SentoClone® Compared to Reference Treatment in Advanced Malignant Melanoma

NCT ID: NCT00991250

Last Updated: 2010-02-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2011-09-30

Brief Summary

The purpose of this study is to elucidate whether SentoClone® gives improved treatment responses in patients with advanced malignant melanoma in comparison to established reference treatment(s).

Detailed Description

Malignant melanoma is one of the most common cancer forms worldwide and WHO estimates 132,000 new cases each year. The incidence rate vary up to 150-fold between different regions and ethnicities, the highest rates are found in emigrated Caucasian populations (e.g. Australia and New Zealand).

There are few therapy alternatives for advanced malignant melanomas. At present, dacarbazine (Dacarbazine Medac®) is the most commonly used therapy. Immunotherapy with IL-2 and IFN is an alternative, but it is associated with multiple side effects. Hence, there remains a considerable need for alternative treatments.

By using SentoClone®, autologous tumour-reactive lymphocytes are expanded and infused to the patient, where they have the opportunity to seek out and attack the primary tumour and metastases. The first step is to identify the tumour draining lymph node(s), which is done in parallel to surgical resection of the primary tumour or metastasis. The sentinel and/or metinel node(s), the initial meeting place between tumour antigen and the immune system, are further dissected and collected during the surgery.

In this study SentoClone® will be compared with Dacarbazine Medac® and Temodal® which are currently regarded as standard first-line therapies in advanced malignant melanoma.

Conditions

Malignant Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SentoClone®

SentoClone®: Specific tumour-reactive lymphocytes located in lymph nodes directly draining primary tumours or metastases are identified and expanded. These lymphocytes are infused to the patient to treat metastatic disease.

Group Type: EXPERIMENTAL

SentoClone®

Intervention Type: BIOLOGICAL

SentoClone® are autologous tumour-reactive lymphocytes which are expanded and infused to the patient, where they have the opportunity to seek out and attack the primary tumour and metastases. The first step is to identify the tumour draining lymph node(s), which is done in parallel to surgical resection of the primary tumour or metastasis. The sentinel and/or metinel node(s), the initial meeting place between tumour antigen and the immune system, are further dissected and collected during the surgery. The lymphocytes are extracted from the collected lymph nodes and expanded in vitro, the lymphocytes are thereafter stimulated with tumour extract and returned to the patient intravenously as an autologous cell transfusion. The administered volume will be 100 ml for cell densities less than 3x106 cells/ml and 200 ml for cell densities of 3x106 cells/ml or more.

Temodal® or Dacarbazine Medac®

To be decided by each centre as one of the following:

1. Temodal® (temozolomide)

2. Dacarbazine Medac® (dacarbazine) The reference treatment regimen should follow the general guiding principles for each of the two reference treatments.

Group Type: ACTIVE_COMPARATOR

Temodal® or Dacarbazine Medac®

Intervention Type: DRUG

Dacarbazine (5-[3,3-Dimethyl-1-triazenyl]imidazole-4-carboxamide) is a widely used systemic treatment against advanced malignant melanoma. Dacarbazine is a cytostatic agent, which inhibits tumour growth by interfering with DNA-synthesises. The DNA-synthesis is inhibited by alkylation of the DNA molecule; however, it is unclear whether dacarbazine has other cytostatic impacts on cell mechanisms. Dacarbazine is inactive until liver passage, the liver converts dacarbazine to its reactive metabolites MTIC and HMMTIC, which alkylate DNA. Dacarbazine is light sensitive and needs to be administered intravenously.

A newer analogue to dacarbazine, temozolomide (Temodal®), has been developed for oral administration. Temodal® is administered in capsules and is rapidly absorbed reaching peak concentrations after 20 minutes. Temodal® is converted to MTIC at physiological pH, the same reactive molecule as dacarbazine is metabolized to in the liver.

Interventions

SentoClone®

SentoClone® are autologous tumour-reactive lymphocytes which are expanded and infused to the patient, where they have the opportunity to seek out and attack the primary tumour and metastases. The first step is to identify the tumour draining lymph node(s), which is done in parallel to surgical resection of the primary tumour or metastasis. The sentinel and/or metinel node(s), the initial meeting place between tumour antigen and the immune system, are further dissected and collected during the surgery. The lymphocytes are extracted from the collected lymph nodes and expanded in vitro, the lymphocytes are thereafter stimulated with tumour extract and returned to the patient intravenously as an autologous cell transfusion. The administered volume will be 100 ml for cell densities less than 3x106 cells/ml and 200 ml for cell densities of 3x106 cells/ml or more.

