Study of Adoptive Immunotherapy in Relapsed and Non-resectable Sarcomas After Multimodal Treatment.

Study Overview
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Brief Summary
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Monocentric, phase I study for advanced sarcoma with adoptive immunotherapy with Cytokine-Induced Killer (CIK). In the first part of the study Patient's' peripheral blood will be collected and CIK cell expansion and storage will occur at the Regina Margherita Children's Hospital Cell Factory. In the second part of the study the Maximum Tolerated Dose (MTD) will be determined in order to find the Recommended Dose for Phase II (RP2D)

Official Title
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A Phase I Study of Adoptive Immunotherapy With Cytokine-Induced Killer Cells in Relapsed and Non-resectable Sarcomas After Multimodal Treatment.

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: Autologous CIK


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for part 1 Patients with histologically documented unresectable sarcomas which progressed after first or further line treatments for relapsing disease who could be enrolled in Part 2 of study immediately or after a new line of treatment; Karnofsky score ≥ 70% (patients with Karnofsky score ≥ 50% are eligible if it depends solely on orthopedic problems) Estimated life expectancy > 3 months; Adequate bone marrow functions: Signed informed consent; Negative serum or urine pregnancy test within 48 hours from collection of peripheral blood or from lympho cyto apheresis (if post-pubertal female patients); Archived histological tumour sample available Inclusion Criteria for part 2 Patients with histologically documented unresectable sarcomas which progressed after a first or further line treatments for relapsing disease Measurable disease (bone lesions are included); Karnofsky score ≥ 70% (patients with Karnofsky score ≥ 50% are eligible if its depend solely on orthopedic problems) Estimated life expectancy > 3 months; Adequate bone marrow, hepatic and renal functionality Signed informed consent; Archived histological tumour sample available; Patients should have a venous central access; Pregnancy test should be negative 48 hours before treatment for post-pubertal women patients. All post-pubertal patients are to take adequate anti-contraceptive measures during treatment and until 8 weeks after the last dose of treatment. Exclusion Criteria for part 1 History of Human Immunodeficiency Virus, Hepatitis C Virus, Hepatitis B Virus or Hepatitis A Virus infection; Patients receiving chemotherapy and/or immunotherapy and/or anti-tumour agents and/or radiotherapy on more than 10% of bone marrow area two weeks before peripheral blood collection or lymphocytapheresis; Patients with neuro-psychiatric disorders or social or geographic problems that would prohibit the understanding or rendering informed consent and compliance with the requirements of this protocol are excluded. Exclusion Criteria for part 2 Patients with Ewing/Primitive Neuroectodermal Tumor Sarcoma, Rhabdomyosarcoma as well as other rapidly growing sarcomas are not to be included in the study; Presence of Central Nervous System metastases and/or meningeal neoplastic involvement; Patients with seizure disorders; Severe renal, vascular, cardiac, hepatic, lung disorders; Patients with any severe and/or uncontrolled medical conditions such as unstable angina pectoris, heart failure ≥ grade 2, a recent heart attack within 6 months, uncontrolled heart non arrhythmia uncontrolled metabolic disorders, cirrhosis, uncontrolled hypertension Patients with a non-optimal ex-vivo expansion of autologous CIK cells during Part 1 (< 0.5 x 107/kg CIK cells); History of Human Immunodeficiency Virus, Hepatitis C Virus, Hepatitis B Virus or Hepatitis A Virus infection; Presence of bleeding disorders; Patients undergoing renal dialysis; Presence of uncontrolled diabetes Patients unable to swallow oral medications; Patients receiving concomitant steroid or immunotherapy (except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg for adrenal insufficiency). Anticancer chemotherapy or experimental drugs or immunotherapy or radiotherapy 2 weeks before entering the study; Anticancer chemotherapy or experimental drugs or immunotherapy or radiotherapy on target lesions 2 weeks before entering the study; Prior exposure to CIK cells; Major surgery 4 weeks before entering the study; Minor surgery 1 week before entering the study; Patients with allergic reactions or hypersensibility to excipient Pregnant or breast-feeding patients; Patients with neuro-psychiatric disorders or social or geographic problems that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol are excluded.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CIK<br> | Drug: Autologous CIK<br>* Lymphocytapheresis of the autologous ex-vivo CIK cell expanded in the Cell factory (4 dose levels)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT | Incidence of dose-limiting toxicity (DLT) associated with CIK autologous cells administration | 6 weeks |