UMIN-CTR Clinical Trial

Public title

A phase II study of allogeneic stem cell transplantation for elderly patients with hematologic malignancies using fludarabine and intravenous busulfan.

Acronym

JSCT-FB09

Scientific Title

A phase II study of allogeneic stem cell transplantation for elderly patients with hematologic malignancies using fludarabine and intravenous busulfan.

Scientific Title:Acronym

JSCT-FB09

Region

Japan

Condition

AML,MDS

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To investigate safety and efficacy of allogeneic stem cell transplantation using 180mg/m2 of fludarabine and 12.8mg/kg of intravenous busulfan for elderly patients aged 55-70 with AML or MDS. As an accompanying study, blood concentration of intravenous busulfan will be assessed to investigate pharmacokinetics of this drug in the elderly in comparison with that of younger patients, supported by a Research grant from the Japanese Ministry of Health, Labor and Welfare (PI: Dr. S. Mori at National Cancer Center Hospital, Japan).

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Phase II

Primary outcomes

To determine overall survival with neutrophil engraftment at 60 days after transplantation

Key secondary outcomes

1.Acomplishment rate of conditioning regimen
2.Incidence of grade 3 or higher adverse events up to 30 days after transplantation
3.Probability of achieving complete donor chimerism in 100 days after transplantation
4.Incidence of non-relapse mortality in 100 days after transplantation
5.Incidence of infections in 1 year after transplantation
6.Probabilities of disease-free survivals at 1 and 2 years after transplantation
7.Cumulative incidence of relapse at 1 and 2 years after transplantation
8.Probabilities of overall survival at 1 and 2 years after transplantation
9.Incidence and severity of acute and chronic GVHD in 1 and 2 years after transplantation
10.Sub-group analysis of above mentioned secondary outcomes according to stem cell sources

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Conditioning regimen:
HLA matched related bone marrow (BM) or peripheral blood stem cell (PBSC) donor
Flu 180mg/m2 + ivBu 12.8mg/kg
HLA mismatched related BM or PBSC donor and unrelated BM donor
Flu 180mg/m2 + ivBu 12.8mg/kg +- TBI 2Gy
cord blood (CB) donor
Flu 180mg/m2 + ivBu 12.8mg/kg + TBI 2Gy X 2

GVHD prophylaxis:
HLA matched related BM or PBSC donor
cyclosporine A(CsA) + short-term
methotrexate(MTX)(day 1: 10mg/m2, day 3, 6: 7mg/ m2)
HLA mismatched related BM or PBSC donor and unrelated BM donor
tacrolimus + short-term MTX(day 1: 10mg/m2, day 3, 6, 11: 7mg/m2, administation of MTX on day11 may be omitted by each physician's decision.)

CB donor
tacrolimus + oral mycophenolate mofetil (MMF)(30mg/kg/day in two divided doses, from day 0 to 30, and subsequently tapered and discontinued within 2 weeks, privided that there is no active GVHD requiring treatment)

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

Age-lower limit

55

years-old

<=

Age-upper limit

70

years-old

>=

Gender

Male and Female

Key inclusion criteria

1.Patients diagnosed as AML or MDS who meet the following conditions,
(a)Patients with AML(except M3)who are in advanced stage beyond first complete remission, are in high risk disease category according to SWOG/ECOG criteria, received more than one course of chemotherapy to achieve complete remission, AML/MLD in first remission, or AML with prior history of myelodysplastic syndrome
(B)Patients with MDS who are in poor prognosis group with high or very high score according to WHO classification-based prognostic scoring system, or required platelet transfusions of at least 10 units/week or red cell transfusions of at least 2 units/month.
2.Age:55-70
3.Those who have available donors(HLA-identical or 1 antigen-mismatched related BM/PBSC, HLA-matched or 1 DR antigen-mismatched unrelated BM, and HLA matched or less than 3 antigen-mismatched CB with more than 2 X 10^7/kg nucleated cells.
4.ECOG PS:0-2
5.Those who have no severe organ dysfunction (T. Bil<2.0mg/ml, AST<=3 X upper limit of normal,ALT<=3 X upper limit of normal, Cr<2.0mg/dl, EF>50%, SpO2>95%)
6.Those who give written informed consent following sufficient explanation.
7.Those who are evaluated to be able to survive more than 3 months.

Key exclusion criteria

1.Those who are positive for anti-HIV antibody
2.Those who have history of gemtuzumab ozogamicin (MylotargTM) use within 4 months
3.Those who have coinciding active malignancies
4.Those who have uncontrolled psychiatric disorder
5.Those who have active infection
6.Those who have prior hematopoietic stem cell transplantation
7.Those who have history of chemotherapy within 30 days before transplant (except hydroxycarbamide or cytarabine therapy for blast control)
8.Those who have hypersensitivity to drugs included in this protocol therapy
9.Those who are considered as inappropriate to register by attending physicians.

Target sample size

36

Name of lead principal investigator

1st name
Middle name
Last name	Naoya Uchida

Organization

Toranomon Hospital, Tokyo, Japan

Division name

Department of Hematology

Zip code

Address

2-2-2,Toranomonn,Minato-ku,Tokyo,Japan

TEL

03-3588-1111

Email

Name of contact person

1st name
Middle name
Last name

Organization

JSCT

Division name

FB09 datacenter

Zip code

Address

2-10-7,Yaesu,Chuou-ku,Tokyo,Japan

TEL

03-6225-2025

Homepage URL

http://jsct.jp/

Email

jsct-office@umin.ac.jp

Institute

Japan Study Group for Cell Therapy and Transplantation

Institute

Department

Personal name

Organization

Resarch Foundation for Community Medicine

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

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

Date of disclosure of the study information

2009

Year

09

Month

01

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results: 142 elderly patients (88 men and 54 women; median age, 61 years; range, 55-70 years) were participated, 103 AML and 39 MDS. 21 received related bone marrow (BM) or peripheral blood (PB), 50 did unrelated BM, and 71 did cord blood (CB). 105 (74%) experienced grade III or greater toxicities including 4 SOS. Neutrophil engraftment was achieved in 70 out of 71 related BM/PB or unrelated BM recipients, and 61 of 71 UCB recipients. Cumulative incidences of relapse and non-relapse mortality after 2 years were 24 % and 24.1%, respectively. Overall and event-free survivals at 2 years were 53.3% and 47.4 %, respectively. 2-year OS was 61.5% in related BM/PB, 67.8% in UBM, and 40.8% in CB recipients, showing inferior OS in CB recipients to the other donor types (P<0.05). However, for those in good performance status (ECOG 0) and had low blast count in BM (<5%), the differences became not significant (2-year OS were 77.3% in related BM/PB, 68.4% in UBM, and 65.0% in CB recipients).
Conclusion: The myeloablative dose of ivBu was well tolerated without increased toxicity-related mortality. The differences between CB and the others could likely be due to relatively poor conditions of CB recipients. This trial was registered as #UMIN000002426, #UMIN000004213, and #UMIN000004211.

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

Main results already published

Date of protocol fixation

2009

Year

09

Month

01

Day

Date of IRB

Anticipated trial start date

2009

Year

09

Month

01

Day

Last follow-up date

2013

Year

09

Month

01

Day

Date of closure to data entry

Date trial data considered complete

2013

Year

09

Month

02

Day

Date analysis concluded

2013

Year

10

Month

02

Day

Other related information

Registered date

2009

Year

09

Month

01

Day

Last modified on

2018

Year

03

Month

21

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002971