UMIN-CTR Clinical Trial

Basic information
Public title	Phase II study of allogeneic hematopoietic cell transplantation for children with acute myeloid leukemia in first and second complete remission using fludarabine, cytarabine, melphalan and low-dose total body irradiation as a conditioning regimen (AML-SCT15).
Acronym	AML-SCT5
Scientific Title	Phase II study of allogeneic hematopoietic cell transplantation for children with acute myeloid leukemia in first and second complete remission using fludarabine, cytarabine, melphalan and low-dose total body irradiation as a conditioning regimen (AML-SCT15).
Scientific Title:Acronym	AML-SCT5
Region	Japan South America

Condition
Condition	acute myeloid leukemia (AML)
Classification by specialty	Hematology and clinical oncology Pediatrics
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To investigate safety and efficacy of reduced-intensity/toxicity stem cell transplantation using fludarabine, cytarabine, melphalan and low-dose total body irradiation as a substantial myeloablative conditioning regimen (FLAMEL) for children with high-risk AML in first complete remission or AML in second complete remission.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	Probability of overall survival rate at three years after transplantation
Key secondary outcomes	1) Efficacy Probability of event-free survival (EFS) rate, Cumulative incidence of relapse and non-relapse mortality (NRM) at 3 years after transplantation Probability of overall survival (OS) rate, EFS rate, Cumulative incidence of relapse and NRM at 10 years after transplantation Profile of cause of death at 3 and 10 years after transplantation Incidence of second transplantation and second malignant neoplasms 2) Short-term safety (up to 100 days after transplantation) Cumulative incidence of engraftment, secondary graft failure (2nd GF) and NRM at 100 days after transplantation Cumulative incidence and severity of acute and chronic graft-versus-host disease (GVHD), sinusoidal obstruction syndrome (SOS) and thrombotic microangiopathy (TMA) Incidence of and reason for donor lymphocyte infusion (DLI) Monitoring of chimerism at 1 and 3 months after FLAMEL regimen Profile of severe infectious disease after KIR ligand-mismatched cord blood transplantation Profile of conditioning regimen-related toxicities (Bearman criteria) up to 4 weeks after transplantation Profile of CTCAE (grade >=3) Cumulative days of fever (>=38C) 3) Long-term safety Cumulative incidence of engraftment, 2nd GF, SOS and TMA up to 1 year after transplantation Incidence of and reason for DLI up to one year after transplantation Cumulative incidence and severity of acute and chronic GVHD Monitoring of height (SD) and body weight (SD) after transplantation Monitoring of height (SD) of patients untreated with growth hormone Monitoring of TSH, free-T4, LH, FSH, testosterone, estradiol and anti-mullerian hormone Monitoring of Tanner stage and menstruation Incidence of growth disturbance, thyroid dysfunction and gonadal dysfunction at 3 and 10 years after transplantation Profile of CTCAE (grade >=3) up to 1 year after transplantation

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Active
Stratification	NO
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking
Concealment	No need to know

