EFFICACY AND TOLERABILITY EVALUATION OF CLOFARABINE, CYTARABINE AND LIPOSOMAL DOXORUBICIN IN CHILDREN WITH EITHER LYMPHOBLASTIC OR MYELOID RELAPSED OR REFRACTORY ACUTE LEUKEMIA AND IN CHILDREN WITH SECONDARY ACUTE MYELOID LEUKEMIA
- Conditions
- RELAPSED/REFRACTORY PEDIATRIC ACUTE EITHER LYMPHOBLASTIC OR MYELOID LEUKEMIA AND SECONDARY ACUTE MYELOID LEUKEMIA.MedDRA version: 14.1Level: LLTClassification code 10060356Term: Acute myeloid leukaemia without mention of remissionSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: PTClassification code 10059034Term: Acute myeloid leukaemia recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: LLTClassification code 10060352Term: Acute lymphoid leukaemia without mention of remissionSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: LLTClassification code 10063621Term: Acute lymphoblastic leukaemia recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-004893-28-IT
- Lead Sponsor
- AZIENDA SANITARIA OSPEDALIERA O.I.R.M. - S. ANNA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
- Age at diagnosis between 1 and 21 years (20 years and 364 days) - Second or subsequent isolated bone marrow relapses of ALL - Refractory ALL - First or subsequent isolated bone marrow relapses of AML - Either refractory or secondary AML in patients who received previous chemotherapy - Lansky or Karnofsky Performance Status score > 60% - Life expectancy > 6 weeks - Normal Heart function (VEF = 55% 2-D echocardiography) and history negative for concomitant medication to treat cardiopathy -Good organ function defined by: 1) serum creatinine <2 times the upper limit for age, 2) total bilirubin <1.5 times the upper limit of age, 3) transaminases = 2.5 times the upper limit for age, 4) alkaline phosphatase = 2.5 times the upper limit for age -For female patients with childbearing potential, a negative test for pregnancy is to be considered before entry on study -Male and female patients must use an effective contraceptive method during the study and for a minimum of 3 months after study treatment; -Written signed informed consent from patients or from parents or legal guardians for minor patients, according to local law and regulations
Are the trial subjects under 18? yes
Number of subjects for this age range: 40
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
-Isolated extramedullary relapse of ALL and AML -First isolated bone marrow relapse of ALL -Patients with involvement of central nervous system (CNS) at diagnosis of refractory / relapse of ALL and AML or of secondary AML -Early (<3 months) bone marrow relapse after HSCT (hematopoietic Stem Cell Transplantation) -acute promyelocytic leukemia -Acute leukemia in first or subsequent isolated bone marrow relapse or refractory in patients with Down Syndrome - Current or recent (<30 days) history of either fungal or bacterial infections requiring treatment at diagnosis of either relapsed/refractory ALL/AML or secondary AML -Chemotherapy treatment in the 2 weeks before study entry. Granulocyte growth factor, leukapheresis and cranial irradiation should be discontinued at least 48 hours before the beginning of the protocol - Severe organ dysfunction, especially liver, kidneys, heart and lungs -Other concurrent severe disease that makes it inappropriate to enroll the patient in the study - History of a previous veno-occlusive disease (VOD) -Expected non-compliance to protocol schedule or unable to have regular follow-up due to psychological, social, familial reasons -Hypersensitivity to cytarabine, clofarabine, liposomal daunorubicin -Concomitant administration of any other experimental drug under investigation, or concurrent treatment with any other anti-cancer therapy other than specified in the protocol is not allowed -Pregnant or lactating patients
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: 66 days since the beginning of therapy;Main Objective: EVALUATION OF EFFICACY OF CLOFARABINE IN COMBINATION WITH CYTARABINE AND LIPOSOMAL DOXORUBICIN IN CHILDREN WITH RELAPSED/REFRACTORY ACUTE EITHER LYMPHOBLASTIC OR MYELOID ACUTE LEUKEMIA AND SECONDARY ACUTE MYELOID LEUKEMIA;Secondary Objective: safety and tolerability of clofarabine in combination with cytarabine and liposomal doxorubicin in children with relapsed/refractory acute either lynphoblastic or myeloid acute leukemia and secondary acute myeloid leukemia;Primary end point(s): -Overall Response Rate (ORR) = CR+CRi+PR= Complete Remission+ Complete Remission without either platelets or neutrophils recovery without blasts+ Partial Remission -Complete Remission Rate (CR+Cri) -Partial Remission Rate (RP)
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1)EFS (Event Free Survival), PFS (Progression Free Survival) and OS (Overall Survival) 2)Incidence of adverse grade = 3 events (NCI CTAE version 4.0) excluding nausea and vomit 3)Number of patients who will proceed to HSCT;Timepoint(s) of evaluation of this end point: 1) 12 and 18 months since the beginning of therapy 2)-3) Until HSCT