UMIN-CTR Clinical Trial

Basic information
Public title	A Phase I study of Inotuzumab Ozogamicin as a single agent for pediatric patients in Japan with relapsed/refractory CD22-positive Acute Lymphoblastic Leukemia
Acronym	A Phase I study of Inotuzumab Ozogamicin as a single agent for pediatric patients in Japan with relapsed/refractory CD22-positive Acute Lymphoblastic Leukemia
Scientific Title	A Phase I study of Inotuzumab Ozogamicin as a single agent for pediatric patients in Japan with relapsed/refractory CD22-positive Acute Lymphoblastic Leukemia
Scientific Title:Acronym	A Phase I study of Inotuzumab Ozogamicin as a single agent for pediatric patients in Japan with relapsed/refractory CD22-positive Acute Lymphoblastic Leukemia
Region	Japan

Condition
Condition	Relapsed or refractory CD22-positive ALL Relapsed or refractory CD22-positive lymphoblastic lymphoma and bone marrow involvement
Classification by specialty	Hematology and clinical oncology Pediatrics
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To assess the safety and tolerability of inotuzumab ozogamicin in pediatric subjects in Japan with relapsed/refractory CD22 positive ALL/Lymphoblastic Lymphoma (referred to as ALL) in order to select the recommended clinical dose.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Others
Trial characteristics_2
Developmental phase	Phase I

Assessment
Primary outcomes	Incidence of first cycle dose limiting toxicities (DLTs) of inotuzumab ozogamicin
Key secondary outcomes	1) PK profile of inotuzumab ozogamicin 2) Safety profile, including VOD/SOS 3) Complete remission rate (CR/CRi ) 4) Minimal residual disease (MRD) status in patients achieving a CR/CRi 5) Overall survival (OS)

Base
Study type	Interventional

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

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	For the dose level 1 (starting dose), pediatric patients with ALL will be treated with 1.8 mg/m2 inotuzumab ozogamicin per cycle with a fractionated dose regimen. Patients will receive 0.8 mg/m2 on Day 1, followed by 0.5 mg/m2 on Day 8 and Day 15. 1 cycle is 21 days for Cycle 1 and 28 days for Cycle 2 and after. For Cycle 2 and after, the dose of inotuzumab ozogamicin on Day 1 will be reduced to 0.5 mg/m2 (for a total cycle dose of 1.5 mg/m2) in patients who achieve a CR or CRi. If patients have not achieved CR or CRi after the first cycle, the same dose as Cycle 1 will be used (for a total cycle dose of 1.8 mg/m2). The dose levels -1 and -2 will be used according to the same schedule as that for the dose level 1. For patients who may not undergo HSCT, it is recommended that treatment with inotuzumab ozogamicin be limited to 6 cycles, but the treatment will be discontinued if CR/CRi not achieved within 3 cycles. For patients who may undergo HSCT, since the risk of VOD/SOS may increase in accordance with the increasing number of cycles, the treatment must be up to a minimum number of cycles at which patients gain benefit. The treatment should be up to 3 cycles unless more treatment is considered to be necessary.
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	17 years-old >=
Gender	Male and Female
Key inclusion criteria	1. Relapsed or refractory CD22-positive ALL (>=5% marrow blasts, assessed by morphology), or relapsed or refractory CD22-positive lymphoblastic lymphoma and bone marrow involvement >=5% lymphoblasts by morphologic assessment. 2. Ph+ ALL patients must have failed treatment with at least 1 second or third generation tyrosine kinase inhibitor and standard multi-agent induction chemotherapy; 3. Patients with late relapse should be deemed poor candidates for reinduction with initial therapy; 4. Patients from 1 to 17 years old at the timing of informed consent. 5. Karnofsky performance status 60% to 100% for patients >=17 years of age and Lansky performance status 60% to 100% for patients <=16 years of age 6. Adequate liver function, including total serum bilirubin <=1.5 x ULN unless the patient has documented Gilbert syndrome, and aspartate and alanine aminotransferase (AST and ALT) <=2.5 x ULN. If organ function abnormalities are considered due to tumor, total serum bilirubin must be <=2 x ULN and AST/ALT <=2.5 x ULN. Pediatric reference ranges will be used. 7. Serum creatinine <=1.5 x upper limit of normal (ULN) (pediatric reference ranges will be used) or estimated creatininee clearance of >=40 mL/min by standard calculation method of site. 8. Pregnant, lactating, childbearing potential female or childbearing potential male must agree to use a highly effective method of contraception throughout the study and for a minimum of 90 days after the last dose of treatment. 9. Evidence that an informed consent document personally signed and dated by the patient or the legal representative such as parents indicates that the patient has been informed of all pertinent aspects of the study before any study specific activity is performed; 10. Patients who are able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 11. Asian patient.
Key exclusion criteria	1. Isolated extramedullary relapse (testicular or CNS) 2. Burkitt's or mixed phenotype acute leukemia (WHO 2008 criteria) 3. Active central nervous system leukemia. Prophylactic intrathecal medication is not excluded. 4. Having undergone prior chemotherapy at enrollment excluding therapy to reduce the circulating lymphoblast count or palliation: steroids, hydroxycarbamide, or vincristine 5. Prior administration of monoclonal antibodies within 4 weeks of enrollment 6. Prior rituximab treatment at enrollment 7. Prior allogeneic HSCT or other anti-CD22 immunotherapy <=4 months before enrollment 8. Having completed immunosuppression therapy in GvHD prior to enrollment. With >= Grade 2 acute GvHD, or extensive chronic GvHD at enrollment 9. Systemic vasculitides, or primary or secondary immunodeficiency 10. Active HbsAg B or HCV C infection or seropositivity for HIV 11. Major surgery within <=4 weeks before enrollment 12. Unstable or severe uncontrolled medical condition 13. Concurrent active malignancy excluding non-melanoma skin cancer that has been definitely treated with radiation or surgery, calculated cervical high grade squamous intraepithelial lesion (CIN2, CIN3), or localized prostate cancer. Those with previous malignancies in disease free for >=2 years 14. <45% cardiac function (left ventricular ejection fraction), or class >=3 (Modified Ross Heart Failure Classification) 15. Active heart disease 16. Myocardial infarction <=6 months before enrollment 17. History of chronic liver disease 18. History of hepatic veno-occlusive disease or sinusoidal obstruction syndrome 19. Live vaccine administration <=6 weeks before enrollment 20. Evidence of serious active infection 21. History of severe allergic or anaphylactic reaction to any humanized monoclonal antibodies 22. Participation in other studies 23. History of Inotuzumab ozogamicin administration
Target sample size	18

