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

Primary Purpose

Cutaneous Melanoma

Status

Unknown status

Phase

Phase 2

Locations

Argentina

Study Type

Interventional

Intervention

CSF470 vaccine, BCG, Molgramostim

interferon alpha 2b

About this trial

This is an interventional treatment trial for Cutaneous Melanoma focused on measuring melanoma, irradiated-allogeneic cells, therapeutic vaccine, Interferon alpha 2-b

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Instituto Médico Alexander FlemingRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Interferon alpha 2 b

CSF470 vaccine, BCG, Molgramostim

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Efficacy

OS, DFS, Partial or total remission (PR or CR)

security

measured according to the NCI-Common Toxicity Criteria

Secondary Outcome Measures

Quality of Life

QOL:evaluated with EORTC QLQ-C30 questionnaire; ECOG Performance status

Induction of immune responses

Induction of immune responses associated to different vaccine doses for 2 years (Trial duration) ]Cellular immunity (DTH) - Humoral immunity

Full Information

NCT ID

NCT01729663

First Posted

November 14, 2012

Last Updated

August 31, 2015

Sponsor

Laboratorio Pablo Cassará S.R.L.

Collaborators

Fundacion Sales, National Agency for Scientific and Technological Promotion, Argentina, Fundacion Cancer FUCA, National Council of Scientific and Technical Research, Argentina, Instituto Nacional del Cáncer, Argentina

1. Study Identification

Unique Protocol Identification Number

NCT01729663

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2015

Overall Recruitment Status

Unknown status

Study Start Date

April 2009 (undefined)

Primary Completion Date

December 2018 (Anticipated)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Laboratorio Pablo Cassará S.R.L.

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

6. Conditions and Keywords

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

Cutaneous Melanoma

Keywords

melanoma, irradiated-allogeneic cells, therapeutic vaccine, Interferon alpha 2-b

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

108 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Interferon alpha 2 b

Arm Type

Active Comparator

Arm Description

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.

Arm Title

CSF470 vaccine, BCG, Molgramostim

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

CSF470 vaccine, BCG, Molgramostim

Intervention Type

Drug

Intervention Name(s)

interferon alpha 2b

Primary Outcome Measure Information:

Title

Efficacy

Description

OS, DFS, Partial or total remission (PR or CR)

Time Frame

two years

Title

security

Description

measured according to the NCI-Common Toxicity Criteria

Time Frame

two years

Secondary Outcome Measure Information:

Title

Quality of Life

Description

QOL:evaluated with EORTC QLQ-C30 questionnaire; ECOG Performance status

Time Frame

two years

Title

Induction of immune responses

Description

Induction of immune responses associated to different vaccine doses for 2 years (Trial duration) ]Cellular immunity (DTH) - Humoral immunity

Time Frame

two years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

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

José Mordoh, MD, PhD

Phone

54-11-6323-2900

Ext

2205

jmordoh@alexanderfleming.org

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

María M Barrio, PhD

Phone

54-11-6323-2900

Ext

1110

barrio.marcela@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

José Mordoh, MD, PhD

Organizational Affiliation

Instituto Médico Alexander Fleming

Official's Role

Principal Investigator

Facility Information:

Facility Name

Instituto Médico Alexander Fleming

City

Buenos Aires

State/Province

Capital Federal

ZIP/Postal Code

1426

Country

Argentina

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

José Mordoh, MD, PhD

Phone

44-11-6323-2900

Ext

2204

jmordoh@leloir.org.ar

First Name & Middle Initial & Last Name & Degree

José Mordoh, MD, PhD

First Name & Middle Initial & Last Name & Degree

María M Barrio, PhD

12. IPD Sharing Statement

Citations:

PubMed Identifier

29774030

Citation

Aris M, Bravo AI, Pampena MB, Blanco PA, Carri I, Koile D, Yankilevich P, Levy EM, Barrio MM, Mordoh J. Changes in the TCRbeta Repertoire and Tumor Immune Signature From a Cutaneous Melanoma Patient Immunized With the CSF-470 Vaccine: A Case Report. Front Immunol. 2018 May 3;9:955. doi: 10.3389/fimmu.2018.00955. eCollection 2018.

Results Reference

derived

PubMed Identifier

28620382

Citation

Mordoh J, Pampena MB, Aris M, Blanco PA, Lombardo M, von Euw EM, Mac Keon S, Yepez Crow M, Bravo AI, O'Connor JM, Orlando AG, Ramello F, Levy EM, Barrio MM. Phase II Study of Adjuvant Immunotherapy with the CSF-470 Vaccine Plus Bacillus Calmette-Guerin Plus Recombinant Human Granulocyte Macrophage-Colony Stimulating Factor vs Medium-Dose Interferon Alpha 2B in Stages IIB, IIC, and III Cutaneous Melanoma Patients: A Single Institution, Randomized Study. Front Immunol. 2017 May 31;8:625. doi: 10.3389/fimmu.2017.00625. eCollection 2017.

Results Reference

derived

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

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