stage III/IV melanoma in patients who are free from measurable tumor lesions following the local treatment of macro metastases MedDRA version: 13.1 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 13.1 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cy
Conditions
Interventions
Product Name: TriMix-DC
Product Code: TriMix-DC
Pharmaceutical Form: Solution for injection/infusion in pre-filled syringe
INN or Proposed INN: TriMix-DC
Current Sponsor code: TriMix-DC
Other descript
Sponsors
UZ BRUSSEL
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able and willing to give valid written informed consent before undergoing any study-related activities; patients must be willing to cooperate for the whole period of the study, and accept to be treated according to the study protocol regardless of the study arm the patient is allocated to following the randomization step; 2. Histological documentation of AJCC stage III (Tx, N1b,-2b,-2c or -3, M0), or stage IV melanoma; 3. Primary melanoma of the skin, unknown primary; patients with primary mucosal, or uveal melanoma (melanoma originating in the choroid, iris or ciliar body) are not eligible; 4. At baseline tumor assessment by whole-body FDG-PET/CT, patients should be free from measurable tumor lesions (measurability is defined according to RECIST (v1.1)), and free from symptomatic non-measurable tumor lesions (e.g. bone metastasis, or pleural effusion); 5. Prior local treatment of primary and metastatic tumor lesions is allowed (e.g. surgical resection, isolated limb perfusion, radiofrequency ablation, radiotherapy, cryotherapy, …). Treated tumor lesions should be free from progression at baseline assessment; 6. Normal organ function and normal hematological parameters (as reflected by blood values); baseline laboratory parameters should be within normal range, except for the following laboratory parameters, which must be within the ranges specified: BLOOD PARAMETER RANGE HEMOGLOBIN = 10 G/DL GRANULOCYTES = 1,500/µL LYMPHOCYTES = 500/µL PLATELETS = 100,000/µL SERUM CREATININ = 2.0 MG/DL SERUM BILIRUBIN = 2.0 MG/DL AST AND ALT = 2 X THE NORMAL UPPER LIMITS LDH = 1,5X NORMAL UPPER LIMIT CRP = 1,5X NORMAL UPPER LIMIT PROTHROMBIN TIME (PT) INTERNATIONAL NORMALIZED RATIO (INR) AND PARTIAL THROMBOPLASTIN TIME (PTT) WITHIN NORMAL LIMITS 7. Negative serology for HCV, and HIV; absence of active infection with HBV, and Syphilis; If positive results for HepB or Syphilis indicate immunity and are not indicative of active infection, the patient can enter the study. 8. Adequate venous access that allows to undergo leukapheresis; 9. No prior systemic therapy for melanoma; 10. Full recovery from all prior therapies. A minimal period of 4 weeks following major surgery, radiation therapy, or ILP, or any other major invasive procedure is required; 11. Baseline WHO performance status of 0, or 1 (see Appendix D); 12. Male and female patients = 18 years of age; 13. No need for uninterrupted therapeutic anticoagulation (e.g. for recent thrombo-embolism, or cardiac valve prosthesis) 14. No prior history of a serious autoimmune disorder 15. No concomitant medication with immune suppressive drugs (e.g. oral corticosteroids). 16. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea = 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35mIU/mL]. Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where pa
Exclusion criteria
Exclusion criteria: 1. Evidence of immunodeficiency. Autoimmune disease requiring medical treatment (e.g. corticosteroids or other immunosuppressive drugs). Vitiligo (skin depigmentation) is not an exclusion criterion; 2. Any serious acute or chronic illnesses (e.g. heart disease NYHA Class III or IV, renal-, liver- or pulmonary insufficiency) or other conditions requiring concurrent medications not allowed during this study (e.g. active chronic infections requiring antibiotics). 3. History of malignancy. Subjects with curatively treated cervical carcinoma in situ, or squamous-, or basal cell carcinoma of the skin, or subjects who have been treated and recurrence-free of other malignancies for ? 5 years following the diagnosis are eligible for this study; 4. Inability to undergo FDG-PET/CT, or MRI examination; 5. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study; 6. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment; 7. Subject is pregnant (positive serum beta human chorionic gonadotropin [?-HCG] test at screening) or is currently breast-feeding, anticipates becoming pregnant/ impregnating their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessar, condoms or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment; 8. Current alcohol dependence or drug abuse; 9. Known hypersensitivity to the study treatment; 10. Legal incapacity or limited legal capacity; 11. Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. 12. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the disease-free survival following therapeutic administration of autologous mRNA-electroporated monocyte derived DC in patients with stage III/IV melanoma who are free from measurable tumor lesions following the local treatment of macrometastases (e.g. by surgical resection, isolated limb perfusion, radiofrequency ablation, radiotherapy, …).;Secondary Objective: Applicable to both arms of the study: 1. To document the feasibility of manufacturing, and the product characteristics of the cellular IATMP (: autologous mRNA electroporated monocyte derived DC); 2. To document the safety, and feasibility of therapeutic administration of autologous mRNA electroporated monocyte derived DC; 3. To determine the recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) using Kaplan-Meier survival estimates; Applicable to Arm B of the clinical trial only: 4. To determine the best objective response according to the RECIST (v1.1), and the immune-related response criteria (irRC); 5. To determine the progression-free survival (PFS) according to the RECIST (V1.1), and immune-related response criteria (irRC) using Kaplan-Meier survival estimates. ;Primary end point(s): percentage of patients who are alive and free from melanoma macrometastases at 1 year (: 52 weeks) following randomization.;Timepoint(s) of evaluation of this end point: Week 52 following the initiation of study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Applicable to both arms of the study: 1. the IATMP will be characterized for: the number of DC, purity and viability, electroporation efficiency (measured by the % of cells expressing CD70), the immunophenotype (including CD40, CD80, CD83, CCR7, CD14 expression), and functional characterization by IL-12p70 secretion at 0-24h and 24-48h. DC samples will be analyzed for sterility by long-term microbiological culture. The results will be tabulated, analyzed and summarized using descriptive statistics. 2. Safety will be evaluated for all treated patients using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Safety assessments will be based on medical review of adverse event (AE) reports and the results of vital sign measurements, physical examinations and clinical laboratory tests. The incidence of AEs will be tabulated and reviewed for potential significance and clinical importance. The reporting period for safety data will be from the date of the first leukapheresis until the end of study visit. 3. time of recurrence (locoregional and/or distant), time of death; median values with 95% confidence intervals will be determined using Kaplan-Meier survival estimates; Applicable to Arm B of the clinical trial only: Secondary endpoints: time of progression (according to irRC, and RECIST), or death. ;Timepoint(s) of evaluation of this end point: Continuous during the conduct of the study | — |
Countries
Belgium
Contacts
Public ContactProf Bart Neyns
UZ Brussel
Outcome results
None listed