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	FLAMEL regimen: fludarabine (30 mg/m^2 x 1/day for 4 days), cytarabine (2 g/m^2 x 1/day for 4 days), melphalan (60 mg/m^2 x 1/day for 3 days) and low-dose total body irradiation (2 Gy x 1/day for one day) Graft: any of bone marrow, peripheral stem cell and cord blood. Graft-versus-host disease (GVHD) prophylaxis: in essentially tacrolimus or cyclosporine in combination with methotrexate.
Interventions/Control_2	For evaluation of secondary endo-points, patients received allogeneic transplantation using myeloablative conditioning regimens consisting of busulfan (> 8 mg/kg) or total body irradiation (>= 8 Gy, fractionated) are also enrolled to this study. Graft: any of bone marrow, peripheral stem cell and cord blood. Graft-versus-host disease (GVHD) prophylaxis: in essentially tacrolimus or cyclosporine in combination with methotrexate.
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	20 years-old >
Gender	Male and Female
Key inclusion criteria	Inclusion criteria 1) 1) AML (acute promyelocytic leukemia, AML which developed in patients with Down syndrome, secondary AML, AML which developed in patients with myelodysplastic syndrome, NK/myeloid leukemia and granulocytic leukemia are excluded) 2) Cases registered in the prospective study in JPLSG (JPLSG CHM-14) 3) Patients with high-risk AML in first complete remission or bone marrow-relapsed patients with AML in second complete remission 4) High-risk AML Any of the following a) Unfavorable chromosome abnormality including -7, del(5q)/-5, t(16;21)(p11;q22)/FUS-ERG, t(9;22)(q34;q11.2)/BCR-ABL1 or t(6;11)(q27;q23)/MLL-MLLT4(AF6), or unfavorable genetic abnormality including FLT3-ITD or NUP98-NSD1 b) Blast ratio >=5% in the bone marrow (M2/M3 marrow) after the first induction therapy c) Extramedullary lesions after the first induction therapy 5) Patients less than 18 years at the initial diagnosis in first remission, or patients less than 20 years at the relapse diagnosis in second remission 6) Written informed consent has been acquired from patients and/or persons with parental authority. 7) Cases in which a suitable donor is available and hematopoietic cell transplantation is considered to be mandatory 8) Patients whose performance status are 0 or 2 by ECOG criteria 9) Patients who satisfactory meet all of the following criteria about organ functions within 28 days prior to registration a) Patients without uncontrolled cardiac failure and ejection fraction of left ventricle >= 50% by UCG b) %VC >= 50% and FEV1.0% >= 50%, or SpO2 >= 95% by room air if pulmonary function tests are impossible c) AST/ALT < 5 x upper limit of normal range (CTCAE < grade 2) d) Patients without uncontrolled renal failure and sCr < 2 x upper limit of normal range
Key exclusion criteria	Exclusion criteria 1) Patients who have extramedullary lesions at registry 2) Patients who have prior radiation therapy 3) Patients who have prior hematopoietic cell transplantation 4) Patients who have poorly controlled infectious disease 5) Patients who have psychiatric disorder 6) Patients who have coinciding malignancies 7) Patients who have an episode of hypersensitivity reactions against drugs used in conditioning regimens and/or GVHD prophylaxis 8) Pregnant women or women who may be pregnant 9) Patients who are considered as inappropriate for this trial by attending physicians
Target sample size	66

Research contact person
Name of lead principal investigator	1st name Middle name Last name Hiromasa Yabe
Organization	Tokai University, School of Medicine
Division name	Department of Cell Transplantation and Regenerative Medicine
Zip code
Address	143, Shimokasuya, Isehara, Japan
TEL	0463-93-1121
Email	yabeh@is.icc.u-tokai.ac.jp

Public contact
Name of contact person	1st name Middle name Last name Hiroyuki Ishida / Katsutsugu Umeda
Organization	Kyoto City Hospital / Graduate School of Medicine, Kyoto University
Division name	Department of Pediatrics / Department of Pediatrics
Zip code
Address	1-2, Higashitakada-cho, Mibu, Nakagyou-ku, Kyoto / 54, Kawahara-cho, Shogoin, Sakyou-ku, Kyoto
TEL	075-311-5311.075-751-3290
Homepage URL	http://jplsg.jp/menu0_contents/index_menu_0.htm
Email	ishidah@koto.kpu-m.ac.jp

Sponsor
Institute	Japan Children's Cancer Group (JCCG)
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	Japan

Other related organizations
Co-sponsor
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	日本小児血液・がん研究組織参加施設

Other administrative information
Date of disclosure of the study information	2017 Year 07 Month 01 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	Enrolling by invitation
Date of protocol fixation	2017 Year 06 Month 16 Day
Date of IRB
Anticipated trial start date	2017 Year 07 Month 01 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2017 Year 06 Month 19 Day
Last modified on	2017 Year 12 Month 19 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031865

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name

Contact us.