Clinical Evaluation of Yervoy in Combination With Adoptive T Cell Transfer for Metastatic Melanoma Patients
Primary Purpose
A Combination of Adoptive T Cell Therapy and Ipilimumab Could Increase the Proportion of CR Patients, and Durability of Response
Status
Terminated
Phase
Phase 2
Locations
Israel
Study Type
Interventional
Intervention
Adoptive cell transfer
Ipilimumab 5 MG/ML Injection [Yervoy]
Sponsored by

About this trial
This is an interventional treatment trial for A Combination of Adoptive T Cell Therapy and Ipilimumab Could Increase the Proportion of CR Patients, and Durability of Response
Eligibility Criteria
Inclusion Criteria:
- 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:
- 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.
Exclusion Criteria:
- 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:
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
Sites / Locations
- Sheba. Medical Center
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Adoptive cell transfer combined with Ipilimumab
Arm Description
Adoptive cell transfer combined with Ipilimumab
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
• 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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01988077
Brief Title
Clinical Evaluation of Yervoy in Combination With Adoptive T Cell Transfer for Metastatic Melanoma Patients
Official Title
Clinical Evaluation of Yervoy in Combination With Adoptive T Cell Transfer for the Treatment of Metastatic Melanoma Patients
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Terminated
Why Stopped
due to toxicity of cyclophosphamide
Study Start Date
October 2013 (undefined)
Primary Completion Date
May 20, 2016 (Actual)
Study Completion Date
October 25, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sheba Medical Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
A Combination of Adoptive T Cell Therapy and Ipilimumab Could Increase the Proportion of CR Patients, and Durability of Response
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Adoptive cell transfer combined with Ipilimumab
Arm Type
Other
Arm Description
Adoptive cell transfer combined with Ipilimumab
Intervention Type
Biological
Intervention Name(s)
Adoptive cell transfer
Intervention Description
Adoptive cell transfer
Intervention Type
Drug
Intervention Name(s)
Ipilimumab 5 MG/ML Injection [Yervoy]
Intervention Description
2 treatments of Ipilimumab before transfer of TIL and 2 treatments of Ipilimumab after TIL
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
• Evaluate the toxicity of this treatment regimen.
Description
Toxicity will be reported by type and severity according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.
Time Frame
Follow up for 1 year
Other Pre-specified Outcome Measures:
Title
Determine duration of response
Time Frame
follow up for 1 year
Title
Determine overall survival
Time Frame
follow up for 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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:
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.
Exclusion Criteria:
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:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacob Schachter, Prof.
Organizational Affiliation
Sheba Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sheba. Medical Center
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
to be decided
Learn more about this trial
Clinical Evaluation of Yervoy in Combination With Adoptive T Cell Transfer for Metastatic Melanoma Patients
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