Malignant MelanomaPhase 2NCT00350597
GM-CSF as Adjuvant Therapy of Melanoma
A Phase 2 study testing Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in people with Malignant Melanoma, run by Northern California Melanoma Center at 1 site in United States.
Trial summary
This is a pilot study to describe the immunological responses and clinical outcome associated with administration of recombinant human Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) as surgical adjuvant therapy in patients with malignant melanoma who are at high risk for recurrence (Stage II T4, III and IV). Read more about this study
- Who is it for?
- Ages 14 years and older
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2004to Jul 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Eligible patients will be males or females with histologically proven melanoma. Patients must have Stage II (T4), III, and IV malignant melanoma surgically resected with no clinical evidence of disease by clinical, laboratory criteria or radiologic examination as defined below.
- Individuals must be at least 14 years of age.
- Pregnant women are not eligible. Men and women will be required to use an effective form of contraception.
- Patients requiring corticosteroid therapy or are receiving other forms of immunotherapy are not eligible.
- Patients may have received immunotherapy for prior disease. They must have completed therapy at least one month prior to study entry. Patients may not have received prior chemotherapy or therapy with GM-CSF. Patients are permitted to receive adjuvant radiation therapy but these patients will not be selected as part of the sub-set undergoing studies of cellular immunologic responses since the radiation could alter these responses. Based on the reults from one randomized, controlled clinical trial, the LEUKINE product labeling contains the following contraindication: "Due to the potential sensitivity of rapidly dividing hematopoietic progenitor cells, LEUKINE should not be administered simultaneously with cytoxic chemotherapy or radiotherapy or within 24 hours preceding or following chemotherapy or radiotherapy. In one controlled study, patients with small cell lung cancer received LEUKINE and concurrent thoracic radiotherapy and chemotherapy or the identical radiotherapy and chemotherapy without LEUKINE. The patients randomized to LEUKINE had significantly higher incidence of adverse events, including higher mortality and a higher incidence of grade 4 infections and grade 3 or 4 thrombocytopenia.28" Other investigators have reported that CM-CSF can be given safely with concurrent radiation therapy. These contrasting results may be related to differences in the patient populations or intensity and/or location of the site of radiotherapy in the body, among other factors. GM-CSF has been administered safely in combination with radiation therapy for treatment of head and neck cancers29,30 and has been used safely during regimens that combine chemotherapy and radiation therapy.31
- Patients must undergo examination for evidence of residual disease, including physical examination, CBC, chemistry panel, CT scan of the chest and abdomen (and pelvis for lower extremity or lower trunk lesions), and single sequence with gadolinium MRI or CT of the brain. A PET scan may be substituted for the CT of the chest and abdomen (and pelvis). These tests must be negative for residual disease before entry into the study.
- Administration of the protocol medication must be initiated within 90 days of the definitive surgical excision rendering the patient NED.
Who cannot join
- Patients not meeting Inclusion Criteria described above
Trial locations and contacts
1 site in 1 country.
United States1 site
Northern California Melanoma Center
San Francisco, California, 94109
About this study
Official title: Immunologic and Antibody Responses in Patients Receiving GM-CSF, (Leukine, Sargramostim) as Adjuvant Therapy of Stage II (T4), III and IV Melanoma.
This is a pilot study to describe the immunological responses and clinical outcome associated with administration of recombinant human Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) as surgical adjuvant therapy in patients with malignant melanoma who are at high risk for recurrence (Stage II T4, III and IV).
