A Two-part Phase IIb Trial of Vigil (Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy) in Ewing's Sarcoma

NCT02511132 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CL-PTL-121
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 6

Brief Summary

A two-part trial in patients with metastic Ewing's sarcoma. Participants in Part 1 will be randomized to receive either Vigil immunotherapy or gemcitabine and docetaxel with the objective of comparing the overall survival between the two arms. Participants enrolled in Part 2 will receive Vigil immunotherapy in combination of temozolomide and irinotecan with the objective to determine the safety profile of the combination treatment.

Conditions

Ewing's Sarcoma

Keywords

Ewing's Sarcoma Family of Tumors, ESFT, Sarcoma; Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events Determined by Laboratory Assessments and Physical Examinations

  To determine safety profile of Vigil immunotherapy in combination with irinotecan and temozolomide with 30 days of last dose in patients with metastatic Ewing's sarcoma refractory or intolerant to at least 1 prior line of systemic chemotherapy. • To determine safety profile of Vigil immunotherapy in combination with irinotecan and temozolimidetemozolomide in patients with metastatic Ewing's sarcoma refractory or intolerant to at least 1 prior line of systemic chemotherapy.

  30 days of last treatment dosing

Secondary Outcomes (2)

• Progression Free Survival

  Estimated median 1.3 years

• Overall Survival

  Estimated median 2 years

Study Arms (3)

Part 1: Vigil Alone

EXPERIMENTAL

Vigil immunotherapy 1.0 x 107 cells/injection; minimum of 4 to a maximum of 12 administrations every 28 days

Biological: Vigil

Part 1: Gemicitabine and Docetaxel

ACTIVE COMPARATOR

Gemcitabine 675 mg/m2 IV at 10 mg/m2/min D1 and Docetaxel 75 mg/m2 IV starting on D8 and given every 21 days.

Drug: Gemcitabine; Drug: Docetaxel

Part 2: Vigil plus Temozolomide and Irinotecan

EXPERIMENTAL

(i) oral temozolomide 100 mg/m2 daily (Days 1 - 5, total dose 500 mg/m2/cycle), (ii) irinotecan 50 mg/m2 daily (Days 1 - 5, total dose 250mg/m2/cycle), orally or irinotecan 20mg/m2 daily (Days 1 - 5, total dose 100mg/m2/cycle ), intravenously (iii) peg-filgrastim 100μg/kg (Day 6) subcutaneously (optional and may be administered at home), and (iv) Vigil 1.0 x 107 cells/injection, intradermally on Day 15 and every 3 weeks thereafter. One cycle = 21 days.

Biological: Vigil; Drug: Temozolomide; Drug: Irinotecan

Interventions

Vigil BIOLOGICAL

Vigil 1.0 x 10e7 cells/injection, minimum of 4 to a maximum of 12 administrations.

Also known as: formerly known as FANG™, bi-shRNAfurin and GMCSF Autologous Tumor Cell Immunotherapy

Part 1: Vigil Alone; Part 2: Vigil plus Temozolomide and Irinotecan

Temozolomide DRUG

oral temozolimidetemozolomide 100 mg/m2 daily (Days 1 - 5, total dose 500 mg/m2/cycle)

Also known as: TEMODAR

Part 2: Vigil plus Temozolomide and Irinotecan

Irinotecan DRUG

irinotecan 50 mg/m2 daily (Days 1 - 5, total dose 250mg/m2/cycle), orally or irinotecan 20mg/m2 daily (Days 1 - 5, total dose 100mg/m2/cycle ), intravenously

Also known as: CAMPTOSAR

Part 2: Vigil plus Temozolomide and Irinotecan

Gemcitabine DRUG

675 mg/m2 IV at a rate of 10 mg/m2/min on Day 1 and Day 8 every 21 days

Also known as: GEMZAR

Part 1: Gemicitabine and Docetaxel

Docetaxel DRUG

75 mg/m2 IV administered on Day 8 and every 21 days

Also known as: TAXOTERE

Part 1: Gemicitabine and Docetaxel

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be eligible for tissue procurement for the Vigil manufacturing process, if they meet all of the following criteria:
• Histologically confirmed Ewing's Sarcoma Family of Tumors (ESFT)
• Age ≥2 years
• Estimated survival ≥ 6 months
• Evidence of EWS translocation by FISH or RT-PCR or Next Generation Sequencing (NGS) Metastatic disease
• Refractory or intolerant to ≥ 2 lines of systemic chemotherapy (Part 1) or Refractory or intolerant to at least 1 line of systemic chemotherapy (Part 2)
• Planned standard of care surgical procedure (e.g., tumor biopsy or palliative resection or thoracentesis) and expected availability of a cumulative mass of \~10-30 grams tissue ("golf-ball" size) or pleural fluid estimated volume ≥ 500mL (must be primary tap) for immunotherapy manufacture
• Tumor intended for immunotherapy manufacture is not embedded in bone and does not contain luminal tissue (e.g., bowel, ureter, bile duct)
• Ability to understand and the willingness to sign a written informed consent document for tissue harvest

You may not qualify if:

