UMIN-CTR Clinical Trial

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

acute myeloid leukemia (AML)

Classification by specialty

Hematology and clinical oncology

Pediatrics

Classification by malignancy

Malignancy

Genomic information

YES

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

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

Study type

Interventional

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

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

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

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

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

Institute

Japan Children's Cancer Group (JCCG)

Institute

Department

Personal name

Organization

Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

日本小児血液・がん研究組織参加施設

Date of disclosure of the study information

2017

Year

07

Month

01

Day

URL releasing protocol

Publication of results

Unpublished

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

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 related information

Registered date

2017

Year

06

Month

19

Day

Last modified on

2017

Year

12

Month

19

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031865