Leukemia relapse prevention given haploidentical hematopoietic stem cell transplantation MedDRA version: 21.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10000844 Term: Acute lymphoblastic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: linfociti T citotossici anti-leucemia
Product Code: [CTL anti-leucemia]
Pharmaceutical Form: Suspension for injection
Current Sponsor code: ND
Concentration unit: IU/kg international uni
Sponsors
FONDAZIONE I.R.C.C.S. POLICLINICO SAN MATTEO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age inferior or equal to 18 years and superior or equal to 1 months 2) Life expectancy > 12 weeks 3) Patients affected by life-threatening acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) with high risk of relapse after HSCT, namely: Patients affected by ALL: - in first morphological remission but with a positive minimal residual disease = 1 x 10-3 before HSCT; - in second morphological remission after a high-risk relapse (patients belonging to the S3-S4 BFM risk group), independently of the level of minimal residual disease; - in second morphological remission with any positivity of minimal residual disease before HSCT; - in third or subsequent morphological remission, independently of the level of minimal residual disease; - patients not in morphological remission at time of HSCT. Patients affected by AML: - in first morphological remission and with a flow cytometry MRD at the end of induction therapy = 0.1%; - in first morphological remission and with high-risk disease according to cytogenetics aberrations; - in first morphological remission after a primary induction failure; - in second morphological remission; - in third or subsequent morphological remission; - patients not in morphological remission at time of HSCT. 4) Pre-HSCT Lansky / Karnofsky score = 40%. 5) HIV negativity. 6) Written informed consent signed by the parents or legal guardians (in case of patients =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Ongoing active superior or equal to grade II acute GvHD or chronic extensive GvHD due to a previous allograft 2) Current clinically active infectious disease (including positive HIV serology or viral RNA) 3) Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction 3 times ULN) 5) Renal dysfunction: serum creatinine > 1.5 times ULN or calculated creatinine clearance < 60 ml/min/1.73 m2 6) End stage irreversible multi-system organ failure. 7) Other active malignancy. 8) Pregnant or breast feeding female patient 9) Lack of parents’/guardian’s written informed consent for minors or lack of written informed consent for patients aged 18 y.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective will be safety, evaluated as the incidence of acute GVHD. Acute GVHD will be diagnosed and graded according to the NIH criteria. Grade II-IV acute GVHD will be expressed as cumulative incidence (CI) considering disease relapse and death in remission without GVHD as competing events. A CI of acute GVHD = 25% will be considered as acceptable treatment toxicity.;Secondary Objective: Relapse (REL): REL, defined as the time from HSCT to the date of disease relapse will be calculated at 3, 6, 9, 12 18 and 24 months after HSCT and expressed as CI considering death in remission as a competing event. The CI of REL in treated patients will be compared with that of recipients of haplo-HSCT with the same disease characteristics and prognosis, give conventional infusions of unmanipulated, donor-derived T lymphocytes (DLI). Preliminary efficacy of the treatment will be a CI of REL = of the CI of REL observed in the control group. Other secondary objectives: 1. Non-relapse mortality (NRM) will be calculated at 3, 6, 9, 12 18 and 24 months after HSCT. 2. Overall survival (OS) will be calculated at 3, 6, 9, 12 18 and 24 months after HSCT. 3. Event-free survival (EFS) will be calculated at 3, 6, 9, 12 18 and 24 months after HSCT. 4. Event-free and chronic GVHD-free survival will be calculated at 3, 6, 9, 12 18 and 24 months after HSCT. 5. Infectious complications. ...;Primary end point(s): Acute GVHD;Timepoint(s) of evaluation of this end point: Incidence of acute GVHD | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Disease relapse;Timepoint(s) of evaluation of this end point: The time from HSCT to the date of disease relapse | — |
Countries
Italy
Contacts
Public ContactEmatologia - Oncoematologia Pediatr
Fondazione IRCCS Policlinico San Matteo
Outcome results
None listed