UMIN-CTR Clinical Trial

Public title

Feasibility and pharmacokinetic study of ch14.18 immunotherapy using teceleukin and CSF (mirimostim, filgrastim) for neuroblastoma

Acronym

Feasibility and pharmacokinetic study of ch14.18 immunotherapy for neuroblastoma

Scientific Title

Feasibility and pharmacokinetic study of ch14.18 immunotherapy using teceleukin and CSF (mirimostim, filgrastim) for neuroblastoma

Scientific Title:Acronym

Feasibility and pharmacokinetic study of ch14.18 immunotherapy for neuroblastoma

Region

Japan

Condition

intractable neuroblastoma

Classification by specialty

Pediatrics

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To investigate feasibility of ch14.18 with teceleukin and M-CSF (M regimen) or GCSF (G regimen)

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase I,II

Primary outcomes

DLT of ch14.18, teceleukin, mirimositim, filgramostim (phaseI)
Proportion of completing 5 courses of M regimen and G regimen (phaseIIa)

Key secondary outcomes

1. adverse events profile
2. clinical benefit rate. response rate. progression free survival. disease free survival. overall survival.
3. pharmacokinetics and dose-response for ch14.18 and teceleukin
4. antibody dependent cell-mediated cytotoxicity activity
5. anti-chimera antibody response proportion

Study type

Interventional

Basic design

Parallel

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Treatment M
CSF regimen (ch14.18 10-20h div d4-7, mirimostim 2h div d1-14) and IL2 regimen (ch14.18 10-20h div d8-11, teceleukin 24h div d1-4, d8-11) are performed alternately, starting CSF regimen upto 5 courses

Interventions/Control_2

Treatment G
CSF regimen (ch14.18 10-20h div d4-7, filgrastim s.c. d1-14) and IL2 regimen (ch14.18 10-20h div d8-11, teceleukin 24h div d1-4, d8-11) are performed alternately, starting CSF regimen upto 5 courses.

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

2

years-old

<=

Age-upper limit

45

years-old

>=

Gender

Male and Female

Key inclusion criteria

1. Histogically proven neuroblastoma
2. Prior history of high-dose chemotherapy (HDC).
3. (phaseI): B. is required.
(phaseIIa): A. or B. is required.
A. No prior chemotherapy after HDC, 180 days or less after stem-cell transplantation and none of the followings: radiologically confirmed progressive disease, moderate bone marrow invasion, or, high urine HVA or VMA concentration
B. One or more prior chemotherapy after HDC and at least one of the followings: one and more radiologically confirmed progressive site(s), bone marrow invasion, high urine HVA or VMA concentration, and tumor associated symptom(s)
4. PS(Lansky or Karnofsky) >= 50%
5. If the last chemotherapy contains one or more drugs with hematologic dose limiting toxicity (DLT),
7 days or more have passed since last use of anti-tumor agents which are administerd protractedly and 14 days or more have passed since last use of anti-tumor agents which are not administered in protracted way.
6. 7 days or more have passed since last chemotherapy which does not contain any drugs with hematologic DLTs
7. No prior irradiation within 14 days if radiation fields is limited.
No prior irradiation within 3 months if radiation fields contain either whole brain and spine, whole abdomen, whole lung, whole body, or more than 50% of pelvis.
No prior irradiation within 6 weeks if radiation fields contain either less than 50% of pelvis, or 5 or less vertebras.
8. No prior allogeneic hematopoietic stem cell transplantation
9. Normal organ function confirmed by laboratory tests within 14 days
10. No intracranial hemorrhagic episode within one week and platelet count >= 50000/ul and Hb >= 8.0g/dl more than three days after last blood transfution.
11. Written informed consent from patient and/or legal guardian

Key exclusion criteria

1. Active double cancer(synchronous
double cancer and metachronous
double cancer within 5 disease
-free years),excluding carcinoma
In situ(lesions equal to
Intraepithelial or intramucosal
Cancer)judged to have been cured
with local treatment.
2. Active infection requiring
systemic medication.
3. 14 days or less after last administration of systemic steroids
4. 28 days or less after last administration of immunogloblin
5. Any abnormalities in electrocardiogram
tested within 28 days,which require
intervention.
6. Fractional Shortning < 30% or Ejection Fraction < 55% by echocargiogram within 28 days.
7. Respiratory or heart disorder requiring oxygen supply
8. Possibilly/confirmed pregnant or lactating
9. Impossible for sexually active patients to use one of effective methods of birth control during and 6 month after treatment
10. Psychosis which is not appropriate for participating in this study.
11. allergy or predisposition for
any elements involved in all the investigational agents in this study

Target sample size

25

Name of lead principal investigator

1st name
Middle name
Last name	Junichi Hara

Organization

Osaka City General Hospital

Division name

Pediatric Hematology and Oncology department

Zip code

Address

2-13-22 Miyakojima-hondori Miyakojima-ku, Osaka 534-0021 JAPAN

TEL

06-6929-1221

Email

j-hara@hospital.city.osaka.jp

Name of contact person

1st name
Middle name
Last name	Hiroshi Kawamoto

Organization

National Cancer Research Center

Division name

Division of Pediatric Oncology

Zip code

Address

5-1-1 Tsukiji, Chuo-ku, Tokyo

TEL

03-3542-2511

Homepage URL

Email

shoni@ml.res.ncc.go.jp

Institute

A study group for "Research on Applying Health Technology" of health and Labor Sciences Research Grants

Institute

Department

Personal name

Organization

Ministry of Health,Labour and
Welfare

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan

Co-sponsor

investigational agent suppliers:
OHARA Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Shionogi & Co., Ltd., Japan Chemical Research Pharmaceutical Co., Ltd.

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

大阪市立総合医療センター（大阪府）、国立がん研究センター中央病院（東京都）

Date of disclosure of the study information

2013

Year

10

Month

09

Day

URL releasing protocol

Publication of results

Partially published

URL related to results and publications

http://meeting.ascopubs.org/cgi/content/abstract/33/15_suppl/e21018?sid=9c9f82cd-3837-4b90-9279-406e

Number of participants that the trial has enrolled

Results

Sixteen (8 each in R1 and R2) recurrent pts were enrolled. All two DLT (Grade4 thrombocytopenia, Grade3 hypokalemia) of 12 pts in pI occurred only on IL2 regimen (IL2:level0, ch14.18: level1). The recommended dose (RD) of IL2 was level0 (0.75 million IU/m2 (d1-4) and 1 million IU/m2 (d8-11)). the RDs of All the other agents were determined at level1 (Dmab:17.5mg/m2, M-CSF: 6 million IU/m2, G-CSF: 5 ug/kg). SAE were 3 blood stream infections, 1 Grade 3 pancreatitis (inflammation around metastatic lesion in pancreas), 2 upper respiratory infection and 1 Grade4 transaminitis. 7/8 in R1 and 5/8 in R2 completed more than 5 cycles. All eleven consented pts recieved 7 cycles. The result of PK analysis is presented in the following table. Augmentation of ADCC was confirmed in both R1 and R2. More than half pts were positive for HACA assay.

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

No longer recruiting

Date of protocol fixation

2012

Year

12

Month

26

Day

Date of IRB

Anticipated trial start date

2013

Year

10

Month

15

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2013

Year

10

Month

09

Day

Last modified on

2016

Year

04

Month

11

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013996