UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Phase 1/2 study of adoptive cell therapy using cultured tumor infiltrating lymphocytes with lympho-depleting non-myeloablative preconditioning for patients with advanced melanoma
Title of the study (Brief title)	MM-TIL-P1/2
Region	Japan

Condition
Condition	Advanced malignant melanoma
Classification by specialty	Dermatology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	Evaluate the safety and efficacy of young tumor infiltrating lymphocytes ( young TIL) -adoptive cell therapy (ACT) with low dose IL-2 following a non-myeloablative chemotherapy preparative regimen in unresectable/metastatic malignant melanoma
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Phase I,II

Assessment
Primary outcomes	Overall response rate, Safety
Key secondary outcomes	Duration response, Duration of stable disease, Progression-free survival, Overall survival

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 Maneuver
Interventions/Control_1	Metastasectomy (day-35) Non-myeloablative lymphocyte depleting preparative regimen (day-7~-3) Transfer cultured tumor infiltrating lymphocytes (day0) Low-dose interleukin-2(72,000IU/kg, q8hr) (day0~2, maximum 5 times)
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	20 years-old <=
Age-upper limit	65 years-old >=
Gender	Male and Female
Key inclusion criteria	1) Have histopathologically confirmed malignant melanoma. 2) Have unresectable stage 3 or 4 melanoma that are resistant to existing therapy. 3) Have the presence of measurable lesion. And also have at least one resectable lesion greater than 1 cm in diameter, that only needs 1-2 weeks hospital stay for resection) 4) Be male or female subjects, greater than or equal to 20 years of age and younger than or equal to 65 years of age. 5) Life expectancy of greater than three months. 6) Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1. 7) Major organ function (bone marrow, liver, kidney etc.) ; a) Leukocyte count >=3,000/mm3 b) Number of neutrophils >=1,000/mm3 c) Number of platelets >=100,000/mm3 d) Hemoglobin >=8.0g/dL e) AST and ALT <=150IU/L f) Total bilirubin <=3.0mg/dL g) Creatinine clearance >=30mL/min/1.73m2 8) Have already stopped prior chemotherapy and recovered enough to receive the preparative regimen. 9) Agreed to use an adequate method of contraception within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment. 10) Able to understand and sign the Informed Consent Document.
Key exclusion criteria	1) Have experienced non-myeloablative lymphocyte depleting preparative regimen or myeloablative lymphocyte depleting preparative regimen. 2) Have central nervous system infiltration that causes symptoms. 3) Subjects with intraocular melanoma. 4) Women who are pregnant or breastfeeding. 5) Subjects who take immunosuppressant drugs or adrenocortical steroid*. (*Excluding subjects who had adrenal insufficiency due to anti-PD1 or anti-CTLA4 antibodies therapy, which need steroid replacement dose) 6) Have active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system. 7) Have active other multiple primary malignancies. 8) Have active autoimmune disease. 9) Have a history of severe allergy to cyclophosphamide, fludarabine and IL-2. 10) Left ventricular ejection fraction (LVEF) <=50% 11) Forced expiratory volume in 1 second (FEV1.0%)<=60% 12) Has known history of HBV, HCV, HTLV-1, HIV. 13) Be determined to be ineligible by doctors.
Target sample size	14

Research contact person
Name of lead principal investigator	Takeru Funakoshi
Organization	Keio University School of Medicine
Division name	Department of Dermatology
Address	35 Shinanomachi, Shinjuku-ku, Tokyo, Japan
TEL	+81-3-5363-3823
Email	takeruf@a8.keio.jp

Public contact
Name of contact person	Maki Ishii
Organization	Keio University School of Medicine
Division name	Department of Dermatology
Address	35 Shinanomachi, Shinjuku-ku, Tokyo, Japan
TEL	+81-3-5363-3823
Homepage URL
Email	maki-ishii@keio.jp

Sponsor
Institute	Keio University School of Medicine
Institute
Department

Funding Source
Organization	Keio University School of Medicine
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	2017 Year 11 Month 30 Day

Progress
Recruitment status	Terminated
Date of protocol fixation	2017 Year 11 Month 28 Day
Anticipated trial start date	2018 Year 11 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	2017 Year 11 Month 28 Day
Last modified on	2018 Year 08 Month 09 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034209