MelanomaPhase 2NCT00961376
Vaccination of Melanoma Patients With Total or CD25-depleted Peripheral Blood Mononuclear Cell (PBMC)
A Phase 2 study testing PBMC re-infusion and CD25 depletion in people with Melanoma, run by Providence Health & Services at 1 site in United States.
Trial summary
The objective of this study is to evaluate the safety and immunologic effects of autologous tumor vaccination administered with human granulocyte-macrophage colony-simulating factor (hGM-CSF), and subsequent boosting vaccinations in patients made lymphopenic by treatment with chemotherapy and infused with autologous… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- PBMC re-infusion and CD25 depletion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2009to 10 Feb 2015
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically confirmed malignant melanoma that is unresectable stage III or stage IV. Measurable disease is not required.
- Patients must have failed, refused, or not been eligible to receive at least one standard therapy regimen for metastatic disease.
- Easily harvested metastatic tumor cells e.g., skin or lymph node metastases or a planned surgery to remove tumor. Patients undergoing resection of a solitary brain metastasis are eligible if their resected lesion contains an adequate number of tumor cells. A minimum 2 cm x 2 cm x 2 cm lesion will be required for study eligibility.
- Sufficient viable tumor cells harvested to generate the vaccine. The tumor collected must contain greater than 1.6 x 108 viable tumor cells or a cell line generated from autologous tumor must provide greater than 1.6 x 108 viable tumor cells.
- Patients may have received prior chemotherapy and/or immunotherapy. Prior radiation therapy is acceptable but previously radiated sites may not be used for tumor collection for vaccine preparation.
- Life expectancy of greater than or = 3 months.
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- ECOG performance status <2 (Karnofsky >60%; see Appendix A).
- Patients must have normal organ and marrow function at the time of enrollment as defined in the protocol.
- Patients must be seronegative for HIV, Hepatitis B surface antigen and Hepatitis C antibody.
- If patients have had recent surgery, they must have recovered from the effects of that surgery in the opinion of the investigator.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients who have had chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C).
- Radiation therapy within 2 weeks. Prior radiation must have been to less 30% of the bone marrow and patient has recovered from all side effects, in the opinion of the investigator.
- Patients may not be receiving any other investigational agents.
- Steroid therapy, other than replacement steroids and inhaled steroids. Patients who might require systemic corticosteroids other than replacement steroids during the next three months are not eligible for this study.
- Patients with known brain metastases unless treated with radiation therapy and/or surgery and shown to be stable > 1 month.
- Autoimmune disease requiring treatment, with the exception of controlled autoimmune thyroiditis or vitiligo.
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- Pregnant or nursing women are excluded from this study because fludarabine and cyclophosphamide have potential teratogenic effects. It is not known whether fludarabine is excreted in breast milk but the package insert cautions that it might and recommends against breastfeeding if the mother is treated with fludarabine.
- Uncontrolled intercurrent illness which, in the opinion of the investigator, may increase the risks associated with study participation or interfere with the interpretation of the results..
- Any other medical illness or psychiatric condition/social situations that in the opinion of the principal investigator would compromise the patients ability to tolerate this treatment or would limit compliance with study requirements.
Trial locations and contacts
1 site in 1 country.
United States1 site
Providence Portland Medical Center
Portland, Oregon, 97213
About this study
Official title: Vaccination of Chemotherapy Induced Lymphopenic Unresectable Stage III or Stage IV Melanoma Patients Following Reconstitution With Total or CD25-depleted PBMC
The objective of this study is to evaluate the safety and immunologic effects of autologous tumor vaccination administered with human granulocyte-macrophage colony-simulating factor (hGM-CSF), and subsequent boosting vaccinations in patients made lymphopenic by treatment with chemotherapy and infused with autologous PBMC (Cohort A) or CD25 depleted PBMC (Cohort B). Clinical observations and laboratory measurements will be monitored to evaluate safety, toxicity, immune responses, and anti-tumor effects. Additionally, the effects of treatment on tumor response will be evaluated.
Read the detailed description
This is an open-label, outpatient Phase II, prospective, randomized, single-center, clinical trial. Up to 14 patients with a diagnosis of unresectable stage III or stage IV melanoma.
All patients will undergo leukapheresis to collect PBMC.
All patients will receive Cyclophosphamide 350 mg/m2 dl-3 and Fludarabine 20 mg/m2 dl-3.
Following chemotherapy to induce lymphopenia, patients will be re-infused with PDMC as follows:
Autologous PBMC re-infusion (Cohort A) Autologous, CD25-depleted PBMC re-infusion (Cohort B)
Following PBMC re-infusion, all patients will receive subcutaneous GM-CSF Infusion (50 micrograms/24 hrs) continuously for 6 days.
All patients will then receive 4 booster vaccinations as follows:
Intradermal injection of autologous tumor cells in the lower abdomen to deliver a total dose of at least 2x107 cells administered week 3, week 5, week 9 and week 13. Subcutaneous GM-CSF Infusion (50 micrograms/24 hrs) adjacent to the vaccine site begins at time of vaccination (week 3, 5, 9 and 13) and continues for 6 days.
- Conditions
- Melanoma
- Being tested
- PBMC re-infusion, CD25 depletion
- Keywords
- melanoma, unresectable stage III or IV melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PBMC re-infusionBiological
Autologous PBMC re-infusion
CD25 depletionBiological
Autologous, CD25-depleted PBMC re-infusion
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Active comparator | PBMC re-infusion Receives: Biological: PBMC re-infusion |
| Cohort B | Experimental | CD25 depletion Receives: Biological: CD25 depletion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immunologic effects (changes in the number of tumor specific T cells)
The absolute number and frequency of tumor specific T cells will be measured at days 7, 21, 35, 64, 91, and day 119.
