UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	HLA-haploidentical allogeneic stem cell transplantation for refractory hematopoietic malignancies (OCU13-3)
Title of the study (Brief title)	HLA-haploidentical allogeneic stem cell transplantation for refractory hematopoietic malignancies (OCU13-3)
Region	Japan

Condition
Condition	Acute myeloid leukemia(AML) Acute lymphoblastic leukemia (ALL) Chronic myeloid leukemia (CML) Myelodysplastic syndrome (MDS)
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To assess the safety and efficacy of HLA-haploidentical allogeneic stem cell transplantation from related donor for patients with poor-prognosis or refractory leukemia or myelodysplastic syndrome (MDS) who lack an HLA serological identical related donor.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	Proportion of patients who survive with graft engraftment at 100 days following transplantation
Key secondary outcomes

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	Fludarabine (15 mg/square meter of body surface area twice a day for 2 days and 30 mg/square meter once a day for 4 days), cytarabine (2 g/square meter twice a day for 2 days), Melphalan (100mg/ square meter per day for 1 day) is used as a conditioning regimen. Cyclophosphamide (25 mg/kg) is given on day 3, 4 after the graft infusion. The donor source is peripheral blood stem cell. Continuous intravenous tacrolimus (0.03 mg/kg/day) and oral mycophenolate mofetil 3,000mg/day are initiated from day 5 after transplantation.
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	15 years-old <=
Age-upper limit	70 years-old >
Gender	Male and Female
Key inclusion criteria	1) Patients with poor-prognosis or refractory leukemia or MDS who lack an HLA serological identical related donor. 2) Patients who have an HLA -haploidentical donor of family member or relative 3) Age >=15 and < 70 years old 4) ECOG PS 0 or 1 5) Normal function of major organs 6) Informed consent has been acquired. 7) Patients who are in need of a prompt allogeneic transplant a) De novo AML: refractory to first induction therapy or relapse after chemotherapy b) ALL: refractory to first induction therapy or relapse after chemotherapy c) CML in AP or BC: refractory to TKIs including imatinib, dasatinib and nilotinib d) Patients with AML, ALL, CML or MDS who have relapsed after allogeneic transplant 8) Patients who have an indication for allogeneic transplantation due to an unfavorable prognosis but lack a suitable related donor a) Patients with de novo AML in the CR with an unfavorable chromosome abnormality including del(5q)/-5,- 7/del(7q), abn 3q, 9q, 11q, 20q, 21q, 17q, t(6;9), t(9;22) or a complex karyotype b) Patients with de novo AML in the CR with normal karyotype and FLT3-ITD mutation c) Patients with AML with intermediate/poor group by JALSG score d) Patients with ALL in 1CR who have the following poor prognostic factors i) t(9;22) or t(4;11) ii) >=35 years of age at diagnosis iii) WBC count of more than 30,000/uL for B- ALL, or more than 100,000/uL for T-ALL at diagnosis e) AML, ALL in the CR state except for 1CR f) CML in the CR state except for 1CR g) MDS with RAEB-1, 2, AML with MRC h) Patients with AML, ALL, or CML in CP who have relapsed after allogeneic transplant
Key exclusion criteria	1) Major organ dysfunction a) Total bilirubin:>= 2.0mg/dl b) Serum creatinine: >= 2.0mg/dl c) Ejection fraction: < 50 % d) Pulmonary function test: %VC <40%, FEV1.0% <50% or SaO2 <90% on room air e) AST or ALT >= 3 x UNL 2) Uncontrolled active infection 3) Uncontrolled CNS invasion 4) Poorly controlled insulin-treated diabetes mellitus 5) Poorly controlled hypertension 6) Patients with a severe complication including heart failure, coronary failure, acute myocardial infarction within the last three months, liver cirrhosis and interstitial pneumonia 7) Pregnant, lactating or possible fertile women who may become pregnant 8) Patients with a severe mental who are likely to be unable to participate in the study 9) A history of hypersensitivity or allergy to any drugs in the conditioning regimen of this transplant 10) HIV antibody positivity 11) The physician in charge determines that there is no indication to perform this intervention. (Note: HBs antigen positivity and HCV antibody positivity is not exclusion criterion.)
Target sample size	35

Research contact person
Name of lead principal investigator	Hirohisa Nakamae
Organization	Graduate School of Medicine, Osaka City University
Division name	Hematology
Address	1-4-3, Asahi-machi, Abeno-ku, Osaka, Japan. 545-8585
TEL	06-6645-3881
Email	hirohisa@msic.med.osaka-cu.ac.jp

Public contact
Name of contact person	Hirohisa Nakamae
Organization	Graduate School of Medicine, Osaka City University
Division name	Hematology
Address	1-4-3, Asahi-machi, Abeno-ku, Osaka, Japan. 545-8585
TEL	06-6645-3881
Homepage URL
Email	hirohisa@msic.med.osaka-cu.ac.jp

Sponsor
Institute	Osaka City University
Institute
Department

Funding Source
Organization	Osaka City University
Organization
Division
Category of Funding Organization	Self funding
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	2013 Year 07 Month 26 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2013 Year 07 Month 04 Day
Anticipated trial start date	2013 Year 08 Month 01 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2013 Year 07 Month 26 Day
Last modified on	2018 Year 12 Month 05 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013231