UMIN-CTR Clinical Trial

Public title

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

Acronym

ICH-NKDLI-16

Scientific Title

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

Scientific Title:Acronym

ICH-NKDLI-16

Region

Japan

Condition

Acute leukemia, malignant lymphoma, and solid tumor

Classification by specialty

Hematology and clinical oncology	Pediatrics	Child

Classification by malignancy

Malignancy

Genomic information

YES

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

Primary outcomes

Disease free survival rate at 1 year after infusion

Key secondary outcomes

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Historical

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Keisuke Kato, M.D.

Organization

Ibaraki Children's Hospital

Division name

Division of Pediatric Hematology and Oncology, Specialty Care Service, Pediatrics

Zip code

Address

Futaba-dai 3-3-1, Mito, Japan

TEL

029-254-1151

Email

keikato-ind@umin.ac.jp

Name of contact person

1st name
Middle name
Last name	Keisuke Kato, M.D.

Organization

Ibaraki Children's Hospital

Division name

Division of Pediatric Hematology and Oncology, Specialty Care Service, Pediatrics

Zip code

Address

Futaba-dai 3-3-1, Mito, Japan

TEL

029-254-1151

Homepage URL

Email

keikato-ind@umin.ac.jp

Institute

Ibaraki Children's Hospital

Institute

Department

Personal name

Organization

Ibaraki Children's Hospital

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2017

Year

07

Month

28

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Enrolling by invitation

Date of protocol fixation

2017

Year

07

Month

28

Day

Date of IRB

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

Other related information

Registered date

2017

Year

07

Month

25

Day

Last modified on

2017

Year

09

Month

17

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030970