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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03782363
Recruitment Status : Not yet recruiting
First Posted : December 20, 2018
Last Update Posted : February 17, 2020
Sponsor:
Collaborator:
Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna
Information provided by (Responsible Party):
Italian Sarcoma Group

Brief Summary:

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)


Condition or disease Intervention/treatment Phase
Sarcoma Biological: Autologous CIK Dose level 1 Biological: Autologous CIK Dose level 2 Biological: Autologous CIK Dose level 3 Biological: Autologous CIK Dose level 4 Phase 1

Detailed Description:

In the first part of the study the patient's' peripheral blood collected from and CIK cell expansion and storage at the Regina Margherita Children's Hospital Cell Factory.

Approximately 40 patients will be enrolled in part 1 (range: 30 - 50 patients). The second part of the study will be a 3+3 dose escalation design to determine the MTD/RP2D.

A Safety Monitoring Committee (SMC) will be appointed to make dose escalation decisions.

Approximately 30 patients will be enrolled in this part (range: 6 - 36 patients).

Only one infusion of autologous CIK cells will be carried out at each cycle, every 21 days at the 1st, 2nd and 3rd dose levels and every 15 days at the 4th, 5th 6th dose levels.

A maximum of 6 cycles will be performed (patient with complete disease remission patients who benefit from treatment might also receive more cycles at the Investigator's discretion)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose finding study for the determination of the MTD for the RP2D with cohort of 3 patients plus 3 other patients as scaling design
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Adoptive Immunotherapy With Cytokine-Induced Killer Cells in Relapsed and Non-resectable Sarcomas After Multimodal Treatment.
Estimated Study Start Date : April 1, 2020
Estimated Primary Completion Date : April 1, 2023
Estimated Study Completion Date : April 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Autologous CIK Dose level 1
autologous CIK at dose level 1
Biological: Autologous CIK Dose level 1
Lymphocytapheresis of the autologous ex-vivo CIK cell expanded in the Cell factory at first level of dose 20.000.000 cell/kgs days 1 and 22

Experimental: Autologous CIK Dose level 2
autologous CIK at dose level 2
Biological: Autologous CIK Dose level 2
Lymphocytapheresis of the autologous ex-vivo CIK cell expanded in the Cell factory at first level of dose 25.000.000 cell/kgs days 1 and 22

Experimental: Autologous CIK Dose level 3
autologous CIK at dose level 3
Biological: Autologous CIK Dose level 3
Lymphocytapheresis of the autologous ex-vivo CIK cell expanded in the Cell factory at first level of dose 20.000.000 cell/kgs days 1 and 15

Experimental: Autologous CIK Dose level 4
autologous CIK at dose level 4
Biological: Autologous CIK Dose level 4
Lymphocytapheresis of the autologous ex-vivo CIK cell expanded in the Cell factory at first level of dose 25.000.000 cell/kgs days 1 and 15




Primary Outcome Measures :
  1. Incidence of dose-limiting toxicity (DLT) associated with CIK autologous cells administration [ Time Frame: at week 6 ]

    The MTD will be determined through dose-escalation using a 3+3 cohort design. If less than oner third of evaluable patients in a given cohort (0 of 3 patients or 1 of 6 patients) experiences a DLT; escalation may proceed to the next higher dose level.

    If one of the first 3 patients enrolled in a given cohort experiences a DLT, at least 3 additional patents will be enrolled in that cohort.

    If a DLT is observed in one-third or more of patients, the dose at which this occurs will be considered not tolerated and the MTD will have been exceeded. The highest dose level(s) at which less than one-third of patients (0 of 3 patients or 1 of 6 patients) experiences a DLT will be declared the MTD and will be used as RP2D



Secondary Outcome Measures :
  1. Plasma concentration of autologous CIK cells for pharmacokinetic [ Time Frame: At every cycle up to cycle 6 at: a) day 1 pre-dose b) 4 hours post-infusion, c) 24 hours post-infusion, d) day8 , e) day 15 ]
    Evaluation of the plasma concentration of autologous CIK cells to determine the pharmacokinetics parameter of the autologous CIK cells

