UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Allogeneic hematopoietic stem cell transplantation from HLA6/8-4/8 matched related donor for poor prognostic or refractory hematologic malignancy and solid tumor - Ibaraki Children's Hospital phase II study
Title of the study (Brief title)	ICH-HAPLO-16
Region	Japan

Condition
Condition	Acute leukemia, malignant lymphoma, and solid tumor
Classification by specialty	Hematology and clinical oncology Pediatrics Child
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To evaluate the safety and efficacy of haploidentical family member, reduced toxicity hematopoietic stem cell transplantation against refractory hematologic malignancy and solid tumor in an attempt to reduce the late adverse effect and improve the prognosis
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	Disease free survival rate at day 60 after transplantation
Key secondary outcomes	Engraftment rate at 30 days after transplantation Achievement rate of complete chimerism at 30 days after transplantation Cumulative incidence of acute GVHD over a 1-year period Cumulative incidence of grade 2 to 4 acute GVHD over a 1-year period Cumulative incidence of grade 3 to 4 acute GVHD over a 1-year period Cumulative incidence of hemorrhagic cystitis over a 1-year period Cumulative incidence of thrombotic microangiopathy over a 1-year period Cumulative incidence of hepatic sinusoidal obstruction syndrome over a 1-year period Cumulative incidence of idiopathic pneumonia syndrome over a 1-year period Cumulative therapy-related mortality over a 2-year period Cumulative incidence of chronic GVHD over a 3-year period Cumulative incidence of severe chronic GVHD over a 3-year period Relapse free survival rate at 1 year after transplantation Overall survival rate at 1 year after transplantation Relapse free survival rate at 3 years after transplantation Overall survival rate at 3 years after transplantation Cumulative incidence of relapse over a 1-year period Cumulative incidence of relapse over a 3-year period

Base
Study type	Interventional

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

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Maneuver
Interventions/Control_1	Patients receive peripheral blood stem cell transplantation or bone marrow transplantation from HLA-4/8 to 6/8 matched family member after preconditioning with 180mg/m^2 of fludarabine, 140-210mg/m^2 of melphalan, and 2.5-5.0mg/kg of rabbit anti-thymocyte globulin, added with 4-6Gy of total body irradiation or 6.4-9.6mg/kg of busulfan depending on the disease condition. The patient was followed with intensive GVHD prophylaxis composed of methotrexate, tacrolimus, and methylprednisolone. The graft was analyzed by flowcytometry. The patients undergo physical examination, serial peripheral blood investigation, bone marrow analysis, and imaging study over chimerism, engraftment, immunological recovery, disease condition, or side effect.
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	0 years-old <=
Age-upper limit	20 years-old >
Gender	Male and Female
Key inclusion criteria	(1)Histologically or cytologically diagnosed acute leukemia, or malignant lymphoma, or solid tumor (2)Age less than 20 years at diagnosis (3)Confirmed Eligible clinical entity (3-1)High Risk acute leukemia or malignant lymphoma (a)Primary induction failure at transplantation (b)In the first complete remission obtained after more than three courses of induction (c)In the first complete remission with detectable minimum residual disease (d)In the first complete remission with unfavorable cytogenetic or molecular features (e)Very early relapse within three years after diagnosis, the second complete remission but poor response or minimum residual disease against re-induction chemotherapy after relapse, the third or more advanced complete remission or not in remission after relapse (3-2)High risk solid tumor (a)MYCN-amplified, 1p-lost, or 11q-lost neuroblastoma (b)Not in remission (3-3)No HLA-match donor in family and no appropriate donor in unrelated donor bank or cord blood bank (3-4)Recurrent acute leukemia or malignant lymphoma after hematopoietic stem cell transplantation (3-5)Recurrent solid tumor (4)ECOG performance status score 0-1, if deterioration due to active disease, score 2 eligible (5)Appropriate organ function fulfilling following condition a)Serum concentration of total bilirubin, less than upper limit of normal range for age b)Serum concentration of creatinine, less than upper limit of normal range for age c)Serum concentration of cystatin C, less than 1.00 mg/L d)Pulse-oximetry saturation more than 97 percent awake and at rest breathing room air e)%Vital capacity, more than 70% by pulmonary function test (if patient more than 6 years old) f)Forced expiratory volume in 1 second%, more than 70% (if patient more than 6 years old) g)Plasma BNP, less than 40 pg/mL h)%Fractional shortening, more than 27% (6)All patients and/or their parents or legal guardians must sign a written informed consent
Key exclusion criteria	(1)Germ line chromosomal abnormality other than trisomy 21 (2)Concurrent or prior malignant disease other than the original disease in interest or prior organ transplantation other than hematopoietic cell transplantation (3)Congenital or acquired immunodeficiency (4)Uncontrolled fungal, bacterial, or viral infection (including tuberculosis of HIV) (5)Pregnant, lactating, or highly suspected to be pregnant (6)Corrected QT interval by Fridericia, more than 0.45 second (7)Active hemorrhage in central nervous system, fulfilling grade more than 3 on CTCAE version 4.0 (8)Consciousness disturbance, score less than 14 on Glasgow Coma Scale (9)Obesity, by more than 30% of average weight for age. (10)Considered to be unsuitable for entry for the study
Target sample size	30

Research contact person
Name of lead principal investigator	Keisuke Kato, M.D.
Organization	Ibaraki Children's Hospital
Division name	Division of Pediatric Hematology and Oncology, Specialty Care Service, Pediatrics
Address	Futaba-dai 3-3-1, Mito, Japan
TEL	029-254-1151
Email	keikato-ind@umin.ac.jp

Public contact
Name of contact person	Keisuke Kato, M.D.
Organization	Ibaraki Children's Hospital
Division name	Division of Pediatric Hematology and Oncology, Specialty Care Service, Pediatrics
Address	Futaba-dai 3-3-1, Mito, Japan
TEL	029-254-1151
Homepage URL
Email	keikato-ind@umin.ac.jp

Sponsor
Institute	Ibaraki Children's Hospital
Institute
Department

Funding Source
Organization	Ibaraki Children's Hospital
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

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	茨城県立こども病院小児血液腫瘍科

Other administrative information
Date of disclosure of the study information	2017 Year 04 Month 17 Day

Progress
Recruitment status	Enrolling by invitation
Date of protocol fixation	2016 Year 10 Month 18 Day
Anticipated trial start date	2016 Year 10 Month 18 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

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

Management information
Registered date	2017 Year 04 Month 16 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=R000030105