Clinical trial NCT01988077: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: A Combination of Adoptive T Cell Therapy and Ipilimumab Could Increase the Proportion of CR Patients, and Durability of Response
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2013-11-20
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
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.
timeFrame: October 2017
Secondary outcomes:
measure: • Evaluate the toxicity of this treatment regimen.
timeFrame: Follow up for 1 year
Other outcomes:
measure: Determine duration of response
timeFrame: follow up for 1 year
measure: Determine overall survival
timeFrame: follow up for 1 year
Locations:
city: Ramat Gan
country: Israel
facility: Sheba. Medical Center
Study officials:
affiliation: Sheba Medical Center
name: Jacob Schachter, Prof.
role: PRINCIPAL_INVESTIGATOR
References: