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

December 2, 2015 updated by: Jun Guo, Peking University Cancer Hospital & Institute

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Chuanliang Cui, MD
  • Phone Number: 861088196951
  • Email: 1008ccl@163.com

Study Contact Backup

Study Locations

    • Beijing
      • Beijing, Beijing, China, 100142
        • Recruiting
        • Beijing Cancer Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jun Guo, MD,PHD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1(NKT cells single low dose)
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.
autologous natural killer T cell
Experimental: Arm 2(NKT cells single high dose)
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.
autologous natural killer T cell
Experimental: Arm 3(NKT cells multiple dose)
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.
autologous natural killer T cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of subjects experiencing at least one dose limiting toxicity (DLT) of intravenous administration of autologous NKT Cells in metastatic melanoma patients.
Time Frame: 252 days
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.
252 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Jun Guo, MD,PHD, Peking University Cancer Hospital & Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2015

Primary Completion (Anticipated)

October 1, 2016

Study Completion (Anticipated)

October 1, 2017

Study Registration Dates

First Submitted

November 19, 2015

First Submitted That Met QC Criteria

November 30, 2015

First Posted (Estimate)

December 2, 2015

Study Record Updates

Last Update Posted (Estimate)

December 4, 2015

Last Update Submitted That Met QC Criteria

December 2, 2015

Last Verified

December 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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