Read the detailed description
This is a pilot study to describe the immunological responses and clinical outcome associated with administration of recombinant human Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) as surgical adjuvant therapy in patients with malignant melanoma who are at high risk for recurrence (Stage II T4, III and IV). The immunological responses include serum neopterin levels. In a sub-set of study participants, additional immunologic testing will be done, including monocyte cytotoxicity to a melanoma cell line and phenotypic and functional markers of dendritic and T cell activation in peripheral blood mononuclear cells. The clinical end points of the study include safety, time to disease recurrence, time to disseminated disease, and survival. Eligible patients are those with high-risk melanoma who are clinically tumor free following surgery. Treatment will consist of GM-CSF at 125 g/m2 once daily (maximum dose 250 g) for 14 days followed by 14 days of rest (28 day cycle) for 1 year. Clinical status will be monitored until death or until the patient has been tumor free for five years, whichever event occurs first. Immunologic responses will be determined pretreatment, at the end of the first 14 days of dosing (Day 15), after the 14-day rest period (Day 29) and at the end of 14 days of dosing in cycles 6 (Day 155) and 13 (Day 351). Clinical outcome will be determined according to patient risk group (ultra-high risk Stage IIIC or IV versus high-risk Stage II T4, Stage IIIA and Stage IIIB). The pilot study will also assess the association of the immunological responses with clinical response and safety by patient risk group.
- Conditions
- Malignant Melanoma
- Being tested
- Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
- Keywords
- Malignant Melanoma, Adjuvant Therapy, Cytokine Therapy, Immunologic Testing
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
1 To describe the effect of GM-CSF adjuvant treatment of 125 ug/m2 once daily for 14 days followed by 14 days rest on immunological function as determined by serum neopterin levels (a measure of macrophage activation) and on serum levels of S100B.
Secondary outcomes (5)
To evaluate if a change of any or all of the immunological parameters over the treatment period is associated with safety and/or clinical outcome as measured by time to disease recurrence, time to disseminated disease and/or survival.
To perform a more detailed immunologic analysis in a sub-set of study participants (6 evaluable patients) to determine the immunologic responses induced by GM-CSF. There are three main immunological analyses to be determined:
a Monocyte cell numbers and activity
b Mature dendritic cell numbers
c Surface markers on peripheral blood mononuclear cells (PBMC) relative to T cells
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2006 (estimated)
- Study startSep 2004
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants
Sponsor and investigators
- Lead sponsor
- Northern California Melanoma Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer, Melanoma Research Institute
- Investigators
- Lynn E. Spitler, MD, Principal investigator, Northern California Melanoma Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00350597
- Sponsor's protocol ID
- GM-CSF 040906
- Status last verified
- Jul 2006
- First submitted
- 10 Jul 2006
- Last updated
- 11 Jul 2006
- Results posted
- No
Publications
Spitler LE, Grossbard ML, Ernstoff MS, Silver G, Jacobs M, Hayes FA, Soong SJ. Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor. J Clin Oncol. 2000 Apr;18(8):1614-21. doi: 10.1200/JCO.2000.18.8.1614.
PubMed 10764421
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunologic and Antibody Responses in Patients Receiving GM-CSF, (Leukine, Sargramostim) as Adjuvant Therapy of Stage II (T4), III and IV Melanoma.
- ClinicalTrials.gov ID
- NCT00350597
- Acronym / sponsor ID
- GM-CSF 040906
- Conditions
- Malignant Melanoma
- Keywords
- Malignant Melanoma, Adjuvant Therapy, Cytokine Therapy, Immunologic Testing
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants
- Lead sponsor
- Northern California Melanoma CenterUniversity, hospital or other
- Collaborators
- Bayer, Melanoma Research Institute
- Study start
- Sep 2004
- Study completion
- Jul 2010
- First posted
- 11 Jul 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a pilot study to describe the immunological responses and clinical outcome associated with administration of recombinant human Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) as surgical adjuvant therapy in patients with malignant melanoma who are at high risk for recurrence (Stage II T4, III and IV).
