AML-SCT15

JRCT ID: jRCTs051180190

Registered date:26/03/2019

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: acute myeloid leukemia (AML)
• Date of first enrollment: 15/09/2017
• Target sample size: 66
• Study type: Interventional

Intervention(s)

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.
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.

Outcome(s)

• Primary Outcome: Probability of overall survival rate at three years after transplantation

Secondary Outcome

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

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: < 20age old
• Gender: Both

Include criteria

Inclusion criteria
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

Exclude 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

Related Information

• Primary Sponsor: YABE Hiromasa
• Secondary ID(s): UMIN000027821