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SarcomaPhase 1CASTNCT03782363

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

A Phase 1 study testing Autologous CIK Dose level 1, Autologous CIK Dose level 2 and Autologous CIK Dose level 3 in people with Sarcoma, run by Italian Sarcoma Group at 1 site in Italy.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 10 years and older
Conditions the study is for
Sarcoma
What is being tested?
Autologous CIK Dose level 1, Autologous CIK Dose level 2 and Autologous CIK Dose level 3
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteItaly
Study dates
18 Dec 2020to 1 Apr 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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);
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  • Archived histological tumour sample available
  • 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.

Who cannot join

  • 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.
  • 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;
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  • 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.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Ospedale Infantile Regina Margherita - Unit of Paediatric Oncoematology

    Torino, 10126

Other trials in Italy

About this study

Official title: 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)

Read the 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)

Conditions
Sarcoma
Being tested
Autologous CIK Dose level 1, Autologous CIK Dose level 2, Autologous CIK Dose level 3, Autologous CIK Dose level 4
Keywords
advanced sarcoma, osteosarcoma, soft tissue sarcoma
Medical subject headings
Sarcoma, Osteosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous CIK Dose level 1Biological

    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

  • Autologous CIK Dose level 2Biological

    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

  • Autologous CIK Dose level 3Biological

    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

  • Autologous CIK Dose level 4Biological

    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

Study groups in NCT03782363
Study groupRoleWhat they receive
Autologous CIK Dose level 1Experimentalautologous CIK at dose level 1
Receives: Biological: Autologous CIK Dose level 1
Autologous CIK Dose level 2Experimentalautologous CIK at dose level 2
Receives: Biological: Autologous CIK Dose level 2
Autologous CIK Dose level 3Experimentalautologous CIK at dose level 3
Receives: Biological: Autologous CIK Dose level 3
Autologous CIK Dose level 4Experimentalautologous CIK at dose level 4
Receives: Biological: Autologous CIK Dose level 4

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose-limiting toxicity (DLT) associated with CIK autologous cells administration

    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

    Measured: at week 6

Secondary outcomes (5)

  1. Plasma concentration of autologous CIK cells for pharmacokinetic

    Evaluation of the plasma concentration of autologous CIK cells to determine the pharmacokinetics parameter of the autologous CIK cells

    Measured: 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

  2. Progression free Survival

    Survival free of disease progression

    Measured: At month 4

  3. Evaluation of Major histocompatibility complex class I-related chains A and B on tumor material

    Major histocompatibility complex class I-related chains A and B expression in the tumor

    Measured: pre-dose

  4. Evaluation of UL16 binding proteins on tumor material

    UL16 binding proteins expression in the tumor

    Measured: pre-dose

  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)

    Evaluation of the quality of life during treatment

    Measured: at week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Dec 2018
  2. Study start18 Dec 2020
  3. Primary completion1 Apr 2023 (estimated)
  4. Study completion1 Apr 2023 (estimated)

Why it stopped: Initial version of the protocol not submitted and new version approved has a new sponsor and it has been added into Clinicaltrials by the new sponsor

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
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)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03782363
Sponsor's protocol ID
ISG-CAST
Acronym
CAST
Status last verified
Dec 2020
First submitted
17 Dec 2018
Last updated
22 Dec 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Schmidt-Wolf IG, Lefterova P, Mehta BA, Fernandez LP, Huhn D, Blume KG, Weissman IL, Negrin RS. Phenotypic characterization and identification of effector cells involved in tumor cell recognition of cytokine-induced killer cells. Exp Hematol. 1993 Dec;21(13):1673-9.

    PubMed 7694868

  • Introna M, Franceschetti M, Ciocca A, Borleri G, Conti E, Golay J, Rambaldi A. Rapid and massive expansion of cord blood-derived cytokine-induced killer cells: an innovative proposal for the treatment of leukemia relapse after cord blood transplantation. Bone Marrow Transplant. 2006 Nov;38(9):621-7. doi: 10.1038/sj.bmt.1705503. Epub 2006 Sep 18.

    PubMed 16980990

  • Mesiano G, Todorovic M, Gammaitoni L, Leuci V, Giraudo Diego L, Carnevale-Schianca F, Fagioli F, Piacibello W, Aglietta M, Sangiolo D. Cytokine-induced killer (CIK) cells as feasible and effective adoptive immunotherapy for the treatment of solid tumors. Expert Opin Biol Ther. 2012 Jun;12(6):673-84. doi: 10.1517/14712598.2012.675323. Epub 2012 Apr 14.

    PubMed 22500889

  • Olioso P, Giancola R, Di Riti M, Contento A, Accorsi P, Iacone A. Immunotherapy with cytokine induced killer cells in solid and hematopoietic tumours: a pilot clinical trial. Hematol Oncol. 2009 Sep;27(3):130-9. doi: 10.1002/hon.886.

    PubMed 19294626

  • Heimann TG, Githens S. Rat pancreatic duct epithelium cultured on a porous support coated with extracellular matrix. Pancreas. 1991 Sep;6(5):514-21. doi: 10.1097/00006676-199109000-00003.

    PubMed 1946307

  • Gammaitoni L, Giraudo L, Macagno M, Leuci V, Mesiano G, Rotolo R, Sassi F, Sanlorenzo M, Zaccagna A, Pisacane A, Senetta R, Cangemi M, Cattaneo G, Martin V, Coha V, Gallo S, Pignochino Y, Sapino A, Grignani G, Carnevale-Schianca F, Aglietta M, Sangiolo D. Cytokine-Induced Killer Cells Kill Chemo-surviving Melanoma Cancer Stem Cells. Clin Cancer Res. 2017 May 1;23(9):2277-2288. doi: 10.1158/1078-0432.CCR-16-1524. Epub 2016 Nov 4.

    PubMed 27815354

  • Chan JK, Hamilton CA, Cheung MK, Karimi M, Baker J, Gall JM, Schulz S, Thorne SH, Teng NN, Contag CH, Lum LG, Negrin RS. Enhanced killing of primary ovarian cancer by retargeting autologous cytokine-induced killer cells with bispecific antibodies: a preclinical study. Clin Cancer Res. 2006 Mar 15;12(6):1859-67. doi: 10.1158/1078-0432.CCR-05-2019.

    PubMed 16551871

  • Kim HM, Lim J, Yoon YD, Ahn JM, Kang JS, Lee K, Park SK, Jeong YJ, Kim JM, Han G, Yang KH, Kim YJ, Kim Y, Han SB. Anti-tumor activity of ex vivo expanded cytokine-induced killer cells against human hepatocellular carcinoma. Int Immunopharmacol. 2007 Dec 15;7(13):1793-801. doi: 10.1016/j.intimp.2007.08.007. Epub 2007 Aug 31.

    PubMed 17996690

  • Schmidt-Wolf IG, Finke S, Trojaneck B, Denkena A, Lefterova P, Schwella N, Heuft HG, Prange G, Korte M, Takeya M, Dorbic T, Neubauer A, Wittig B, Huhn D. Phase I clinical study applying autologous immunological effector cells transfected with the interleukin-2 gene in patients with metastatic renal cancer, colorectal cancer and lymphoma. Br J Cancer. 1999 Nov;81(6):1009-16. doi: 10.1038/sj.bjc.6690800.

    PubMed 10576658

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Autologous CIK Dose level 1, Autologous CIK Dose level 2 and Autologous CIK Dose level 3 in people with Sarcoma, run by Italian Sarcoma Group at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 22 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose-limiting toxicity (DLT) associated with CIK autologous cells administration (time frame: at week 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03782363, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2020.

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