A Combination of Adoptive T Cell Therapy and Ipilimumab Could Increase the Proportion of CR Patients, and Durability of ResponsePhase 2NCT01988077
Clinical Evaluation of Yervoy in Combination With Adoptive T Cell Transfer for Metastatic Melanoma Patients
A Phase 2 study testing Adoptive cell transfer and Ipilimumab 5 MG/ML Injection [Yervoy] in people with A Combination of Adoptive T Cell Therapy and Ipilimumab Could Increase the Proportion of CR Patients, and Durability of Response, run by Sheba Medical Center at 1 site in Israel.
Trial summary
A rationally designed combination of adoptive T cell therapy and ipilimumab could strongly increase the proportion of CR patients, as well as the durability of response, as compared to ipilimumab or TIL alone. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- A Combination of Adoptive T Cell Therapy and Ipilimumab Could Increase the Proportion of CR Patients, and Durability of Response
- What is being tested?
- Adoptive cell transfer and Ipilimumab 5 MG/ML Injection [Yervoy]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteIsrael
- Study dates
- Oct 2013to 25 Oct 2018
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women, ≥ 18 years of age.
- Measurable metastatic melanoma (defined histologically) with at least one lesion that is resectable for TIL generation:
- Patients with asymptomatic brain metastases are allowed
- Previously treated or untreated unresectable stage III or stage IV melanoma
- Clinical performance status of ECOG 0 or 1.
- Laboratory:
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- ANC ≥ than 1000 k/microL without support of filgrastim
- WBC > 3000 k/microL
- Hemoglobin greater than 8.0 g/dL
- Platelet count greater than 100,000 K/microL
- Seronegative for HIV, HBV, HCV
- Serum ALT/AST less than three times the upper limit of normal.
- Serum creatinine less than or equal to 1.6 mg/dL.
- Total bilirubin less than or equal to 2 mg/dL, except in patients with Gilbert's syndrome who must have a total bilirubin less than 3 mg/dl.
- An interval of at least 28 days since last oncological treatment to the first ipilimumab course. Palliative radiation therapy outside of the brain or therapeutic radiation to the brain after the patient's condition is stabilized and systemic steroids required for the management of systems due to brain metastases is decreased to the lowest fixed dose possible does not require 28-day waiting period.
- Negative pregnancy test in women of child bearing potentialwithin 72 hours before the start of ipilimumab.
- Willing to practice effective birth control during treatment and for 26 weeks after receiving the last dose of ipilimumab (both women of child bearing potential and men of fathering potential).
- Life expectancy greater than three months.
Who cannot join
- Failure to meet all of the inclusion criteria.
- Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).
- Active concurrent malignant disease, or disease-free for less than 5 years (exception: adequately treated basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix)
- Patients receiving any non-oncology vaccine therapy used for prevention of infectious diseases for up to 4 weeks before or after any dose of ipilimumab with the exception of amantadine and flumadine, will not be eligible for ipilimumab treatment.
- Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
- Active systemic infections, coagulation disorders or other active major medical illnesses:
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- Cardiovascular:
- History of coronary revascularization or ischemic symptoms
- Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
- Left ventricular EF of 45% or less.
- Respiratory:
- Documented FEV1 less than or equal to 70% tested in patients with symptoms of respiratory dysfunction
- Immune system
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS)
- Hepatitis B and C infection, regardless of the control on antiviral therapy
- Opportunistic infections
- Any subject who has a life-threatening condition that requires high-dose immunosuppressant(s).
- A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA 4 inhibitor or agonist
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious) illness.
- Women of child-bearing potential:
- Pregnant, breastfeeding, or unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 8 weeks after cessation of study drug
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Evaluation of Yervoy in Combination With Adoptive T Cell Transfer for the Treatment of Metastatic Melanoma Patients
A rationally designed combination of adoptive T cell therapy and ipilimumab could strongly increase the proportion of CR patients, as well as the durability of response, as compared to ipilimumab or TIL alone. The investigators hypothesize that the combination of those two important modalities could result in a durable (≥ 1 year) complete response rate of 30% in stage IV melanoma patients.
