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

December 18, 2020 updated by: Italian Sarcoma Group

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

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)

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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)

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Torino, Italy, 10126
        • Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
at week 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
Progression free Survival
Time Frame: At month 4
Survival free of disease progression
At month 4
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
pre-dose
Evaluation of UL16 binding proteins on tumor material
Time Frame: pre-dose
UL16 binding proteins expression in the tumor
pre-dose
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
at week 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Italian Sarcoma Group

Collaborators

Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna

Investigators

  • Principal Investigator: Franca Faggioli, MD, Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 18, 2020

Primary Completion (Anticipated)

April 1, 2023

Study Completion (Anticipated)

April 1, 2023

Study Registration Dates

First Submitted

December 17, 2018

First Submitted That Met QC Criteria

December 18, 2018

First Posted (Actual)

December 20, 2018

Study Record Updates

Last Update Posted (Actual)

December 22, 2020

Last Update Submitted That Met QC Criteria

December 18, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISG-CAST

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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