High risk leukaemia paediatric patients who would receive an haploidentical HSCT to be cured
Conditions
Interventions
Product Name: NK Cells stimulated with IL-15
Product Code: PF-007
Pharmaceutical Form: Injection
INN or Proposed INN: NK cells diferenciated adult allogeneic haploidentical ofexpanded periferic blood
Sponsors
Fundacion de investigacion Biomedica Hospital Universitario la Paz (FIBHULP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients of both genders with age = 21 years. 2. Not having an identical HLA donor (family or not) available in the time necessary for the donation of hematopoietic parents. 3. Have disposition of a haploidentical donor. 4. Diagnosis of high-risk hematologic malignancy. This includes: i. High-risk of acute lymphoblastic leukemia in first complete remission (CR1); ii. acute lymphoblastic leukemia in second complete remission (CR2); iii. acute lymphoblastic leukemia in third complete remission (CR3) or later; iv. High risk acute myeloid leukemia in CR1; v. acute myeloid leukemia in CR2 or later; vi. Relapsed acute myeloid leukemia with 12 months; viii Primary or secondary myelodysplastic syndrome; ix. NK cell leukemia, biphenotypic or undifferentiated in CR1 or later, x. Chronic myeloid leukemia (CML) in accelerated phase, in chronic phase with persistent molecular positivity, or with intolerance to tyrosine kinase inhibitors; xi. Hodgkin lymphoma in CR2 or later after autologous TPH failure, or unable to mobilize hematopoietic progenitors for autologous TPH; xii. Non-Hodgkin lymphoma in CR2 or later after autologous TPH failure, or unable to mobilize hematopoietic progenitors for autologous TPH; xiii. Juvenile myelomonocytic leukemia. 5. Evaluation prior to positive transplantation: I. Left ventricular ejection fraction> 40% or shortening fraction = 25%; ii) Creatinine clearance (ACr) or glomerular filtration rate (GFR) = 50 ml / min / 1.73 m2; iii) Forced vital capacity (FVC) = 50% of the predicted value or pulse-oximetry = 92% if the patient cannot perform lung function tests; iv. Karnofsky or Lansky index (probabilities of the patient's age) = 50; v. Bilirubin = 3 times the upper limit of normal for age; vi. Alanine aminotransferase (ALT) = 5 times the upper limit of normal for age. vii. Women who are not breastfeeding. viii No bacterial, fungal or viral infections not controlled at the time of inclusion. 6. Women with childbearing capacity must have a negative serum or urine pregnancy test performed within 14 days prior to inclusion in the trial and must agree to use highly specific contraceptive methods (diaphragms plus spermicide or male preservative plus spermicide , oral contraceptive combined with a second method of contraceptive implant, injectable contraceptive, permanent intrauterine device, sexual abstinence or partner with vasectomy) during their participation in the study and in the 30 days following the last visit of the trial. In the case of patients, men with reproductive capacity can commit to using a suitable barrier method for the duration of the study and up to 6 months later. Are the trial subjects under 18? yes Number of subjects for this age range: 18 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Patients with active infectious process or other serious underlying medical condition. 2. Patients who, according to the investigator's criteria, have a history of poor therapeutic compliance. 3. Patients who after a psychosocial evaluation are advised as not suitable for the procedure: • Socio-family situation that prevents the correct participation in the study. • Patients with emotional or psychological problems secondary to the disease such as post-traumatic stress disorder, phobias, delusions, psychosis, requiring support by specialists. • Evaluation of the involvement of family members in the patient's health. 4. Impossibility of understanding information about the trial. 5. Having received a research drug during the 30 days prior to the start of therapy or being within 5 half-lives of receiving a research drug, whichever is longer.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety, tolerability and the dose-limiting toxicities (DLT) of a single infusion of alloreactive or IL-15 ex-vivo activated Natural Killer cell after Haploidentical Stem Cell Transplantation. As co-primary objective we monitorize immune reconstitution including NK cell subsets, and NK cell cytotoxicity during the first year after HSCT. ;Secondary Objective: 1. To determine the efficacy of post haploTPH NK cell therapy, comparing it with the historical cohort recently reported by the GETH / GETMON. 2. Compare the clinical evolution of patients with the historical cohort recently reported by the GETH / GETMON. 3. Monitor immune reconstitution and characterize NK cells in patients, at the phenotypic and functional level, for 1 year after haploTPH. ;Primary end point(s): Toxicity. In order to determine the safety, each patient will be monitored for possible adverse effects. For its assessment, CTCAE v5.0 in the NCI will be followed and the proportion of patients presenting toxicity based on grade will be determined. Toxic effects that cannot be classified according to the criteria for the toxicity of said system, will be classified as follows (MedDRA classification): -Mild (asymptomatic) -Moderate (symptomatic but not significantly interfering with the function) -Severe (causes significant function interference) -Threatening to life ;Timepoint(s) of evaluation of this end point: 36moths | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The efficacy of post haploTPH NK cell therapy will be determined, comparing it with the historical cohort recently reported by GETH / GETMON in the incidence of: -Graft failure. -Acute / chronic GVHD -Viral reactivations (CMV, EBV, HHV-6, adenovirus, BKV). -Transplant related mortality (TRM). -Relapse of leukemia. The clinical evolution of the patients will be compared according to: • The dose of infused NK cells. • NK KIR match vs KIR mismatch cells. • The expansion, chimerism and phenotypic and functional characteristics of the infused NK. • The speed and characteristics of post haploTPH immune reconstitution. Monitor immune reconstitution by quantifying immunoglobulins at different times, and characterize NK cells in patients, at the phenotypic and functional level, for 1 year after haploTPH. ;Timepoint(s) of evaluation of this end point: 36Months | — |
Countries
Spain
Contacts
Public ContactIrene Garcia
UCICEC
Outcome results
None listed