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Trial record 1 of 33 for:    ACT TIL
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Adoptive Cell Therapy Following a Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Melanoma Patients

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Sheba Medical Center
Sponsor:
Information provided by (Responsible Party):
Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT03166397
First received: May 21, 2017
Last updated: May 23, 2017
Last verified: May 2017
  Purpose

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) in combination with lymphodepletion and high-dose interleukin 2 (IL-2) has demonstrated reproducible objective response rates of approximately 50 percent in patients with highly advanced, refractory metastatic melanoma.

Recent developments in theTIL ACT procedure facilitate the use of a reduced-intensity, non-myeloablative, lympho-depleting preparative regimen which is expected to be both less toxic and equally efficient compared to previous regimens.


Condition Intervention Phase
Malignant Melanoma Stage IV Drug: Fludarabine Radiation: Radiation Biological: TIL Drug: IL-2 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 2, Single-Center, Open Label Study of Autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Melanoma Patients

Resource links provided by NLM:


Further study details as provided by Sheba Medical Center:

Primary Outcome Measures:
  • Objective tumor responses [ Time Frame: 3 years ]
    Radiological follow up via CT to determine the sum of Complete Responders (CR) + Partial Responders (PR) + Stable Disease (SD) as assessed by RECIST 1.1

  • Assess adverse events using NCI CTCAE v4.03 during treatment and follow-up [ Time Frame: 3 years ]
    Adverse events will be assessed using NCI CTCAE v4.03 during treatment and follow-up


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: 3 years ]
    Overall survival is defined as the time from study entry until death from any cause

  • Response Rate (RR) [ Time Frame: 3 years ]
    Radiological follow up via CT to determine the sum of Complete Responders (CR) + Partial Responders (PR) as assessed by RECIST 1.1

  • Progression-Free Survival (PFS) [ Time Frame: 3 years ]
    Progression free survival according to RECIST 1.1

  • Quality of Life (QoL) [ Time Frame: 3 years ]
    Assessment of QoL using the EORTC QLQ-MEL38 instrument (specific for Melanoma)


Estimated Enrollment: 30
Anticipated Study Start Date: June 1, 2017
Estimated Study Completion Date: June 1, 2021
Estimated Primary Completion Date: June 1, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACT TIL
  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 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: Fludarabine
Reduced intensity, myeloablative, lymphodepleting regimen
Radiation: Radiation
Total Body Radiation (TBR) (2 Gray as a single treatment) for 1 day
Biological: TIL
TIL administration
Drug: IL-2
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.

Detailed Description:

The Sponsor is developing the ex-vivo expanded autologous TIL as the Investigational Product (IP). Yet, the administration of the TIL cellular product can only be accomplished in the context of an autologous, Adoptive Cell Therapy (ACT) procedure which is composed of the following steps:

  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. Bolus high-dose (720,000 IU/kg) IL-2, which will be administered to each patient every 8 hours, to tolerance. A maximum of 10 doses will be administered per patient.
  3. Early-stage follow-up until 30 days post-discharge
  4. Late-stage follow-up, such as CT scans, will be carried out four and twelve weeks after TIL administration, and then every 3 months thereafter for the first year after TIL therapy; for the second year and onwards, as clinically indicated.
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Measurable metastatic Melanoma with at least one lesion that is resectable for TIL generation.
  2. Refractory to standard treatment
  3. 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.
  4. Greater than or equal to 18 years of age.
  5. Willing to practice birth control from the start of chemotherapy until 120 days after release from the hospital.
  6. Clinical performance status of ECOG 0 or 1
  7. Hematology:

    Absolute neutrophil count greater than 1000/mm3 without support of filgrastim Normal WBC (greater than 3000/mm3). Hemoglobin greater than 8.0 g/dL Platelet count greater than 100,000/mm3

  8. Serology:

    Seronegative for HIV antibody. Seronegative for Hepatitis B or Hepatitis C.

  9. Chemistry:

    Serum ALT/AST less than three times the upper limit of normal (ULN). Serum creatinine less than or equal to 1.6 mg/dL Total bilirubin no more than 1.5 times the ULN, except in patients with Gilbert Syndrome who must have a total bilirubin less than 3 mg/dL.

  10. Negative pregnancy test in women of child bearing potential because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
  11. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo). Patients may have undergone minor surgical procedures with the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.

Exclusion Criteria:

  1. 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.
  2. Systemic steroid therapy required.
  3. 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.
  4. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
  5. 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.)
  6. 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
  7. History of coronary revascularization or ischemic symptoms
  8. Any patient known to have an LVEF less than or equal to 50 percent .
  9. 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
  10. Documented FEV1 and DLCO (relative to predicted) less than or equal to 60 percent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03166397

Contacts
Contact: Meital Bar 972-3-5305201 meiral.bar@sheba.health.gov.il

Locations
Israel
Sheba Medical Center Recruiting
Ramat Gan, Israel, 5262100
Contact: Meital Bar    972-3-5305201    meital.bar@sheba.health.gov.il   
Principal Investigator: Jacob Schachter, MD         
Sponsors and Collaborators
Sheba Medical Center
  More Information

Responsible Party: Sheba Medical Center
ClinicalTrials.gov Identifier: NCT03166397     History of Changes
Other Study ID Numbers: SHEBA-16-3566-JS-CTIL
Study First Received: May 21, 2017
Last Updated: May 23, 2017
Individual Participant Data  
Plan to Share IPD: Undecided
Plan Description: To be considered

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Fludarabine
Fludarabine phosphate
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 23, 2017