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A Clinical Trial of Adoptive Transfer With Autologous NKT Cells in Metastatic Melanoma Patients

Primary Purpose

Melanoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

NKT cells

About this trial

This is an interventional treatment trial for Melanoma focused on measuring NKT, metastatic melanoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must have pathological or cytologically confirmed malignant melanoma with unresectable Stage III or Stage IV (including skin and distant lymph node metastasis M1a, lung metastasis M1b).
Patients who are resistant /refractory to approved therapies, or for whom no curative therapies are available.
Male or female, aged ≥18 and ≤70 years; ECOG performance status score of 0-2; Life expectancy of at least six months.
For women of childbearing potential, a negative pregnancy test within 7 days prior to the first treatment.
At least four weeks since prior other anti-tumor therapy, including endocrine, chemotherapy/radiotherapy and targeted therapy, at least six weeks since prior nitrosourea and mitomycin dosing, and have recovered from the adverse reactions due to prior therapy.
At least 4 weeks before prior surgery.
Must have one measurable or evaluable lesion according to RECIST 1.1
With enough tumor tissues and diagnosed by the designated laboratory.
Body weight >50kg.
Without functional disorder of major organs ( laboratory examination): Neutrophils≥1.5×10^9/L, lymphocyte≥1.0×10^9/L, PLT≥100×10^9/L, Hb≥110g/L; BUN and Cr within normal range; TBIL≤1.5 times upper limit; ALT/AST≤2.5 times upper limit; PT/APTT within normal range.
Without obvious hereditary disease.
Must sign a written informed consent form prior to entering the study, with good compliance.

Exclusion Criteria:

With extrapulmonary metastatic of melanoma, for instance, distant metastasis of liver, brain, bone, adrenal gland.
With serious internal disease, including serious heart disease, cerebral vascular disease, uncontrolled diabetes, uncontrolled hypertension, serious infections, active peptic ulcer, renal failure and respiratory failure.
Uncontrolled infectious diseases or other serious diseases, for example, HIV, Hepatitis B and Hepatitis C.
Uncontrolled brain metastases.
Lymphoma or leukemia patients.
Patients who have received bone marrow, stem cells or organ transplantation.
With immunodeficiency or autoimmune disease, leucoderma excluded.
Allergic constitution.
Chronic diseases needed immunosuppressive therapy or hormone therapy.
Patients treated with steroid hormone.
Unable to evaluate the immune status, or patients cannot comply with follow-up clinical evaluation.
Patients diagnosed with MDS (myelodysplastic syndromes).
Patients who are pregnant or breast-feeding.
Women (or patients' wife) of child-bearing without effective contraceptive measures.
Patients receiving any investigational drug or investigational treatment within 4 weeks prior to first dosing.
With uncontrolled mental disorders.

Sites / Locations

Beijing Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Arm 1（NKT cells single low dose）

Arm 2（NKT cells single high dose）

Arm 3（NKT cells multiple dose）

Arm Description

Patients will receive intravenous administration of autologous NKT cells, the dose level is 1×10^9 on d1, 2×10^9 on d3, 4×10^9 on d29, 8×10^9 on d31.

Patients will receive intravenous administration of autologous NKT cells, the dose level is 5×10^9 on d1, 5×10^9 on d3, 5×10^9 on d29, 5×10^9 on d31.

Patients will receive intravenous administration of autologous NKT cells, the dose level is 5×10^9 on d1, 5×10^9 on d3 of each 28 days-cycle, the dosing will be ended after 8 cycles.

Outcomes

Primary Outcome Measures

Number of subjects experiencing at least one dose limiting toxicity (DLT) of intravenous administration of autologous NKT Cells in metastatic melanoma patients.

DLT is defined as any of the following toxicities assessed as at least possibly related to NKT cells by the investigator up to 28 days each cycle(up to 8 cycles,with 28 days' safety and efficacy follow-up after the end of the last cycle) after the end of adoptive transfer: any Grade greater than or equal to (>=) 3 non-hematological toxicity, but excluding the conditions mentioned in the protocol; any Grade 4 neutropenia of greater than (>)5 days duration or Grade >=3 febrile neutropenia; any Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding; any Grade 4 anemia.

Secondary Outcome Measures

Full Information

NCT ID

NCT02619058

First Posted

November 19, 2015

Last Updated

December 2, 2015

Sponsor

Peking University Cancer Hospital & Institute

1. Study Identification

Unique Protocol Identification Number

NCT02619058

Brief Title

A Clinical Trial of Adoptive Transfer With Autologous NKT Cells in Metastatic Melanoma Patients

Official Title

An Open Label, Dose Escalation, Phase I Clinical Trial of Adoptive Transfer With Autologous NKT Cells in Metastatic Melanoma Patients

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Unknown status

Study Start Date

October 2015 (undefined)

Primary Completion Date

October 2016 (Anticipated)

Study Completion Date

October 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking University Cancer Hospital & Institute

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Considerable progress in the treatment of metastatic melanoma has been made in the past 5years, with the approval of immune checkpoint-blocking antibodies and agents targeting BRAF mutation. Investigators conducted a open label, dose escalation, phase I clinical trial of to explore the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of intravenous administration of autologous NKT Cells in metastatic melanoma patients.