  2. Progression free Survival [ Time Frame: At month 4 ]
    Survival free of disease progression

  3. Evaluation of Major histocompatibility complex class I-related chains A and B on tumor material [ Time Frame: pre-dose ]
    Major histocompatibility complex class I-related chains A and B expression in the tumor

  4. Evaluation of UL16 binding proteins on tumor material [ Time Frame: pre-dose ]
    UL16 binding proteins expression in the tumor

  5. Quality of live reported by the Patients Using European Organisation of Research and Treatment (EORTC) Quality of Life Questionnaire Questionnaire-Core 30 (QLQ-C30) [ Time Frame: at week 6 ]
    Evaluation of the quality of life during treatment



Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for part 1

  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;
  2. Karnofsky score ≥ 70% (patients with Karnofsky score ≥ 50% are eligible if it depends solely on orthopedic problems)
  3. Estimated life expectancy > 3 months;
  4. Adequate bone marrow functions:
  5. Signed informed consent;
  6. Negative serum or urine pregnancy test within 48 hours from collection of peripheral blood or from lympho cyto apheresis (if post-pubertal female patients);
  7. Archived histological tumour sample available

Inclusion Criteria for part 2

  1. Patients with histologically documented unresectable sarcomas which progressed after a first or further line treatments for relapsing disease
  2. Measurable disease (bone lesions are included);
  3. Karnofsky score ≥ 70% (patients with Karnofsky score ≥ 50% are eligible if its depend solely on orthopedic problems)
  4. Estimated life expectancy > 3 months;
  5. Adequate bone marrow, hepatic and renal functionality
  6. Signed informed consent;
  7. Archived histological tumour sample available;
  8. Patients should have a venous central access;
  9. 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

  1. History of Human Immunodeficiency Virus, Hepatitis C Virus, Hepatitis B Virus or Hepatitis A Virus infection;
  2. 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;
  3. 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

  1. Patients with Ewing/Primitive Neuroectodermal Tumor Sarcoma, Rhabdomyosarcoma as well as other rapidly growing sarcomas are not to be included in the study;
  2. Presence of Central Nervous System metastases and/or meningeal neoplastic involvement;
  3. Patients with seizure disorders;
  4. Severe renal, vascular, cardiac, hepatic, lung disorders;
  5. 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
  6. Patients with a non-optimal ex-vivo expansion of autologous CIK cells during Part 1 (< 0.5 x 107/kg CIK cells);
  7. History of Human Immunodeficiency Virus, Hepatitis C Virus, Hepatitis B Virus or Hepatitis A Virus infection;
  8. Presence of bleeding disorders;
  9. Patients undergoing renal dialysis;
  10. Presence of uncontrolled diabetes
  11. Patients unable to swallow oral medications;
  12. Patients receiving concomitant steroid or immunotherapy (except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg for adrenal insufficiency).
  13. Anticancer chemotherapy or experimental drugs or immunotherapy or radiotherapy 2 weeks before entering the study;
  14. Anticancer chemotherapy or experimental drugs or immunotherapy or radiotherapy on target lesions 2 weeks before entering the study;
  15. Prior exposure to CIK cells;
  16. Major surgery 4 weeks before entering the study;
  17. Minor surgery 1 week before entering the study;
  18. Patients with allergic reactions or hypersensibility to excipient
  19. Pregnant or breast-feeding patients;
  20. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03782363


Contacts
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Contact: Franca Faggioli, MD 0039011313 ext 5447 franca.fagioli@unito.it
Contact: Elisa Tirtei, MD 0039011313 ext 5447 elisa.tirtei@gmail.com

Locations
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Italy
Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology
Torino, Italy, 10126
Sponsors and Collaborators
Italian Sarcoma Group
Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna
Investigators
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Principal Investigator: Franca Faggioli, MD Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology

Publications:

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Responsible Party: Italian Sarcoma Group
ClinicalTrials.gov Identifier: NCT03782363    
Other Study ID Numbers: ISG-CAST
First Posted: December 20, 2018    Key Record Dates
Last Update Posted: February 17, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Italian Sarcoma Group:
advanced sarcoma
osteosarcoma
soft tissue sarcoma
Additional relevant MeSH terms:
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Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms