standard relapse therapy. Children who have received an allogeneic progenitor cell transplant, must be at least 6-months post transplant. For Inclusion/Exclusion criteria, a ‘prior regimen’ is defined as including one or more of the following: Induction, Consolidation and Maintenance therapies. Patients must meet all of the following criteria for admission in the study. 1. Have a diagnosis of ALL 2. Be =21 years old at time of initial diagnosis. 3. i. Patients with primary, refractory ALL must have an M3 marrow at the end of conventional induction chemotherapy or have an M2 or M3 marrow at the end of no less than 2 prior regimen OR ii Patients with first relapse ALL failing to achieve response following conventional therapy: M3 marrow following re-induction or M2 or M3 following no less than 2 prior regimen OR iii Patients with 2 or more relapses of ALL who have received an allogeneic progenitor cell transplant, must: a. be at least 6-months post transplant b. have good organ function c. be stable with no major complications 4. Must not be eligible for therapy of higher curative potential. Where an alternative therapy has been shown to prolong survival in an analagous population, this should be offered to the patient prior to discussing this study. 5. Have a Karnofsky Performance Status (KPS) of =50 or Lansky Performance Scale of =30 . 6. Provide signed, written informed consent from parent or guardian or young adult patients. 7. Be able to comply with study procedures and follow-up examinations. 8. Have normal cardiac function without treatment. 9. Have adequate organ function as indicated by the following laboratory values, obtained within 7 days prior to registration: Inclusion Laboratory Values: Parameter Required Value Renal Serum creatinine =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from study admission: 1. Received previous treatment with clofarabine. 2. Patients with isolated extramedullary disease. 3. Have received prior bone marrow or peripheral blood stem cell transplant within the last 6 months. 4. Have received prior bone marrow or peripheral blood stem cell transplant more than 6 months ago, but now has compromised organ function. 5. Have an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment. Patients who have had a recent (<30 days) history of fungal or bacterial infection or who are receiving therapeutic doses of antibiotics or anti fungals. 6. Are pregnant or lactating. Male and female patients who are fertile must agree to use an effective means of birth control (i.e., latex condom, diaphragm, cervical cap, etc) to avoid pregnancy. 7. Have psychiatric disorders that would interfere with consent, study participation, or follow-up. 8. Have received any other chemotherapy within the previous 2 weeks and must have recovered from acute toxicity of all previous therapy prior to enrolment. Treatment may start earlier, following consultation with the Medical Monitor, if there is evidence of disease relapse or progression prior to that time. Patients who have received growth factor, cytokine support, leukapheresis, or cranial irradiation will be allowed, but must discontinue treatment 24 hours prior to beginning treatment with clofarabine. 9. Have any other severe concurrent disease, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study. 10. Have recent history of significant renal, hepatic or pulmonary dysfunction, or cardiac dysfunction or on treatment to support cardiac function. 11. Have CNS disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the overall response (OR) rate in paediatric patients with refractory or relapsed ALL. The OR rate is defined as the sum of the number of patients with either complete response (CR) or complete response in the absence of total platelet recovery (CRp) divided by the toal number of patients evaluable for response.;Secondary Objective: 1. To document the rate of CR(s) in the study population. 2. To document the rate of CRp(s) in the study population. 3. To document the rate of partial response (PR(s)) in the study population. 4. To document the modified overall response (MOR) rate in paediatric patients with refractory or relapsed ALL. 5. To document time-to-event parameters including duration of remission and overall survival (OS). 6. To document the safety profile and tolerability of clofarabine for this population and dosing regimen. 7. To document the number of patients receiving bone marrow transplantation or peripheral blood stem cell transplantation and the time to transplant following commencement of Clofarabine. 8. To determine the pharmacokinetic profile and intracellular triphosphate levels of Clofarabine in selected patients. 9. To document the metabolic pathways that may predict Clofarabine sensitivity or resistance.;Primary end point(s): 1. The OR rate will be determined by the sum of the number of patients with either a CR or CRp divided by the total number of patients evaluable for response. 2. The CR rate will be determined by dividing the number of patients with a CR by the total number of patients evaluable for response. 3. The CRp rate will be determined by dividing the number of patients with a CRp by the total number of patients evaluable for response. 4. The PR rate will be determined by dividing the number of patients with a PR by the total number of patients evaluable for response. 5. The MOR rate will be determined by the sum of the number of patients with either a CR, a CRp or a PR divided by the total number of | — |
Countries
Austria, Italy
Outcome results
None listed