UMIN-CTR Clinical Trial

Basic information
Public title	A Pharmacokinetics (PK)/Phase I study of intravenous (i.v.) administration of mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (allo-SCT)
Acronym	A PK/Phase I study of i.v. MMF for GVHD prophylaxis
Scientific Title	A Pharmacokinetics (PK)/Phase I study of intravenous (i.v.) administration of mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (allo-SCT)
Scientific Title:Acronym	A PK/Phase I study of i.v. MMF for GVHD prophylaxis
Region	Japan

Condition
Condition	Refractory hematologic disorders, including 1. Acute myelogenous leukemia 2. Acute lymphoblastic leukemia 3. Myelodysplastic syndrome 4. Chronic myelogenous leukemia 5. Malignant lymphoma 6. Aplastic anemia
Classification by specialty	Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	This PK/Phase I study is conducted to establish i.v. MMF dosing for GVHD prophyraxis as a substitute for p.o. MMF at the inability to oral intake after allo-SCT.
Basic objectives2	Pharmacokinetics
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	1. PK analysis of i.v. MMF, and comparison of PK parameters between i.v. and p.o. MMF 2. Grade of treatment-related toxicity by using i.v. MMF
Key secondary outcomes	1. Time to hematopoietic recovery 2. The cumulative incidence and severity of acute GVHD until day 100 3. Overall survival and progression-free survival at day 100 and 1-year after allo-SCT 4. Drug interaction studies with MMF

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	For GVHD prophylaxis, MMF is administered 4-6 h after allo-SCT at a dose of 1000 mg i.v. (diluted to a concentration of 6 mg/ml using 5% Dextrose, over 2 h) thrice daily (or twice daily in the case of cord blood transplantation) from day 0 to day 10 (for up to 14 days). Thereafter, patients are changed to p.o. MMF at the same dose and interval. After day 31, the dose tapers depending on individual risk factors for GVHD. Blood samples (2 ml) for PK analysis are collected in EDTA tubes at 0, 0.5, 1, 2, 4, 8, and 12 h after the morning dose on days 2 and 9 during i.v. MMF administration and at 0, 1, 2, 4, 8, and 12 h on day 16 during p.o. MMF administration. Total mycophenolic acid (MPA) levels are quantified by reverse-phase HPLC. After quantification, non-compartmental analyses of total MPA concentration time data are conducted to estimate the AUC.
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	69 years-old >=
Gender	Male and Female
Key inclusion criteria	1. Age between 15 and 69 years 2. ECOG performance status 0 or 1 3. Written informed consent for participation
Key exclusion criteria	1. Contraindication of MMF administration 2. SpO2 of less than 93% without oxygen inhalation 3. Serum creatinin of greater than 2.0mg/dl 4. Liver function with serum total bilirubin of greater than 2.0mg/dl, or AST of greater than 4.0 x ULN 5. Left ventricular ejection fraction of less than 50% 6. Past history of cardiac event, or significant cardiac disease 7. Uncontrolled diabetus mellitus 8. Another active neoplastic disease 9. Uncontrolled active infections 10. Serologically positive for HIV antibody and/or HBs antigen 11. Pregnant, or during breast feeding 12. Uncontrolled psychiatric disease 13. Allergic history to drugs used in the conditioning regimens or GVHD prophylaxis regimens 14. Patients suggested as ineligible by their attending physician
Target sample size	10

Research contact person
Last name of lead principal investigator	1st name Middle name Last name Hironobu Minami
Organization	Kobe University Graduate School of Medicine
Division name	Medical Oncology/Hematology, Department of Medicine
Zip code
Address	7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo
TEL	078-382-5820
Email	hminami@med.kobe-u.ac.jp

Public contact
1st name of contact person	1st name Middle name Last name Atsuo Okamura
Organization	Kobe University Hospital
Division name	Medical Oncology/Hematology
Zip code
Address	7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo
TEL	078-382-5820
Homepage URL
Email	atsuo@med.kobe-u.ac.jp

Sponsor
Institute	Kobe University Graduate School of Medicine
Institute
Department

Funding Source
Organization	None
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor	School of Pharmacy and Pharmaceutical Science, Mukogawa Women's University
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

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	神戸大学医学部附属病院（兵庫県）

Other administrative information
Date of disclosure of the study information	2010 Year 11 Month 01 Day

Related information
URL releasing protocol
Publication of results	Published

Result
URL related to results and publications	https://www.ncbi.nlm.nih.gov/pubmed/295117
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	Completed
Date of protocol fixation	2010 Year 09 Month 02 Day
Date of IRB
Anticipated trial start date	2010 Year 11 Month 01 Day
Last follow-up date	2016 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2010 Year 09 Month 24 Day
Last modified on	2018 Year 10 Month 01 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005113

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name

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