Research contact person
Name of lead principal investigator	1st name Keizo Middle name Last name Horibe
Organization	National Hospital Organization Nagoya Medical Center
Division name	Clinical Research Center
Zip code	460-0001
Address	4-1-1 Sannomaru, Naka-ku, Nagoya, Aichi, Japan
TEL	052-951-1111
Email	keizo.horibe@nnh.go.jp

Public contact
Name of contact person	1st name Yutaka Middle name Last name Ito
Organization	National Hospital Organization Nagoya Medical Center
Division name	Department of Clinical Research Planning and Management, Clinical Research Center
Zip code	460-0001
Address	4-1-1 Sannomaru, Naka-ku, Nagoya, Aichi, Japan
TEL	052-951-1111
Homepage URL
Email	study.office@nnh.go.jp

Sponsor
Institute	National Cancer Center Hospital Nagoya Medical Center Osaka City General Hospital Kyushu Cancer Center Hyogo Prefectural Kobe Children's Hospital
Institute
Department

Funding Source
Organization	Pfizer Inc.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

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

IRB Contact (For public release)
Organization	National Hospital Organization Nagoya Medical Center Institutional Review Board
Address	4-1-1 Sannomaru, Naka-ku, Nagoya, Aichi, Japan
Tel	052-951-1111
Email	311-chiken@mail.hosp.go.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	国立がん研究センター中央病院（東京都） 名古屋医療センター（愛知県） 大阪市立総合医療センター（大阪府） 九州がんセンター（福岡県） 兵庫県立こども病院（兵庫県）

Other administrative information
Date of disclosure of the study information	2018 Year 07 Month 20 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	2018 Year 06 Month 20 Day
Date of IRB	2018 Year 07 Month 20 Day
Anticipated trial start date	2018 Year 09 Month 01 Day
Last follow-up date	2021 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2018 Year 07 Month 10 Day
Last modified on	2021 Year 07 Month 12 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037897