• Patients meeting any of the following criteria are not eligible for tissue procurement for the Vigil manufacturing:
• Medical condition requiring any form of chronic systemic immunosuppressive therapy (steroid or other) except physiologic replacement doses of hydrocortisone or equivalent (no more than 30 mg hydrocortisone or 10 mg prednisone equivalent daily) for \< 30 days duration
• Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected
• Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months
• Any documented history of autoimmune disease with exception of Type 1 diabetes on stable insulin regimen, hypothyroidism on stable dose of replacement thyroid medication, vitiligo, or asthma not requiring systemic steroids
• Known history of allergies or sensitivities to gentamicin
• Known hypersensitivity reactions to docetaxel or to other drugs formulated with polysorbate 80 that would preclude treatment with docetaxel (Part 1 only)
• History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
• Known HIV or chronic Hepatitis B or C infection
• Successful manufacturing of at least 4 vials of Vigil
• Karnofsky performance status (KPS) ≥60% (Part 1) or KPS ≥80% (Part 2)
• Estimated survival ≥ 4 months (Part 1) or estimated survival of ≥6 months (Part 2)
• Normal organ and marrow function as defined below:
• Absolute granulocyte count ≥1,500/mm3
• Absolute lymphocyte count ≥400/mm3

Sponsors & Collaborators

• Gradalis, Inc.: lead

Study Sites (6)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Nicklaus Children's Hospital (Miami Children's Health System)

Miami, Florida, 33155, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cleveland Clinic Children's

Cleveland, Ohio, 44195, United States

Location

Mary Crowley Cancer Research Centers

Dallas, Texas, 75230, United States

Location

TOPA - Medical City Dallas Pediatric Hematology-Oncology

Dallas, Texas, 75230, United States

Location

Related Publications (4)

• Ghisoli M, Barve M, Schneider R, Mennel R, Lenarsky C, Wallraven G, Pappen BO, LaNoue J, Kumar P, Nemunaitis D, Roth A, Nemunaitis J, Whiting S, Senzer N, Fletcher FA, Nemunaitis J. Pilot Trial of FANG Immunotherapy in Ewing's Sarcoma. Mol Ther. 2015 Jun;23(6):1103-1109. doi: 10.1038/mt.2015.43. Epub 2015 Mar 19.

  PMID: 25917459 BACKGROUND

• Senzer N, Barve M, Kuhn J, Melnyk A, Beitsch P, Lazar M, Lifshitz S, Magee M, Oh J, Mill SW, Bedell C, Higgs C, Kumar P, Yu Y, Norvell F, Phalon C, Taquet N, Rao DD, Wang Z, Jay CM, Pappen BO, Wallraven G, Brunicardi FC, Shanahan DM, Maples PB, Nemunaitis J. Phase I trial of "bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell" vaccine (FANG) in advanced cancer. Mol Ther. 2012 Mar;20(3):679-86. doi: 10.1038/mt.2011.269. Epub 2011 Dec 20.

  PMID: 22186789 BACKGROUND

• Ghisoli M, Barve M, Mennel R, Lenarsky C, Horvath S, Wallraven G, Pappen BO, Whiting S, Rao D, Senzer N, Nemunaitis J. Three-year Follow up of GMCSF/bi-shRNA(furin) DNA-transfected Autologous Tumor Immunotherapy (Vigil) in Metastatic Advanced Ewing's Sarcoma. Mol Ther. 2016 Aug;24(8):1478-83. doi: 10.1038/mt.2016.86. Epub 2016 Apr 25.

  PMID: 27109631 BACKGROUND

• Ghisoli M, Rutledge M, Stephens PJ, Mennel R, Barve M, Manley M, Oliai BR, Murphy KM, Manning L, Gutierrez B, Rangadass P, Walker A, Wang Z, Rao D, Adams N, Wallraven G, Senzer N, Nemunaitis J. Case Report: Immune-mediated Complete Response in a Patient With Recurrent Advanced Ewing Sarcoma (EWS) After Vigil Immunotherapy. J Pediatr Hematol Oncol. 2017 May;39(4):e183-e186. doi: 10.1097/MPH.0000000000000822.

  PMID: 28338569 BACKGROUND

MeSH Terms

Conditions

Sarcoma, Ewing; Sarcoma

Interventions

FANG vaccine; Temozolomide; Irinotecan; Gemcitabine; Docetaxel

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Limitations and Caveats

Due to limited accrual to Part 1 of this study (rare disease), Gradalis opened Part 2 of this clinical protocol to assess the safety of Vigil immunotherapy in combination with irinotecan and temozolomide. Both parts of the study led to small numbers of subjects analyzed.

Results Point of Contact

• Title: Clinical and Regulatory Operations
• Organization: Gradalis, Inc.

info@gradalisinc.com

214-442-8100

Study Officials

• John Nemunaitis, MD

  Gradalis, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1: Participants will be randomized 1:1 to receive Vigil immunotherapy alone or gemcitabine / docetaxel. Part 2 participants will be a single group of subjects to receive Vigil immunotherapy in combination with irinotecan and temozolomide.

Study Record Dates

• First Submitted: July 28, 2015
• First Posted: July 29, 2015
• Study Start: February 10, 2016
• Primary Completion: November 12, 2018
• Study Completion: December 23, 2020
• Last Updated: December 22, 2022
• Results First Posted: July 22, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)