Intervention Type: BIOLOGICAL

Temodal® or Dacarbazine Medac®

Dacarbazine (5-[3,3-Dimethyl-1-triazenyl]imidazole-4-carboxamide) is a widely used systemic treatment against advanced malignant melanoma. Dacarbazine is a cytostatic agent, which inhibits tumour growth by interfering with DNA-synthesises. The DNA-synthesis is inhibited by alkylation of the DNA molecule; however, it is unclear whether dacarbazine has other cytostatic impacts on cell mechanisms. Dacarbazine is inactive until liver passage, the liver converts dacarbazine to its reactive metabolites MTIC and HMMTIC, which alkylate DNA. Dacarbazine is light sensitive and needs to be administered intravenously.

A newer analogue to dacarbazine, temozolomide (Temodal®), has been developed for oral administration. Temodal® is administered in capsules and is rapidly absorbed reaching peak concentrations after 20 minutes. Temodal® is converted to MTIC at physiological pH, the same reactive molecule as dacarbazine is metabolized to in the liver.

Intervention Type: DRUG

Other Intervention Names

DTIC; Dacarbazine; Temozolomide

Eligibility Criteria

Inclusion Criteria

To be eligible for inclusion in this study, the patients must fulfil all of the following criteria:

1. Surgically incurable stage III or IV malignant melanoma

2. At least one measurable lesion

3. WHO performance status 0-1

4. Life expectancy > 3 months

5. Diagnosed metastasis

6. One tumour draining lymph node surgically accessible

7. Measurable tumour manifestation after the harvest of tumour tissue and sentinel/metinel nodes(1)

8. Signed informed consent

(1) Should be fulfilled after surgery (visit 2) for patients randomised to SentoClone®.

Exclusion Criteria

To be eligible for inclusion in this study the patients must not meet any of the following criteria:

1. Known allergy against used trace substance patent blue and/or albumin technetium (Nanocoll) 2. Known allergy against gentamicin and/or phenol red 3. Any condition (medical, social, psychological or legal) that influences adequate information negatively or is considered to be a problem for the patient to cope with treatment and follow-up 4. Aplastic anaemia or myelofibrosis 5. Previous treatment with temozolomide or dacarbazine, or any other chemotherapy during the last 3 months 6. Disease progression following treatment with temozolomide or dacarbazine more than 3 months back(1) 7. Previous radiotherapy of target lesion(s) or tumour draining lymph nodes which will be used for lymphocyte extraction(2) 8. Ongoing systemic steroid treatment or other treatment influencing immune defence 9. History of other malignant tumour disease apart from adequately treated basalioma or squamous cell carcinoma of the skin more than 5 years ago 10. Positive test(s) for HIV and/or Hepatitis B and/or Hepatitis C and/or syphilis 11. Condition or disease which could influence the result of the study or which indicates that the patient runs risks by participating in this study 12. Participation in any other clinical study, involving other investigational methods or products that may influence the results of this trial, within 30 days prior to participating in this trial

1. Patients who responded on the treatment, terminated the treatment at least 3 months prior to the study, and later progressed do not fulfill exclusion criterion 6

2. Irradiated lesions are not considered to be measurable and are therefore not suitable as target lesions. Lesions which have been irradiated but shown progression are considered as measurable.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SentoClone AB

INDUSTRY

Sponsor Role: lead

Responsible Party

SentoClone AB

Principal Investigators

Christian Ingvar, MD

Role: PRINCIPAL_INVESTIGATOR

Lund University Hospital

Locations

Lunds Universitetssjukhus

Lund, Skåne County, Sweden

Site Status: RECRUITING

Södersjukhuset

Stockholm, Stockholm County, Sweden

Site Status: RECRUITING

Karolinska Sjukhuset

Stockholm, Stockholm County, Sweden

Site Status: RECRUITING

Norrlands Universitetssjukhus

Umeå, Västerbotten County, Sweden

Site Status: RECRUITING

Sahlgrenska Universitetssjukhuset

Gothenburg, Västra Götaland County, Sweden

Site Status: NOT_YET_RECRUITING

Countries

Sweden

Facility Contacts

Christian Ingvar, MD

Role: primary

christian.ingvar@skane.se

+46 (0)46-17 10 00

Peter Gillgren, MD

Role: primary

peter.gillgren@sodersjukhuset.se

+46 (0)8-616 23 84

Johan Hansson, MD

Role: primary

johan.hansson@karolinska.se

+46 (0)8-5177 36 40

Peter Naredi, MD

Role: primary

peter.naredi@surgery.umu.se

+46 (0)90- 785 00 00

Jan E Mattsson, MD

Role: primary

jan.e.mattsson@vgregion.se

+46 (0)31-342 84 58

Other Identifiers

EudraCT No: 2008-007515-33

Identifier Type: -

Identifier Source: secondary_id

Mel-Swe-01 2009-12-17

Identifier Type: -

Identifier Source: org_study_id