Combined Therapy of Nivolumab and Adoptive T Cell Therapy in Metastatic Melanoma Patients

NCT03374839 | Unknown Phase 1 DMC

• 1 other identifier: RC15_0247
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

To improve the efficacy of immunotherapy for cancer, recent studies focused on specific targets to redirect the immune network toward eradicating a variety of tumors and ameliorating the self-destructive process. A clinically relevant immune escape mechanism in melanoma is the activation of the Programmed cell Death-1 (PD-1) receptor on infiltrating T cells. By blocking PD-1 receptors with anti-PD-1 monoclonal antibodies (mAbs), T-cells are unaffected by the PD-L1 expressed on tumor cells and the patients T cells are free to respond to melanoma antigens and attack tumor cells. So the objective of this trial is to evaluate the safety and the efficacy of a combined therapy Nivolumab and adoptive T cell therapy in metastatic melanoma patients.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment (adoptive T cell therapy associated to intravenous injections of Nivolumab) - Emergent Adverse Events

  Clinical and biological criteria defined by the NCI (Common Terminology Criteria for Adverse Events - version 4.0, may 2009, http://ctep.cancer.gov)

  Within 12 months

Secondary Outcomes (17)

• Efficacy of adoptive T cell therapy associated to intravenous injections of Nivolumab

  At 12 months

• Duration of the clinical response

  Within 12 months of follow-up

• Progression-free survival

  From the date of the first infusion of Nivolumab until the date of the first documented progression or the date of death from any cause, whichever came first, assessed up to 12 months

• Overall survival

  From the date of the first infusion of Nivolumab until the date of death, assessed up to 12 months

• Specific immune monitoring n°1: Evaluate the fraction of TIL specific to Melan-A and MELOE-1

  Week 14 + week 18

Study Arms (1)

TIL + IL-2 + Nivolumab

EXPERIMENTAL

A first cohort of 3 patients will be done to ensure that the combined treatment (TIL + IL-2 + Nivolumab) would not cause severe autoimmunity pathologies. For this first cohort, a dose of 0.5 billion of TILs per injection will be administered. After the opinion of the Data and Safety Monitoring Committee (DSMC), the sponsor will make the decision of the second cohort of 8 patients who will receive between 1 and 20 billion of TIL.

Drug: TIL + IL-2 + Nivolumab

Interventions

TIL + IL-2 + Nivolumab DRUG

The patients will receive Nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks from day0 until week52. Two TIL (Tumor Infiltrating Lymphocytes) injections will be performed: at week 14 and at week 18. The TIL injections are systematically followed by subcutaneous injections of Proleukin® (IL-2) at a concentration of 6 million international unit (IU) per day for 5 days.

TIL + IL-2 + Nivolumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• over 18 years old with a weight ≥ 40 kg
• Patients must have signed informed consent
• Patients with stage IIIb, IIIc or IV metastatic melanoma (AJCC 6th edition) with at least two lesions (lymph nodes relapse, or in transit metastasis, or unresectable cutaneous metastases, or visceral metastases except bone and brain metastases) including one easily accessible and no more than 2 lines of treatment of melanoma at the metastatic stage.
• Patients with a melanoma expressing a Braf V600 mutation can be included
• Measurable/assessable disease in 28 days which precede the first administration of the treatment
• A negative pregnancy test for women with childbearing potential
• Eastern Cooperative Oncology Group (ECOG) of 0-1, Karnofsky \> 80%
• Laboratory results:
• Haemoglobin ≥ 10 g/dl or ≥ 6,25 mmol/l; Neutrophils ≥ 1500/μl; Leukocytes ≥ 4000/μl; Lymphocytes ≥ 700/μl; Blood platelet ≥ 100.000/μl; Serum creatinine ≤ 1.5 x superior normal value or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula); Serum bilirubin ≤ 2.0 mg/dl or ≤ 34.2 mol/l; Total bilirubin ≤ 1.5 x superior normal value (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3mg/dL); Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2 x superior normal value; Lactate dehydrogenase (LDH) ≤ 1.5 x superior normal value
• Subjects affiliated to an appropriate health insurance
• Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception during the clinical trial. Furthermore WOCBP will be instructed to adhere to contraception for a period of 5 months after the last dose of Nivolumab.
• Men who are sexually active with WOCBP will be instructed to adhere to contraception during the clinical trial and for a period of 7 months after the last dose of Nivolumab.
• Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception.
• Brain or bone metastases
• Ocular melanoma

You may not qualify if:

• \* Positive viral serology for HIV (human immunodeficiency virus) 1/2, p24 Ag, HTLV1, HTLV2, B and C hepatitis or syphilis

Sponsors & Collaborators

• Nantes University Hospital: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Nantes University Hospital

Nantes, 44000, France

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

Toll-Like Receptor 1; Interleukin-2; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Toll-Like Receptors; Receptors, Pattern Recognition; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Lymphokines; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Central Study Contacts

Amir Khammari, PhD

CONTACT

(+33) (0)2 40 08 32 80; amir.khammari@chu-nantes.fr

Brigitte Dréno, MD, PhD

CONTACT

brigitte.dreno@wanadoo.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2017
• First Posted: December 15, 2017
• Study Start: February 12, 2018
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: May 6, 2022

Record last verified: 2022-05

Locations

FR (1)