NCT03412526

Brief Summary

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) in combination with lymphodepletion and high-dose interleukin 2. Most TIL ACT trials have been conducted as salvage therapy for patients who already had failed numerous treatments; many study participants presented with multiple metastases, frequently in visceral organs and even in the brain. The effectiveness of TIL ACT in eradicating metastatic tumors of the responding patients underlines the value of this immunotherapeutic approach. Recent developments in the identification and selection of tumor-specific T-cell populations have facilitated the implementation of TIL ACT also in nonmelanoma malignancies. Building on the experience of Ella Lemelbaum Institute, Sheba Medical Center with ACT TIL in the treatment of metastatic melanoma, the Dept. of Oncology, Tel HaShomer has expanded the use of TIL ACT following a reduced intensity, non-myeloablative, lymphodepleting induction regimen to metastatic Melanoma, Ovarian (OC) and Cervical cancer patients. The rationale supporting these studies is to further develop the ACT TIL procedure and expand its applicability to metastatic OC and cervical cancers.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
15

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jan 2018

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 21, 2018

Completed
Same day until next milestone

Study Start

First participant enrolled

January 21, 2018

Completed
5 days until next milestone

First Posted

Study publicly available on registry

January 26, 2018

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2021

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2022

Completed
Last Updated

April 4, 2019

Status Verified

April 1, 2019

Enrollment Period

3 years

First QC Date

January 21, 2018

Last Update Submit

April 3, 2019

Conditions

Metastatic Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

  • Objective Tumor responses

    Radiological follow up via CT to determine the sum of complete Responders (CR) + Partial Responders (PR) +Stable Disease (SD) as assessment by RECICT 1.1

    3 years

  • Assess adverse events using NCI CTCAE V.4.03 during treatment and follow up

    adverse events will be assess using MCI CTCAE V.4.03 during treatment and follow up

    3 years

Secondary Outcomes (4)

  • Overall survival (OS)

    3 years

  • Response Rate( RR)

    3 years

  • Progression Free Survival (PFS)

    3 years

  • Quality of Life (QoL)

    3 years

Study Arms (1)

ACT TIL

EXPERIMENTAL

1. Reduced Intensity, non-myeloablative, lymphodepleting induction regimen using Fludarabine (25 mg/m2 for 3 days) followed by Total Body Radiation (TBR) (2 Gray as a single treatment) for 1 day 2. Preparation and administration of unselected or 4-1BB enriched TIL 3. Bolus high-dose (720,000 IU/kg) IL-2 will be administered to each patient every 8 hours, to tolerance. A maximum of 10 doses will be administered per patient.

Drug: FludarabineRadiation: RadiationBiological: TIL administrationDrug: IL-2

Interventions

FludarabineDRUG

Reduced intensity, myeloablative, lymphodepleting regimen (25 mg/m2 for 3 days)

ACT TIL
RadiationRADIATION

Total Body Radiation (TBR) (2 Gray in a single treatment) for 1 day

ACT TIL
TIL administrationBIOLOGICAL

TIL Administration

ACT TIL
IL-2DRUG

bolus high-dose (720,000 IU/kg) IL-2 is administered to the patients every 8 hours, to tolerance. A maximum of 10 doses are given to the patients.

ACT TIL

Eligibility Criteria

Age18 Years - 80 Years
Sexfemale(Gender-based eligibility)
Gender Eligibility DetailsMetastatic Malignant Ovarian Cancer
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Able to understand and sign the Informed Consent Form.
  • Pathology confirmed epithelial Ovarian/Fallopian Tube/Primary Peritoneal carcinomatosis.
  • For ovarian/peritoneal carcinoma: Platinum- resistant or platinum refractory disease (platinum-resistant disease is defined as disease-progression within 6 months of completion of prior platinum containing regimen, whereas platinum refractory disease is defined as disease progression while on platinum containing regimen or within 3 months from first line, adjuvant chemotherapy).
  • Received and exhausted standard of care therapies for recurrent ovarian cancer and further chemotherapy lines have no proven added value. (For platinum resistant disease, received no more than 3 prior chemotherapy lines, whereas for platinum refractory disease received no more than 2 previous chemotherapy lines).
  • Patients must have at least one lesion that is resectable for TIL generation.
  • Have measurable disease per RECIST 1.1.
  • Patients with one or more brain metastases less than 1 cm each, and any patients with 1 or 2 brain metastases greater than 1 cm must have been treated and stable for 6 weeks.
  • Greater than or equal to 18 years of age.
  • For Patients with child bearing potential, willing to practice birth control from the start of chemotherapy until 120 days after release from the hospital.
  • Life expectancy of greater than three months
  • Performance status of ECOG 0 or 1
  • Adequate organ function defined by lab test results:
  • Hematology:
  • Absolute neutrophil count greater than 1000/mm3 without support of filgrastim Normal WBC greater than 3000/mm3. Hemoglobin greater than 9.0 g/dL Platelet count greater than 100,000/mm3
  • Serology:
  • +6 more criteria

You may not qualify if:

  • Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the non-myeloablative, lymphodepleting induction regimen on the fetus or infant. (Note: Pregnancies occurring in patients with Ovarian cancer are very rare, but possible. For this reason, ELIM has decided to retain the sections dealing with possible cases of pregnancy during the study.)
  • Systemic steroid therapy required (patients who require replacement therapy for adrenal insufficiency may be enrolled if steroid treatment dose do not exceed 10 mg of prednisone or equivalent).
  • Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
  • Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
  • Opportunistic infections (the experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
  • History of severe immediate hypersensitivity reaction to any of the agents used in this study , including history of an anaphylactic reaction to penicillin or gentamicin
  • History of coronary revascularization or ischemic heart disease.
  • Any patient known to have an LVEF less than or equal to 50 percent.
  • Documented LVEF of less than or equal to 50 percent tested in patients with clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
  • Documented FEV1 and DLCO (relative to predicted) less than or equal to 60 percent.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sheba medical Center

Ramat Gan, 5262100, Israel

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

fludarabineRadiationInterleukin-2

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

Physical PhenomenaInterleukinsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsLymphokinesProteinsBiological Factors

Study Officials

  • Jacob Schachter, Prof.

    Sheba Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Jacob Scachter, Prof.

CONTACT

972-3-5304907jacob.schachter@sheba.health.gov.il

Meital Bar

CONTACT

972-3-5305201meital.bar@sheba.health.gov.il

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Head of Ella Lemelbaum Institute for Immuno- Oncology

Study Record Dates

First Submitted

January 21, 2018

First Posted

January 26, 2018

Study Start

January 21, 2018

Primary Completion

February 1, 2021

Study Completion

February 1, 2022

Last Updated

April 4, 2019

Record last verified: 2019-04

Locations

IL(1)