Detailed Description

Considerable progress in the immunotherapy of metastatic melanoma has been made in the past 5 years, with the approval of immune checkpoint-blocking antibodies. NKT cells are a potent immunoregulatory cell population heavily implicated in promoting immunity to infection and cancer. And now with new generation of amplification method, more than 1,000 folds amplification of NKT cells can be obtained, so NKT cell based adoptive cell transfer is now available and might show its efficacy in melanoma. Investigators conducted this open label, dose escalation, phase I clinical trial of to explore the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of intravenous administration of autologous NKT Cells in metastatic melanoma patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

Keywords

NKT, metastatic melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm 1（NKT cells single low dose）

Arm Type

Experimental

Arm Description

Patients will receive intravenous administration of autologous NKT cells, the dose level is 1×10^9 on d1, 2×10^9 on d3, 4×10^9 on d29, 8×10^9 on d31.

Arm Title

Arm 2（NKT cells single high dose）

Arm Type

Experimental

Arm Description

Patients will receive intravenous administration of autologous NKT cells, the dose level is 5×10^9 on d1, 5×10^9 on d3, 5×10^9 on d29, 5×10^9 on d31.

Arm Title

Arm 3（NKT cells multiple dose）

Arm Type

Experimental

Arm Description

Patients will receive intravenous administration of autologous NKT cells, the dose level is 5×10^9 on d1, 5×10^9 on d3 of each 28 days-cycle, the dosing will be ended after 8 cycles.

Intervention Type

Biological

Intervention Name(s)

NKT cells

Intervention Description

autologous natural killer T cell

Primary Outcome Measure Information:

Title

Number of subjects experiencing at least one dose limiting toxicity (DLT) of intravenous administration of autologous NKT Cells in metastatic melanoma patients.

Description

Time Frame

252 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must have pathological or cytologically confirmed malignant melanoma with unresectable Stage III or Stage IV (including skin and distant lymph node metastasis M1a, lung metastasis M1b). Patients who are resistant /refractory to approved therapies, or for whom no curative therapies are available. Male or female, aged ≥18 and ≤70 years; ECOG performance status score of 0-2; Life expectancy of at least six months. For women of childbearing potential, a negative pregnancy test within 7 days prior to the first treatment. At least four weeks since prior other anti-tumor therapy, including endocrine, chemotherapy/radiotherapy and targeted therapy, at least six weeks since prior nitrosourea and mitomycin dosing, and have recovered from the adverse reactions due to prior therapy. At least 4 weeks before prior surgery. Must have one measurable or evaluable lesion according to RECIST 1.1 With enough tumor tissues and diagnosed by the designated laboratory. Body weight >50kg. Without functional disorder of major organs ( laboratory examination): Neutrophils≥1.5×10^9/L, lymphocyte≥1.0×10^9/L, PLT≥100×10^9/L, Hb≥110g/L; BUN and Cr within normal range; TBIL≤1.5 times upper limit; ALT/AST≤2.5 times upper limit; PT/APTT within normal range. Without obvious hereditary disease. Must sign a written informed consent form prior to entering the study, with good compliance. Exclusion Criteria: With extrapulmonary metastatic of melanoma, for instance, distant metastasis of liver, brain, bone, adrenal gland. With serious internal disease, including serious heart disease, cerebral vascular disease, uncontrolled diabetes, uncontrolled hypertension, serious infections, active peptic ulcer, renal failure and respiratory failure. Uncontrolled infectious diseases or other serious diseases, for example, HIV, Hepatitis B and Hepatitis C. Uncontrolled brain metastases. Lymphoma or leukemia patients. Patients who have received bone marrow, stem cells or organ transplantation. With immunodeficiency or autoimmune disease, leucoderma excluded. Allergic constitution. Chronic diseases needed immunosuppressive therapy or hormone therapy. Patients treated with steroid hormone. Unable to evaluate the immune status, or patients cannot comply with follow-up clinical evaluation. Patients diagnosed with MDS (myelodysplastic syndromes). Patients who are pregnant or breast-feeding. Women (or patients' wife) of child-bearing without effective contraceptive measures. Patients receiving any investigational drug or investigational treatment within 4 weeks prior to first dosing. With uncontrolled mental disorders.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Chuanliang Cui, MD

Phone

861088196951

1008ccl@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Jun Guo, MD,PHD

Phone

861088196317

guoj307@126.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jun Guo, MD,PHD

Organizational Affiliation

Peking University Cancer Hospital & Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Beijing Cancer Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100142

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Chuanliang Cui, MD

Phone

0086-10-88196951

1008ccl@163.com

First Name & Middle Initial & Last Name & Degree

Jun Guo, MD,PHD

Phone

0086-10-88196317

guoj307@126.com

First Name & Middle Initial & Last Name & Degree

Jun Guo, MD,PHD

12. IPD Sharing Statement

Citations:

PubMed Identifier

19097774

Citation

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

Results Reference

background

PubMed Identifier

17198079

Citation

Hoos A, Parmiani G, Hege K, Sznol M, Loibner H, Eggermont A, Urba W, Blumenstein B, Sacks N, Keilholz U, Nichol G; Cancer Vaccine Clinical Trial Working Group. A clinical development paradigm for cancer vaccines and related biologics. J Immunother. 2007 Jan;30(1):1-15. doi: 10.1097/01.cji.0000211341.88835.ae.

Results Reference

background

PubMed Identifier

19934295

Citation

Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbe C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009 Dec 1;15(23):7412-20. doi: 10.1158/1078-0432.CCR-09-1624. Epub 2009 Nov 24.

Results Reference

background

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A Clinical Trial of Adoptive Transfer With Autologous NKT Cells in Metastatic Melanoma Patients

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