Detailed description
This is a pilot study to describe the immunological responses and clinical outcome associated with administration of recombinant human Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) as surgical adjuvant therapy in patients with malignant melanoma who are at high risk for recurrence (Stage II T4, III and IV). The immunological responses include serum neopterin levels. In a sub-set of study participants, additional immunologic testing will be done, including monocyte cytotoxicity to a melanoma cell line and phenotypic and functional markers of dendritic and T cell activation in peripheral blood mononuclear cells. The clinical end points of the study include safety, time to disease recurrence, time to disseminated disease, and survival. Eligible patients are those with high-risk melanoma who are clinically tumor free following surgery. Treatment will consist of GM-CSF at 125 g/m2 once daily (maximum dose 250 g) for 14 days followed by 14 days of rest (28 day cycle) for 1 year. Clinical status will be monitored until death or until the patient has been tumor free for five years, whichever event occurs first. Immunologic responses will be determined pretreatment, at the end of the first 14 days of dosing (Day 15), after the 14-day rest period (Day 29) and at the end of 14 days of dosing in cycles 6 (Day 155) and 13 (Day 351). Clinical outcome will be determined according to patient risk group (ultra-high risk Stage IIIC or IV versus high-risk Stage II T4, Stage IIIA and Stage IIIB). The pilot study will also assess the association of the immunological responses with clinical response and safety by patient risk group.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 14 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Eligible patients will be males or females with histologically proven melanoma. Patients must have Stage II (T4), III, and IV malignant melanoma surgically resected with no clinical evidence of disease by clinical, laboratory criteria or radiologic examination as defined below.
- Individuals must be at least 14 years of age.
- Pregnant women are not eligible. Men and women will be required to use an effective form of contraception.
- Patients requiring corticosteroid therapy or are receiving other forms of immunotherapy are not eligible.
- Patients may have received immunotherapy for prior disease. They must have completed therapy at least one month prior to study entry. Patients may not have received prior chemotherapy or therapy with GM-CSF. Patients are permitted to receive adjuvant radiation therapy but these patients will not be selected as part of the sub-set undergoing studies of cellular immunologic responses since the radiation could alter these responses. Based on the reults from one randomized, controlled clinical trial, the LEUKINE product labeling contains the following contraindication: "Due to the potential sensitivity of rapidly dividing hematopoietic progenitor cells, LEUKINE should not be administered simultaneously with cytoxic chemotherapy or radiotherapy or within 24 hours preceding or following chemotherapy or radiotherapy. In one controlled study, patients with small cell lung cancer received LEUKINE and concurrent thoracic radiotherapy and chemotherapy or the identical radiotherapy and chemotherapy without LEUKINE. The patients randomized to LEUKINE had significantly higher incidence of adverse events, including higher mortality and a higher incidence of grade 4 infections and grade 3 or 4 thrombocytopenia.28" Other investigators have reported that CM-CSF can be given safely with concurrent radiation therapy. These contrasting results may be related to differences in the patient populations or intensity and/or location of the site of radiotherapy in the body, among other factors. GM-CSF has been administered safely in combination with radiation therapy for treatment of head and neck cancers29,30 and has been used safely during regimens that combine chemotherapy and radiation therapy.31
Key exclusion criteria (1 listed)
- Patients not meeting Inclusion Criteria described above
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) | Drug | – |
Primary outcome
1 To describe the effect of GM-CSF adjuvant treatment of 125 ug/m2 once daily for 14 days followed by 14 days rest on immunological function as determined by serum neopterin levels (a measure of macrophage activation) and on serum levels of S100B.
5 secondary outcomes
To evaluate if a change of any or all of the immunological parameters over the treatment period is associated with safety and/or clinical outcome as measured by time to disease recurrence, time to disseminated disease and/or survival.
To perform a more detailed immunologic analysis in a sub-set of study participants (6 evaluable patients) to determine the immunologic responses induced by GM-CSF. There are three main immunological analyses to be determined:
a Monocyte cell numbers and activity
b Mature dendritic cell numbers
c Surface markers on peripheral blood mononuclear cells (PBMC) relative to T cells
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2006.
- Background: PubMed 10764421Spitler LE, Grossbard ML, Ernstoff MS, Silver G, Jacobs M, Hayes FA, Soong SJ. Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor. J Clin Oncol. 2000 Apr;18(8):1614-21. doi: 10.1200/JCO.2000.18.8.1614.
- Northern California Melanoma Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lynn E. Spitler, MD principal investigator
Northern California Melanoma Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in people with Malignant Melanoma, run by Northern California Melanoma Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jul 2006. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1 To describe the effect of GM-CSF adjuvant treatment of 125 ug/m2 once daily for 14 days followed by 14 days rest on immunological function as determined by serum neopterin levels (a measure of macrophage activation) and on serum levels of S100B.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00350597, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2006.