Phase II/III Clinical Study CSF470 Plus BCG Plus GM-CSF vs IFN Alpha 2b in Stage IIB, IIC and III Melanoma Patients

Study Overview
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Brief Summary
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Randomized, open, Phase II-III study, comparative between treatment with CSF-470 vaccine , allogeneic, irradiated with BCG and molgramostin (rHuGM-CSF) as adjuvants and interferon alfa 2b (IFN-alpha2b) treatment , in stages IIB, IIC o III (AJCC) post-surgery cutaneous melanoma patients. This study has been approved by ANMAT ( Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT)), number 1556/2011 (www.anmat.gov.ar). The study Institution is Instituto Médico Especializado Alexander Fleming, Ciudad Autónoma de Buenos Aires, Argentina. The Sponsor is Laboratory Pablo Cassará (LPC, S.R.L.). Study population include a total of 108 patients (72 patients will receive CSF470 vaccine and 36 patients will receive alpha IFN-alpha 2b) for a total of 24 months. CSF-470 treatment will consist of four vaccine doses id injection (three weeks apart), then one dose every two months for the first year and them every three months for the second year. Each vaccine consist of a mixture of 17,6.106 melanoma cells, from four melanoma cell lines, not genetically modified and lethally irradiated. As adjuvant BCG (120 µg prot) the first day and rHuGM-CSF (Molgramostim, 400 µg, fractionated in four days doses) will be used. IFN-alpha 2b treatment will consist of s.c. injection of 10 million units (MU) (5 t/w ) for four weeks and then 5 MU (3t/w) for 23 months. Both treatments will also compare quality of life (QOL) and study a possible correlation in the CSF470 vaccine arm between the induced immune response and clinical outcome

Official Title
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Randomized, Comparative Phase II/III Study Between Treatment With CSF470 Vaccine (Allogeneic, Irradiated) Plus BCG and MOLGRAMOSTIN (rhGM-CSF) as Adjuvants and Interferon-alfa 2b (IFN-ALPHA), in Stages IIB, IIC and III Post Surgery Cutaneous Melanoma Patients

Conditions
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Cutaneous Melanoma

Intervention / Treatment
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* Biological: CSF470 vaccine, BCG, Molgramostim
* Drug: interferon alpha 2b


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed cutaneous melanoma stages IIB, IIC or III (AJCC) patients non-detectable disease (NED) after surgery as asserted by CAT scans. Melanoma pts with unknown primary tumor site could be included in the study life expectancy > 6 months performance status (ECOG) 0 or 1 Time post surgery not more than 4 months no chemotherapy, radiotherapy or any biological treatments prior to this study. patients must have CATscans of brain, thorax, abdomen and pelvis in the 60 previous days to trial enrolling To have laboratory studies (no more than 15 days before entering the study) laboratory eligibility criteria include: hematocrit: ≥35 (hemoglobin > 10,5 gr %); WBC count > 3500/mm3, platelets > 100.000/mm3, total and direct bilirubin, serum oxalacetic transaminase and glutamic pyruvic transaminase < 1.5 fold the upper normal value; LDH ≤ 450 mU/ml negative serology for HIV, anti-HCV and HBsAg serum creatinine < 2.0 mg % all patients must give written informed consent before inclusion in the Study. Exclusion Criteria: Pregnant or breast-feeding women Diabetes (Type I or II) Antecedents of psychiatric diseases Evidence of active infections Antecedents of viral or autoimmune hepatitis Previous autoimmune diseases Morbid Obesity, defined as CMI (Corporal mass index)>37 kg/m2 in women and >40 kg/m2 in men. Other diseases that require treatment with regular corticoids or non steroids anti-inflammatory drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Interferon alpha 2 b<br>Interferon alpha 2b treatment will consist of s.c. injection of 10 MU (5 t/w) for four weeks and then 5 MU (3t/w) for 23 months. | Drug: interferon alpha 2b<br> <br> |
| Experimental: CSF470 vaccine, BCG, Molgramostim<br>CSF470 vaccine, BCG, Molgramostim CSF-470 treatment will consist of four vaccine doses id injection (three weeks apart), then one dose every two months for the first year and them every three months for the second year. Each vaccine consist of a mixture of 17,6.106 melanoma cells , from four melanoma cell lines, not genetically modified and lethally irradiated. As adjuvant BCG (120 µg prot) the first day and rhGM-CSF (Molgramostim 400 µg, fractionated in four days doses) will be used. | Biological: CSF470 vaccine, BCG, Molgramostim<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | OS, DFS, Partial or total remission (PR or CR) | two years | 
| security | measured according to the NCI-Common Toxicity Criteria | two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life | QOL:evaluated with EORTC QLQ-C30 questionnaire; ECOG Performance status | two years | 
| Induction of immune responses | Induction of immune responses associated to different vaccine doses for 2 years (Trial duration) ]Cellular immunity (DTH) - Humoral immunity | two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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melanoma, irradiated-allogeneic cells, therapeutic vaccine, Interferon alpha 2-b