UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Prophylactic infusion of NK cell and gamma/delta chain positive T cell from transplantation donor for poor prognostic or refractory hematologic malignancy and solid tumor -Ibaraki Children's Hospital phase II study
Title of the study (Brief title)	ICH-NKDLI-16
Region	Japan

Condition
Condition	Acute leukemia, malignant lymphoma, and solid tumor
Classification by specialty	Hematology and clinical oncology Pediatrics Child
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To evaluate the safety and efficacy of preventive infusion of donor NK cell and TCR gamma delta chain positive T cell for refractory hematologic malignancy and solid tumor in an attempt to improve the prognosis
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	Disease free survival rate at 1 year after infusion
Key secondary outcomes

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Historical
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Device,equipment
Interventions/Control_1	Patients who have undergone peripheral blood stem cell transplantation or bone marrow transplantation from HLA-4/8 to 6/8 matched family member for unfavorable hematologic or solid malignant neoplasm are eligible. On day+60 or more after transplant when the patients have no or grade 1 acute GVHD, peripheral blood mononuclear cells are collected from the same donor using Spectra Optia Apheresis System (Terumo BCT, Inc., Lakewood, Colorado, USA). The mononuclear cells collected were submitted to magnetic labeling and depletion of TCR alpha/beta positive T-cells and CD19 positive B-cells employing CliniMACS System (Miltenyi Biotec GmbH, Bergisch Gladbach, Germany) and CliniMACS TCR alpha/beta-Biotin Reagent System and CD19 Reagent System. The purified NK-cells and TCR gamma/delta positive T-cells are analyzed by flowcytometry and infused to the patients. The patients undergo physical examination, peripheral blood investigation, bone marrow analysis, and imaging study serially on day +30, +60, +90, +180, +360, +720 after infusion to investigate chimerism, engraftment, immunological recovery, disease condition, or side effect.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	0 years-old <=
Age-upper limit	20 years-old >
Gender	Male and Female
Key inclusion criteria	(1)Histologically or cytologically diagnosed acute leukemia, or malignant lymphoma, or solid tumor (2)Age less than 20 years at diagnosis (3)Confirmed Eligible clinical entity (3-1)High Risk acute leukemia or malignant lymphoma (a)Primary induction failure at transplantation (b)In the first complete remission obtained after more than three courses of induction (c)In the first complete remission with detectable minimum residual disease (d)In the first complete remission with unfavorable cytogenetic or molecular features (e)Very early relapse within three years after diagnosis, the second complete remission but poor response or minimum residual disease against re-induction chemotherapy after relapse, the third or more advanced complete remission or not in remission after relapse (3-2)High risk solid tumor (a)MYCN-amplified, 1p-lost, or 11q-lost neuroblastoma (b)Not in remission (3-3)No HLA-match donor in family and no appropriate donor in unrelated donor bank or cord blood bank (3-4)Recurrent acute leukemia or malignant lymphoma after hematopoietic stem cell transplantation (3-5)Recurrent solid tumor (4)ECOG performance status score 0-1, if deterioration due to active disease, score 2 eligible (5)Appropriate organ function fulfilling following condition a)Serum concentration of total bilirubin, less than upper limit of normal range for age b)Serum concentration of creatinine, less than upper limit of normal range for age c)Serum concentration of cystatin C, less than 1.00 mg/L d)Pulse-oximetry saturation more than 97 percent awake and at rest breathing room air e)%Vital capacity, more than 70% by pulmonary function test (if patient more than 6 years old) f)Forced expiratory volume in 1 second%, more than 70% (if patient more than 6 years old) g)Plasma BNP, less than 40 pg/mL h)%Fractional shortening, more than 27% (6)All patients and/or their parents or legal guardians must sign a written informed consent
Key exclusion criteria	(1)Germ line chromosomal abnormality other than trisomy 21 (2)Concurrent or prior malignant disease other than the original disease in interest or prior organ transplantation other than hematopoietic cell transplantation (3)Congenital or acquired immunodeficiency (4)Uncontrolled fungal, bacterial, or viral infection (including tuberculosis of HIV) (5)Pregnant, lactating, or highly suspected to be pregnant (6)Corrected QT interval by Fridericia, more than 0.45 second (7)Active hemorrhage in central nervous system, fulfilling grade more than 3 on CTCAE version 4.0 (8)Consciousness disturbance, score less than 14 on Glasgow Coma Scale (9)Obesity, by more than 30% of average weight for age. (10)Considered to be unsuitable for entry for the study
Target sample size	10

Research contact person
Name of lead principal investigator	Keisuke Kato, M.D.
Organization	Ibaraki Children's Hospital
Division name	Division of Pediatric Hematology and Oncology, Specialty Care Service, Pediatrics
Address	Futaba-dai 3-3-1, Mito, Japan
TEL	029-254-1151
Email	keikato-ind@umin.ac.jp

Public contact
Name of contact person	Keisuke Kato, M.D.
Organization	Ibaraki Children's Hospital
Division name	Division of Pediatric Hematology and Oncology, Specialty Care Service, Pediatrics
Address	Futaba-dai 3-3-1, Mito, Japan
TEL	029-254-1151
Homepage URL
Email	keikato-ind@umin.ac.jp

Sponsor
Institute	Ibaraki Children's Hospital
Institute
Department

Funding Source
Organization	Ibaraki Children's Hospital
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2017 Year 07 Month 28 Day

Progress
Recruitment status	Enrolling by invitation
Date of protocol fixation	2017 Year 07 Month 28 Day
Anticipated trial start date	2017 Year 07 Month 28 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2017 Year 07 Month 25 Day
Last modified on	2017 Year 09 Month 17 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030970