UMIN-CTR Clinical Trial

Public title

Phase 1/2 study of adoptive cell therapy using cultured tumor infiltrating lymphocytes with lympho-depleting non-myeloablative preconditioning for patients with advanced melanoma

Acronym

MM-TIL-P1/2

Scientific Title

Phase 1/2 study of adoptive cell therapy using cultured tumor infiltrating lymphocytes with lympho-depleting non-myeloablative preconditioning for patients with advanced melanoma

Scientific Title:Acronym

MM-TIL-P1/2

Region

Japan

Condition

Advanced malignant melanoma

Classification by specialty

Dermatology

Classification by malignancy

Malignancy

Genomic information

NO

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

Primary outcomes

Overall response rate, Safety

Key secondary outcomes

Duration response, Duration of stable disease, Progression-free survival, Overall survival

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Takeru Funakoshi

Organization

Keio University School of Medicine

Division name

Department of Dermatology

Zip code

Address

35 Shinanomachi, Shinjuku-ku, Tokyo, Japan

TEL

+81-3-5363-3823

Email

takeruf@a8.keio.jp

Name of contact person

1st name
Middle name
Last name	Maki Ishii

Organization

Keio University School of Medicine

Division name

Department of Dermatology

Zip code

Address

35 Shinanomachi, Shinjuku-ku, Tokyo, Japan

TEL

+81-3-5363-3823

Homepage URL

Email

maki-ishii@keio.jp

Institute

Keio University School of Medicine

Institute

Department

Personal name

Organization

Keio University School of Medicine

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2017

Year

11

Month

30

Day

URL releasing protocol

Publication of results

Unpublished

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

Recruitment status

Terminated

Date of protocol fixation

2017

Year

11

Month

28

Day

Date of IRB

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

Other related information

Registered date

2017

Year

11

Month

28

Day

Last modified on

2018

Year

08

Month

09

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034209