NCT03412526

Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Ovarian

A Phase 2, Single-Center, Open Label Study of Autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Ovarian

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Sheba Medical Center · Other Government
• Sex: Female
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Detailed description

The Sponsor is developing the ex-vivo expanded autologous Tumor Infiltrating Lymphocytes (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. 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. 4. Early-stage follow-up until 30 days post-discharge 5. 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.

Conditions

• Metastatic Ovarian Cancer

Interventions

Type	Name	Description
DRUG	Fludarabine	Reduced intensity, myeloablative, lymphodepleting regimen (25 mg/m2 for 3 days)
RADIATION	Radiation	Total Body Radiation (TBR) (2 Gray in a single treatment) for 1 day
BIOLOGICAL	TIL administration	TIL Administration
DRUG	IL-2	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.

Timeline

• Start date: 2018-01-21
• Primary completion: 2021-02-01
• Completion: 2022-02-01
• First posted: 2018-01-26
• Last updated: 2019-04-04

Locations

1 site across 1 country: Israel