UMIN-CTR Clinical Trial

Basic information
Public title	A Phase II study of combination chemotherapy including Bortezomib in pediatric patients with relapsed acute lymphoblastic leukemia (Investigator-initiated clinical trial)
Acronym	Bortezomib for relapsed ALL (BZM-ALL-2)
Scientific Title	A Phase II study of combination chemotherapy including Bortezomib in pediatric patients with relapsed acute lymphoblastic leukemia (Investigator-initiated clinical trial)
Scientific Title:Acronym	Bortezomib for relapsed ALL (BZM-ALL-2)
Region	Japan

Condition
Condition	A high-risk group of pediatric patients with first relapse of ALLor refractory ALL (patients who develop 2nd or subsequent relapse, relapse after hematopoietic cell transplantation or fail to achieve remission induction with one or more therapies).
Classification by specialty	Hematology and clinical oncology Pediatrics
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the efficacy of combination chemotherapy including Bortezomib (Investigational Ingredient Code: JNJ-26866138; Brand Name: Velcade; hereinafter referred to as "investigational product") (B-PVLDC-TIT) in a high-risk first relapse group of pediatric patients with acute lymphoblastic leukemia (ALL). To evaluate the efficacy for refractory ALL in expansion cohort.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	Remission induction rate at the end of remission induction therapy using B-PVLDC-TIT regimen
Key secondary outcomes	1) Minimal Residual Disease (MRD) at the end of remission induction therapy using B-PVLDC-TIT regimen 2) 4-month event-free survival, overall survival, MRD at 4-month , where events are defined as relapse and death. 3) Proportion of the patients in remission and MRD at the start of transplantation conditioning 4) Duration of remission 5) Profile of adverse events occurring up to Day 28 of combination chemotherapy period

Base
Study type	Interventional

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

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	In addition to the standardized induction therapy, intravenous administration of Bortezomib will be given at a dose of 1.3mg/m2 on Days 1, 4, 8, and 11.
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	Not applicable
Age-upper limit	19 years-old >=
Gender	Male and Female
Key inclusion criteria	1) Acute lymphoblastic leukemia (ALL), except mature B-cell ALL 2) First relapsed patients who are classified as high risk (S3 or S4) in the Risk Classification for First ALL Relapse In expansion cohort, patients who develop 2nd or subsequent relapse, relapse after hematopoietic cell transplantation or fail to achieve remission induction with one or more therapies. 3) Patients who were 17 years or younger at the first onset and 19 years or younger at relapse. In expansion cohort, patients who were 17 years or younger at the first onset and 19 years or younger at the time of informed consent. 4) ECOG Performance Status 0 to 2 5) The percentage of blast cells in the bone marrow is 5% or higher. 6) Patients who received the last chemotherapy for first-onset ALL 7 or more days before the day of enrollment, and who have not started treatment of relapsed ALL In expansion cohort, patients who received the last chemotherapy for ALL 7 or more days before the day of enrollment. 7) Without following previous histories/complications: Grade 2 or worse CNS or peripheral nerve disorder Deep mycosis, interstitial pneumonia, pulmonary fibrosis Hypersensitivity to mannitol, boron, or other components of the drugs in the trial regimen 8) Patients meeting the following requirements as indicated by laboratory tests within 14 days before enrollment: 1. SpO2 >=96% and chest CT indicating no abnormal finding in the lung fields 2. KL-6, SP-D, beta-D glucan, Candida antigen, and Aspergillosis antigen are within normal range 3. AST, ALT: <= 5x ULN 4. Serum bilirubin: <= 2.0mg/dL 5. Creatinine: <= 2x ULN 6. 12-lead ECG indicating no abnormality requiring treatment and/or no abnormal conducting system 9) Patients who can receive PSL monotherapy and combination therapy during hospitalization 10) Consent to participate in this study obtained from the subject's representative
Key exclusion criteria	1) Patients who received hematopoietic cell transplantation(only in high risk group of first relapse) 2) Patients who received allograft transplantation within 4 months(120 days) (only in expansion cohort) 3) Patients who received immunosuppressant within 14 days 4) Double cancer 5) Concurrent infection requiring systemic treatment at enrollment 6) Fever over 38.5 degrees Celsius 7) Pregnant or possibly pregnant women. Breastfeeding women. Men and women providing no consent to avoiding pregnancy during the study. 8) Determined as difficult to participate in the study because of complicated psychiatric disease or mental symptoms 9) The following complications or previous histories: Previous cardiac disease Patients with a history of continuous oxygen therapy required for treatment or a history of respiratory function impairment Patients with complications determined to seriously compromise conducting of the study (for example, uncontrollable diabetes) 10) CNS disorder 11) Down syndrome 12) Patients determined as ineligible for participation in the study by an investigator or a sub-investigator for other reasons
Target sample size	22

Research contact person
Name of lead principal investigator	1st name Middle name Last name Chitose Ogawa
Organization	National Cancer Center Hospital
Division name	Department of Pediatric Oncology
Zip code
Address	5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
TEL	03-3542-2511
Email	ncch-bzm@c-ctd.co.jp

Public contact
Name of contact person	1st name Middle name Last name Miwa Izutsu
Organization	CTD Inc.
Division name	-
Zip code
Address	3-3-2, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
TEL	03-6228-4878
Homepage URL
Email	ctd-bzm@c-ctd.co.jp

Sponsor
Institute	Department of Pediatric Oncology, National Cancer Center Hospital
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Government offices of other countries
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Janssen Pharmaceutical K.K.
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

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	国立がん研究センター中央病院（東京都）、神奈川県立こども医療センター（神奈川県）、 京都大学医学部附属病院（京都府）、福島県立医科大学附属病院（福島県）、名古屋医療センター（愛知県）、新潟県立がんセンター新潟病院（新潟県）、国立成育医療研究センター（東京都）、三重大学医学部附属病院（三重県）、兵庫県立こども病院（兵庫県）、大阪市立総合医療センター(大阪府)、広島大学病院（広島県）、九州がんセンター（福岡県）

Other administrative information
Date of disclosure of the study information	2016 Year 09 Month 09 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
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 07 Month 08 Day
Date of IRB	2016 Year 09 Month 05 Day
Anticipated trial start date	2016 Year 09 Month 21 Day
Last follow-up date	2020 Year 04 Month 30 Day
Date of closure to data entry	2020 Year 05 Month 31 Day
Date trial data considered complete	2020 Year 09 Month 30 Day
Date analysis concluded	2020 Year 11 Month 30 Day

Other
Other related information

Management information
Registered date	2016 Year 08 Month 29 Day
Last modified on	2021 Year 03 Month 31 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027309