NK cells stimulated ex vivo with IL-15Alloreactive NK cells
NK cells stimulated ex vivo with IL-15: When patient and donor are KIR-HLA match, the patient submits all HLA class I molecules, or in the absence of any, your donor does not have this molecule, or having it lacks the corresponding KIR receiver. For more information detailed information on the product under investigation, reference is made to the Dossier of the Research Product (IMPD): PEI 09-008
Alloreactive NK cells: When the patient lacks the HLA class I molecule and his donor has this molecule and also the donor NK cells have the KIR receptor that recognizes the absence of the corresponding HLA class I ligand
Study summary
Phase I / II study on infusion of alloreactive or stimulated Natural Killer cells with IL-15 ex vivo after haploidentical transplantation of hematopoietic progenitors in pediatric patients with hematologic malignancies (PHINK
Eligibility
Sex
ALL
Min age
—
Max age
21 Years
Healthy volunteers
No
Inclusion Criteria:
* Patients of both sexes with age ≤ 21 years.
* Not having an identical HLA donor (family or non-family) available in the time needed for the donation of hematopoietic parents.
* Having a haploidenic donor available
* Diagnosis of high-risk hematological malignancy. This includes:
* i. High risk ALL in first complete remission (RC1);
* ii. ALL in second complete remission (RC2);
* iii. ALL in third complete remission (RC3) or later;
* iv. High risk AML in RC1;
* v. AML in RC2 or later;
* vi. Relapsed AML with \<25% blasts in bone marrow;
* vii. AML related to previous treatments in CR\> 12 months;
* viii. Primary or secondary myelodysplastic syndrome
* ix. NK cell leukemia, biphenotypic or undifferentiated in RC1 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's lymphoma in RC2 or later after failure of autologous TPH, or unable to mobilize hematopoietic progenitors for autologous TPH
* xii. Non-Hodgkin's lymphoma in RC2 or later after failure of autologous TPH, or unable to mobilize hematopoietic progenitors for autologous TPH
* xiii. Myelomonocytic juvenile leukemia.
* Positive pre-transplant evaluation
* i. Left ventricular ejection fraction \> 40% or shortening fraction ≥ 25%;
* ii. Creatinine clearance (ACr) or glomerular filtration rate (TFG) ≥ 50 ml/min/1.73 m2
* iii. Forced Vital Capacity (FVC) ≥ 50% of predicted value or pulse-oximetry ≥ 92% if the patient cannot perform the pulmonary function tests;
* iv. Karnofsky or Lansky Index (depending on 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 uncontrolled bacterial, fungal, or viral infections at the time of inclusion.
* Women of childbearing potential must have a negative serum or urine pregnancy test performed within 14 days prior to trial inclusion and must agree to use highly effective contraceptive methods (diaphragms plus spermicide or male condom plus spermicide, oral contraceptive combined with a second method of contraceptive implant, injectable contraceptive, permanent intrauterine device, sexual abstinence, or partner with vasectomy) during study participation and for six months after the last trial visit. In the case of male patients with reproductive capacity, they must commit to using an appropriate barrier method for the duration of the study and for up to 6 months thereafter
Exclusion Criteria:
* Patients with an active infectious process or other serious underlying medical condition
* Patients who, according to the investigator's criteria, have a history of poor compliance with therapy.
* Patients who after a psycho-social evaluation are advised as not suitable for the procedure:
* i. Social-family situation that makes correct participation in the study impossible.
* ii. Patients with emotional or psychological problems secondary to the illness such as post-traumatic stress disorder, phobias, delusions, psychosis, with the need for support from specialists.
* iii. Evaluation of the involvement of family members in the health of the patient
* Inability to understand the information about the trial
* Received an investigational drug within 30 days prior to the start of therapy or within 5 half-lives of receiving an investigational drug, whichever is longer.
Primary outcome measure(s)
Dose-limiting toxicity (TLD) — 52 weeks To determine dose-limiting toxicity (TLD) of a single infusion of aloreactive NK cells or ex vivo IL-15-stimulated NK cells after haploTPH in pediatric patients with high-risk leukemias.
Maximum tolerated dose (MTD) — 52 weeks To determine maximum tolerated dose (MTD) of a single infusion of aloreactive NK cells or ex vivo IL-15-stimulated NK cells after haploTPH in pediatric patients with high-risk leukemias.
Trial sites (10)
Facility
City
Region
Status
Hospital Clínico Universitario de Santiago
Santiago de Compostela
A Coruña
Hospital Universitario Central de Asturias
Oviedo
Principality of Asturias
Hospital de la Santa Creu i Sant Pau
Barcelona
Spain
Hospital General Universitario Gregorio Marañón
Madrid
Spain
Hospital Infantil Universitario Niño Jeús
Madrid
Spain
Hospital Universitario La Paz
Madrid
Spain
Hospital Regional Universitario de Málaga (Carlos de Haya)
Málaga
Spain
Hospital Clínico Universitario Virgen de la Arrixaca
Murcia
Spain
Hospital Universitario Virgen del Rocío
Seville
Spain
Hospital Universitario La Fe
Valencia
Spain
More Instituto de Investigación Hospital Universitario La Paz trials in Spain
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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