Measured: Up to day 119
Secondary outcomes (1)
The number and severity of adverse events
Adverse events will be assessed on Days 7, 21, 35, 64, 91, and 119. Of special interest will be any adverse events thought to represent an autoimmune reaction.
Measured: Up to day 119
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2009 (estimated)
- Study startJul 2009
- Primary completionJan 2015
- Study completion10 Feb 2015
Why it stopped: PI Discretion
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Providence Health & Services
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Brendan Curti, MD, Principal investigator, Providence Health & Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00961376
- Sponsor's protocol ID
- PHS IRB 06-55
- Status last verified
- Aug 2018
- First submitted
- 14 Aug 2009
- Last updated
- 28 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vaccination of Chemotherapy Induced Lymphopenic Unresectable Stage III or Stage IV Melanoma Patients Following Reconstitution With Total or CD25-depleted PBMC
- ClinicalTrials.gov ID
- NCT00961376
- Acronym / sponsor ID
- PHS IRB 06-55
- Conditions
- Melanoma
- Keywords
- melanoma, unresectable stage III or IV melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI Discretion
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Providence Health & ServicesUniversity, hospital or other
- Study start
- Jul 2009 (actual)
- Primary completion
- Jan 2015 (actual)
- Study completion
- 10 Feb 2015 (actual)
- First posted
- 19 Aug 2009 (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.
The objective of this study is to evaluate the safety and immunologic effects of autologous tumor vaccination administered with human granulocyte-macrophage colony-simulating factor (hGM-CSF), and subsequent boosting vaccinations in patients made lymphopenic by treatment with chemotherapy and infused with autologous PBMC (Cohort A) or CD25 depleted PBMC (Cohort B). Clinical observations and laboratory measurements will be monitored to evaluate safety, toxicity, immune responses, and anti-tumor effects. Additionally, the effects of treatment on tumor response will be evaluated.
Detailed description
This is an open-label, outpatient Phase II, prospective, randomized, single-center, clinical trial. Up to 14 patients with a diagnosis of unresectable stage III or stage IV melanoma.
All patients will undergo leukapheresis to collect PBMC.
All patients will receive Cyclophosphamide 350 mg/m2 dl-3 and Fludarabine 20 mg/m2 dl-3.
Following chemotherapy to induce lymphopenia, patients will be re-infused with PDMC as follows:
Autologous PBMC re-infusion (Cohort A) Autologous, CD25-depleted PBMC re-infusion (Cohort B)
Following PBMC re-infusion, all patients will receive subcutaneous GM-CSF Infusion (50 micrograms/24 hrs) continuously for 6 days.
All patients will then receive 4 booster vaccinations as follows:
Intradermal injection of autologous tumor cells in the lower abdomen to deliver a total dose of at least 2x107 cells administered week 3, week 5, week 9 and week 13. Subcutaneous GM-CSF Infusion (50 micrograms/24 hrs) adjacent to the vaccine site begins at time of vaccination (week 3, 5, 9 and 13) and continues for 6 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Active comparator | Biological: PBMC re-infusionPBMC re-infusion |
| Cohort B | Experimental | Biological: CD25 depletionCD25 depletion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients must have histologically or cytologically confirmed malignant melanoma that is unresectable stage III or stage IV. Measurable disease is not required.
- Patients must have failed, refused, or not been eligible to receive at least one standard therapy regimen for metastatic disease.
- Easily harvested metastatic tumor cells e.g., skin or lymph node metastases or a planned surgery to remove tumor. Patients undergoing resection of a solitary brain metastasis are eligible if their resected lesion contains an adequate number of tumor cells. A minimum 2 cm x 2 cm x 2 cm lesion will be required for study eligibility.
- Sufficient viable tumor cells harvested to generate the vaccine. The tumor collected must contain greater than 1.6 x 108 viable tumor cells or a cell line generated from autologous tumor must provide greater than 1.6 x 108 viable tumor cells.
- Patients may have received prior chemotherapy and/or immunotherapy. Prior radiation therapy is acceptable but previously radiated sites may not be used for tumor collection for vaccine preparation.
Key exclusion criteria (9 listed)
- Patients who have had chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C).
- Radiation therapy within 2 weeks. Prior radiation must have been to less 30% of the bone marrow and patient has recovered from all side effects, in the opinion of the investigator.
- Patients may not be receiving any other investigational agents.
- Steroid therapy, other than replacement steroids and inhaled steroids. Patients who might require systemic corticosteroids other than replacement steroids during the next three months are not eligible for this study.
- Patients with known brain metastases unless treated with radiation therapy and/or surgery and shown to be stable > 1 month.
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 |
|---|---|---|
| PBMC re-infusionAutologous PBMC re-infusion | Biological | Cohort A |
| CD25 depletionAutologous, CD25-depleted PBMC re-infusion | Biological | Cohort B |
Primary outcome
Immunologic effects (changes in the number of tumor specific T cells)
Time frame: Up to day 119
The absolute number and frequency of tumor specific T cells will be measured at days 7, 21, 35, 64, 91, and day 119.
1 secondary outcome
The number and severity of adverse events
Time frame: Up to day 119
Results and safety
The study was stopped early (reason given: PI Discretion). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2018.
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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.
Brendan Curti, MD principal investigator
Providence Health & Services
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 PBMC re-infusion and CD25 depletion in people with Melanoma, run by Providence Health & Services 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 11 inclusion and 9 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: stopped early, as of the sponsor's last update on 28 Aug 2018. 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 was stopped early (reason given: PI Discretion). Results are not available in the source record.
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?
Immunologic effects (changes in the number of tumor specific T cells) (time frame: Up to day 119). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Aug 2018.