UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A phase I study (investigator-initiated) on the safety and pharmacokinetics of Bortezomib with combination chemotherapy in pediatric and young adult patients with refractory acute lymphocytic leukemia
Title of the study (Brief title)	Bortezomib for relapsed ALL (BZM-ALL-1)
Region	Japan

Condition
Condition	Refractory acute lymphocytic leukemia(ALL) in children and young adults
Classification by specialty	Hematology and clinical oncology Pediatrics
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To determine the tolerability and safety of Bortezomib with combination chemotherapy in pediatric and young adult patients with refractory ALL, and evaluate the pharmacokinetics of Bortezomib administered concurrently. To evaluate complete remission as well as minimal residual disease (MRD) after induction therapy.
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase I

Assessment
Primary outcomes	Dose-limiting toxicity (DLT) Pharmacokinetics of Bortezomib
Key secondary outcomes	Complete remission(CR) after induction therapy Minimal residual disease after induction therapy

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 1.3 or 1.0 mg/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	1 years-old <=
Age-upper limit	29 years-old >=
Gender	Male and Female
Key inclusion criteria	1) 1-29 years old when obtaining consent. 2) Consent to participate in this study obtained from the subject or his/her representative. 3) Diagnosed with ALL 4) Patients meeting any one of the following requirements: 1. 1st bone marrow relapse within 36 months after the date of initial diagnosis of ALL 2. 2nd or subsequent bone marrow relapse 3. Bone marrow relapse after hematopoietic cell transplantation 4. Failure to achieve remission induction with one or more therapies 5) At least 7 days elapsed from the final dose of chemotherapy to the day of enrollment. 6) ECOG Performance Status 0 to 2 7) Patients meeting the following requirements as indicated by laboratory tests within 14 days before enrollment with sufficiently preserved liver, renal, and cardiac functions. 1. AST and ALT <= 5x ULN* 2. Serum bilirubin <= 2.0 mg/dL 3. Creatinine <= 2x ULN 4. 12-lead ECG indicating no abnormality requiring treatment and/or no abnormal conducting system. 8) SpO2 >= 96% and chest CT indicating no abnormal finding in the lung fields. 9) Patients who can receive PSL monotherapy and combination therapy during hospitalization. * Child-specific normal limit for patients younger than 18 years old and site-specific normal limit for patients aged 18 years or older
Key exclusion criteria	1) Mature B-cell ALL (L3) 2) Previous treatment with Bortezomib 3) The following complications/previous histories: 1. Concurrent infection requiring systemic treatment at enrollment. 2. Previous cardiac disease: previous myocardial infarction/angina pectoris within 12 months before enrollment. 3. Patients requiring oxygenation or showing respiratory insufficiency. 4. Previous interstitial pneumonia or pulmonary fibrosis. 5. Abnormal pulmonary function test, KL-6, SP-D, and SP-A as demonstrated by screening tests. 6. Abnormal beta-D glucan, Candida antigen, and Aspergillosis antigen as demonstrated by screening tests. 7. Previous deep fungus infection. 8. CNS or peripheral disorder. 9. Other complications determined to seriously compromise conducting of the study (for example, uncontrollable diabetes). 4) Down syndrome 5) Active double cancer (simultaneous double cancer, and metachronous double cancer with up to a 5-year disease-free period; carcinoma in situ determined as cured with local therapy or lesions consistent with intramucosal carcinoma are not included in double cancer.) 6) Determined as difficult to participate in the study because of complicated psychiatric disease or mental symptoms. 7) Participation in other clinical studies, excluding those of ALL, within 30 days after obtaining consent. 8) Pregnant or possibly pregnant women. Breastfeeding women. Men and women providing no consent to avoiding pregnancy during the study. 9) Previous hypersensitivity to mannitol, boron, or other components of Bortezomib. 10) Patients determined as ineligible for participation in the study by an investigator/sub-investigator for other reasons.
Target sample size	3

Research contact person
Name of lead principal investigator	Chitose Ogawa
Organization	National Cancer Center Hospital
Division name	Department of Pediatric Oncology
Address	5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
TEL	03-3542-2511
Email	chitoseo@qb3.so-net.ne.jp

Public contact
Name of contact person	Yutaka Ito
Organization	National Hospital Organization Nagoya Medical Center
Division name	Department of Clinical Research Management, Clinical Research Center
Address	4-1-1 Sannomaru Nakaku Nagoya, Aichi, Japan
TEL	052-951-1111
Homepage URL
Email	bzm.nagoya@nnh.go.jp

Sponsor
Institute	St.Luke's International Hospital Daisuke Hasegawa National Hospital Organization Nagoya Medical Center Naoko Maeda Fukushima Medical University Hospital Atsushi Kikuta
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization
Nationality of Funding Organization	JAPAN

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	2014 Year 12 Month 17 Day

Progress
Recruitment status	No longer recruiting
Date of protocol fixation	2014 Year 11 Month 18 Day
Anticipated trial start date	2015 Year 01 Month 05 Day
Last follow-up date	2016 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete	2016 Year 04 Month 21 Day
Date analysis concluded	2016 Year 06 Month 30 Day

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

Management information
Registered date	2014 Year 12 Month 17 Day
Last modified on	2017 Year 07 Month 25 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018581