- Being tested
- Adoptive cell transfer, Ipilimumab 5 MG/ML Injection [Yervoy]
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adoptive cell transferBiological
Adoptive cell transfer
Ipilimumab 5 MG/ML Injection [Yervoy]Drug
2 treatments of Ipilimumab before transfer of TIL and 2 treatments of Ipilimumab after TIL
| Study group | Role | What they receive |
|---|---|---|
| Adoptive cell transfer combined with Ipilimumab | Other | Adoptive cell transfer combined with Ipilimumab Receives: Biological: Adoptive cell transfer; Drug: Ipilimumab 5 MG/ML Injection [Yervoy] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the response rate of the combination of ipilimumab with young TIL protocol and the CR rate of this combination according to modified RECIST 1.1.
Measured: October 2017
Secondary outcomes (1)
• Evaluate the toxicity of this treatment regimen.
Toxicity will be reported by type and severity according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.
Measured: Follow up for 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2013 (estimated)
- Study startOct 2013
- Primary completion20 May 2016
- Study completion25 Oct 2018
Why it stopped: due to toxicity of cyclophosphamide
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for A Combination of Adoptive T Cell Therapy and Ipilimumab Could Increase the Proportion of CR Patients, and Durability of ResponseStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Dr. Jacob Schachter MD,, Sheba Medical Center
- Investigators
- Jacob Schachter, Prof., Principal investigator, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01988077
- Sponsor's protocol ID
- Ipilimumab TIL
- Status last verified
- Apr 2019
- First submitted
- 24 Oct 2013
- Last updated
- 5 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided: to be decided
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Evaluation of Yervoy in Combination With Adoptive T Cell Transfer for the Treatment of Metastatic Melanoma Patients
- ClinicalTrials.gov ID
- NCT01988077
- Acronym / sponsor ID
- Ipilimumab TIL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: due to toxicity of cyclophosphamide
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- Oct 2013
- Primary completion
- 20 May 2016 (actual)
- Study completion
- 25 Oct 2018 (actual)
- First posted
- 20 Nov 2013 (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.
A rationally designed combination of adoptive T cell therapy and ipilimumab could strongly increase the proportion of CR patients, as well as the durability of response, as compared to ipilimumab or TIL alone. The investigators hypothesize that the combination of those two important modalities could result in a durable (≥ 1 year) complete response rate of 30% in stage IV melanoma patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adoptive cell transfer combined with Ipilimumab | Other | Biological: Adoptive cell transfer, Drug: Ipilimumab 5 MG/ML Injection [Yervoy]Adoptive cell transfer combined with Ipilimumab |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Men and women, ≥ 18 years of age.
- Measurable metastatic melanoma (defined histologically) with at least one lesion that is resectable for TIL generation:
- Patients with asymptomatic brain metastases are allowed
- Previously treated or untreated unresectable stage III or stage IV melanoma
- Clinical performance status of ECOG 0 or 1.
Key exclusion criteria (22 listed)
- Failure to meet all of the inclusion criteria.
- Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).
- Active concurrent malignant disease, or disease-free for less than 5 years (exception: adequately treated basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix)
- Patients receiving any non-oncology vaccine therapy used for prevention of infectious diseases for up to 4 weeks before or after any dose of ipilimumab with the exception of amantadine and flumadine, will not be eligible for ipilimumab treatment.
- Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
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 |
|---|---|---|
| Adoptive cell transferAdoptive cell transfer | Biological | Adoptive cell transfer combined with Ipilimumab |
| Ipilimumab 5 MG/ML Injection [Yervoy]2 treatments of Ipilimumab before transfer of TIL and 2 treatments of Ipilimumab after TIL | Drug | Adoptive cell transfer combined with Ipilimumab |
Primary outcome
Determine the response rate of the combination of ipilimumab with young TIL protocol and the CR rate of this combination according to modified RECIST 1.1.
Time frame: October 2017
1 secondary outcome
• Evaluate the toxicity of this treatment regimen.
Time frame: Follow up for 1 year
Results and safety
The study was stopped early (reason given: due to toxicity of cyclophosphamide). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2019.
- Individual participant dataSharing planned: Undecided. to be decided
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.
Jacob Schachter, Prof. principal investigator
Sheba Medical 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 Adoptive cell transfer and Ipilimumab 5 MG/ML Injection [Yervoy] in people with A Combination of Adoptive T Cell Therapy and Ipilimumab Could Increase the Proportion of CR Patients, and Durability of Response, run by Sheba Medical Center at 1 site in Israel.
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 18 inclusion and 22 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 5 Apr 2019. 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 Israel. 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: due to toxicity of cyclophosphamide). 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?
Determine the response rate of the combination of ipilimumab with young TIL protocol and the CR rate of this combination according to modified RECIST 1.1. (time frame: October 2017). 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 5 Apr 2019.