UMIN-CTR Clinical Trial

Basic information
Public title	Allogeneic hematopoietic stem cell transplantation (HSCT) from HLA-haploidentical related donor using reduced dose of posttransplantation high-dose cyclophosphamide (PTCy) for poor prognosis or refractory hematological malignancies (OCU16-2)
Acronym	HLA-haploidentical HSCT with reduced dose of PTCy (OCU16-2)
Scientific Title	Allogeneic hematopoietic stem cell transplantation (HSCT) from HLA-haploidentical related donor using reduced dose of posttransplantation high-dose cyclophosphamide (PTCy) for poor prognosis or refractory hematological malignancies (OCU16-2)
Scientific Title:Acronym	HLA-haploidentical HSCT with reduced dose of PTCy (OCU16-2)
Region	Japan

Condition
Condition	Acute myeloid leukemia(AML) Acute lymphoblastic leukemia(ALL) Acute leukemias of ambiguous lineage Myelodysplastic syndrome(MDS) Chronic myeloid leukemia(CML) Adult T-cell leukemia/lymphoma(ATLL) Malignant lymphoma(ML)
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To assess the safety and efficacy of HLA-haploidentical allogeneic stem cell transplantation using reduced dose of posttransplantation cyclophosphamide from related donor for patients with poor-prognosis or refractory hematological malignancy who lack an HLA serological identical related donor.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Proportion of patients who survive with graft engraftment at 100 days fo1lowing 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	Historical
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), and melphalan (100 mg/ square meter per day for 1 day) are used as a conditioning regimen. Cyclophosphamide 50 mg/kg is given on day 3, 25 mg/kg on day 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 1,000 mg three times a 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	Among patients with refractory hematological disorders (indicated in the selection criteria) who are clinically adopted to allo-HSCT because they cannot expect to be cured or long-term survival by any other therapy, patients who do not have or not available HLA serological identical related donors and have HLA-haploidentical donors. 1) Age >= 15 and < 70 years old 2) ECOG PS 0 or 1 3) Normal function of major organs 4) Informed consent has been acquired 5)Indication (a) AML 1. Refractory to 1st induction therapy 2. Relapse after chemotherapy 3. Unfavorable chromosome abnormality including del(5q)/-5, -7/del(7q), abn 3q, 9q, 11q, 20q, 21q, 17q, t(6;9), t(9;22) or complex karyotype 4. Normal karyotype and FLT3-ITD mutation 5. Intermediate/poor group by JALSG score 6. AML with MRC 7. History of relapse after allo-HSCT 8. CR1 with standard risk or high risk (b) ALL 1. Refractory to 1st induction therapy 2. Relapse after chemotherapy 3. Any of 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 4. History of relapse after allo-HSCT (c) Acute leukemias of ambiguous lineage 1. Refractory to the first induction therapy 2. Relapse after chemotherapy 3. Unfavorable chromosome abnormality 4. History of relapse after allo-HSCT (d) MDS 1. RAEB-1 or 2 2. IPSS intermediate-2 or high 3. Transfusion dependent 4. History of relapse after allo-HSCT (e) CML 1. AP or BC: refractory to multiple TKIs 2. CP beyond 1st CP or AP 3. History of relapse after allo-HSCT (f) ATLL, ML 1. ATLL Acute or lymphoma type in the PR or better 2. ML Malignant lymphoma which is classified in the 2008 WHO classification which relapse after auto-HSCT, or which have no indication for auto-HSCT due to no sensitivity to chemotherapy or poorly controlled disease with conventional chemotherapy
Key exclusion criteria	1) Major organ dysfunction a) Total bilirubin: >= 2.0 mg/dl b) Serum creatinine: >= 2.0 mg/dl c) Left ventricular 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 woman or woman of childbearing potential 8) Patients with a severe mental disorder 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) A history of administration of mogamulizumab 12) 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	33

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

Public contact
Name of contact person	1st name Hirohisa Middle name Last name Nakamae
Organization	Osaka City University, Graduate School of Medicine
Division name	Hematology
Zip code	545-8585
Address	1-4-3, Asahi-machi, Abeno-ku, Osaka, Japan
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)

IRB Contact (For public release)
Organization	Osaka City University Hospital Certified Review Board
Address	1-2-7, Asahi-machi, Abeno-ku, Osaka, Japan, 545-0051
Tel	06-6645-3456
Email	irb@med.osaka-cu.ac.jp

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	2017 Year 02 Month 08 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
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

Progress
Recruitment status	No longer recruiting
Date of protocol fixation	2017 Year 02 Month 06 Day
Date of IRB	2017 Year 02 Month 06 Day
Anticipated trial start date	2017 Year 02 Month 09 Day
Last follow-up date	2021 Year 04 Month 30 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2017 Year 02 Month 07 Day
Last modified on	2019 Year 12 Month 11 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029711