UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A phase II study of allogeneic stem cell transplantation for elderly patients with hematologic malignancies using fludarabine and intravenous busulfan.
Title of the study (Brief title)	JSCT-FB09
Region	Japan

Condition
Condition	AML,MDS
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
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

Assessment
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

Base
Study type	Interventional

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

Intervention
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

Eligibility
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

Research contact person
Name of lead principal investigator	Naoya Uchida
Organization	Toranomon Hospital, Tokyo, Japan
Division name	Department of Hematology
Address	2-2-2,Toranomonn,Minato-ku,Tokyo,Japan
TEL	03-3588-1111
Email

Public contact
Name of contact person
Organization	JSCT
Division name	FB09 datacenter
Address	2-10-7,Yaesu,Chuou-ku,Tokyo,Japan
TEL	03-6225-2025
Homepage URL	http://jsct.jp/
Email	jsct-office@umin.ac.jp

Sponsor
Institute	Japan Study Group for Cell Therapy and Transplantation
Institute
Department

Funding Source
Organization	Resarch Foundation for Community Medicine
Organization
Division
Category of Funding Organization	Non profit foundation
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

Other administrative information
Date of disclosure of the study information	2009 Year 09 Month 01 Day

Progress
Recruitment status	Main results already published
Date of protocol fixation	2009 Year 09 Month 01 Day
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

Related information
URL releasing protocol
Publication of results	Published
URL releasing results
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.
Other related information

Management information
Registered date	2009 Year 09 Month 01 Day
Last modified on	2018 Year 03 Month 21 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000002971