UMIN-CTR Clinical Trial

Basic information
Public title	Phase 2b study of combined immunotherapy with dinutuximab, interleukin-2, and G-CSF for high risk neuroblastoma
Acronym	GD2-P2
Scientific Title	Phase 2b study of combined immunotherapy with dinutuximab, interleukin-2, and G-CSF for high risk neuroblastoma
Scientific Title:Acronym	GD2-P2
Region	Japan

Condition
Condition	high risk neuroblastoma
Classification by specialty	Hematology and clinical oncology Pediatrics
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the effiicacy of Japan regimen (G therapy) combining dinutuximab, teceleukin and filgrastim, compared to the US regimen combining dinutuximab, aldesleukin, sargramositim and isotretinoin as maintenance therapy for high risk neuroblastoma
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Two-year event free survival
Key secondary outcomes	1. Overall-survival, response rate and progression-free survival 2. Adverse event of G therapy and US regimen 3. ADCC activity in G therapy and US regimen 4. Production rate of human anti-chimeric antibody (HACA) 5. Pharmacokinetics of isotretinoin

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	G therapy: Six courses of G therapy CSF regimen and G therapy IL2 regimen alternately. 1. G therapy CSF regimen Subcutaneous injection of filgrastim 5 mcrg / kg from day 1 to day 14. Intravenous administration of dinutuximab 17.5 mg / m2 from day 4 to day 7. 2. G therapy IL2 regimen Intravenous administration of teceleukin 75 MU / m2 from day 1 to day 4 and from day 8 to day 11 Intravenous administration of dinutuximab 17.5 mg / m2 from day 4 to day 7
Interventions/Control_2	US regimen: Five courses of US CSF regimen and US IL2 regimen alternately then one course of isotretinoin alone. 1. US CSF regimen Subcutaneous injection of sargramostim 250 mcrg / kg from day 1 to day 14. Intravenous administration of dinutuximab 17.5 mg / m2 from day 4 to day 7. Orally 160 mg/m2 (BW >12 kg) or 5.33 mg/kg (BW <=12 kg) isotretionoin from day 11 to day 24 2. US IL2 regimen Intravenous administration of aldesleukin 300 MU / m2 from day 1 to day 4 and from day 8 to day 11 Intravenous administration of dinutuximab 17.5 mg / m2 from day 4 to day 7 Orally 160 mg/m2 (BW >12 kg) or 5.33 mg/kg (BW <=12 kg) isotretionoin from day 11 to day 24 3. Isotretinoin regimen Orally 160 mg/m2 (BW >12 kg) or 5.33 mg/kg (BW <=12 kg) isotretionoin from day 11 to day 24
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	Not applicable
Age-upper limit	31 years-old >
Gender	Male and Female
Key inclusion criteria	1. All patients must have completed therapy including intensive induction followed by ASCT and radiotherapy. 2. No more than 12 months from the date of starting the first induction chemotherapy after diagnosis to the date of ASCT. 3. At pre-ASCT evaluation patients must meet the INRC for CR, VGPR, or PR for any region. 4. For those with residual disease after operation, re-evaluation of irradiated residual tumors is performed at the earliest 5 days after completing radiotherapy. 5. <= 10% tumor seen on any specimen from a bone marrow aspirate/biopsy. 6. Patients must be enrolled no later than Day 100 after PBSC infusion. However, in the cases with surgery followed by autologous peripheral blood transfusion, allowing less than 150 days from autologous peripheral blood stem cell infusion. 7. Patients must not have received prior anti-GD2 antibody therapy. 8. Patients must have a Lansky or Karnofsky Performance Scale score of >= 50%. 9. Patient must have adequate organ function.
Key exclusion criteria	1. Synchronous or asynchronous (within 5 years) other cancer except carcinoma in situ or intramucosal carcinoma. 2. Active infection requires systemic therapy. 3. Epileptic seizures without control by anticonvulsants 4. Daily use of a steroid 5. Administration of immune globulin within 28 days 6. Abnormalities of ECG requires therapy. 7. Less than 30% of Fractional Shortening and less than 55% of Ejection Fraction in cardiac function within 28 days There is respiratory failure requiring 8. oxygen administration 9. Woman during pregnancy, or impossible to discontinue breast-feeding for 120 days after the final dose of study treatment. 10. Patient or the partner without intent to use birth control. 11. Inadequate physical condition judged by investigator. 12. Known investigational drugs allergy.
Target sample size	34

Research contact person
Name of lead principal investigator	1st name Junichi Middle name Last name Hara
Organization	Osaka City General Hospital
Division name	Department of Pediatric Hematology/Oncology
Zip code	5340021
Address	2-13-22, Miyakojimahondori, Miyakojima-ku, Osaka
TEL	06-6929-1221
Email	j-hara@med.osakacity-hp.or.jp

Public contact
Name of contact person	1st name Chika Middle name Last name Nitani
Organization	Osaka City General Hospital
Division name	Department of Pediatric Hematology/Oncology
Zip code	5340021
Address	2-13-22, Miyakojimahondori, Miyakojima-ku, Osaka
TEL	06-6929-1221
Homepage URL
Email	c-tanaka@med.osakacity-hp.or.jp

Sponsor
Institute	Osaka City General Hospital
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

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

IRB Contact (For public release)
Organization	Clinical Research Ethics Committee of Osaka City General Hospital
Address	2-13-22, Miyakojimahondori, Miyakojima-ku, Osaka
Tel	06-6929-1221
Email	c-tanaka@med.osakacity-hp.or.jp

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	大阪市立総合医療センター（大阪府）、北海道大学病院（北海道）、九州大学病院（福岡県）、広島大学病院（広島県）、成育医療研究センター（東京都）、東京都立小児医療センター（東京都）

Other administrative information
Date of disclosure of the study information	2016 Year 07 Month 04 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	35
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

Progress
Recruitment status	Completed
Date of protocol fixation	2016 Year 05 Month 09 Day
Date of IRB	2016 Year 05 Month 20 Day
Anticipated trial start date	2016 Year 07 Month 04 Day
Last follow-up date	2019 Year 10 Month 04 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2016 Year 07 Month 04 Day
Last modified on	2020 Year 02 Month 04 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000026438