CL-PTL-130: A Multi-Center Phase III, Randomized, Open-Label Trial of Vigil (Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy) in Combination With Irinotecan and Temozolomide as a Second-Line Regimen for Ewing's Sarcoma

Why are we doing this research?

BRIEF SUMMARY:

This is a multicenter, 1:1 randomized Phase III study of intradermal autologous Vigil immunotherapy (1.0 x 10e6 cells/injection; minimum of 4 to a maximum of 12 administrations) in combination with irinotecan and temozolomide in subjects with metastatic Ewing's sarcoma Family of Tumors (ESFT) refractory/intolerant or recurrent to 1 prior line of chemotherapy. Participants undergoing a standard surgical procedure (e.g., tumor biopsy or palliative resection) may have tumor tissue harvested for manufacture of the investigational product, Vigil.


DETAILED DESCRIPTION:

Participants will be managed in an outpatient setting. Hematologic function, liver enzymes, renal function and electrolytes will be monitored. Blood for immune function analyses including IFNγ-ELISPOT analysis of cytotoxic T cell activation in response to autologous tumor antigens will be collected at tissue procurement, post-procurement screening and Day 1 (prior to chemotherapy administration) at Cycles 2, 4, and 6, end of treatment (EOT), 3 months after EOT, and every 6 months thereafter. Blood for ctDNA analysis will be collected at tissue procurement, prior to chemotherapy administration at baseline and on Day 1 prior to chemotherapy administration at Cycles 2, 3, 4, and 6, and EOT.

Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)

Primary Purpose: Treatment

Who can participate?

ELIGIBILITY CRITERIA

Inclusion Criteria:

  • Completed manufacture of at least 4 vials of Vigil.
  • Karnofsky performance status (KPS) / Lansky performance status (LS) ≥80%.
  • Normal organ and marrow function as defined below:
  • Absolute granulocyte count ≥1,500/mm3, Absolute lymphocyte count ≥400/mm3, Platelets ≥100,000/mm3, Total bilirubin ≤ institutional upper limit of normal, AST(SGOT)/ALT(SGPT) ≤2x institutional upper limit of normal, Creatinine <1.5 mg/dL
  • Subject has recovered to CTCAE Grade 1 or better from all adverse events associated with prior therapy or surgery. Pre-existing motor or sensory neurologic pathology or symptoms must be recovered to CTCAE Grade 2 or better.
  • If female of childbearing potential, has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a negative serum test will be required for study entry.
  • Ability to understand and the willingness to sign a written informed protocol specific consent or a parental/guardian informed consent and pediatric assent when appropriate.

Exclusion Criteria:

  • Any anti-neoplastic therapy between tissue procurement for Vigil manufacture and start of study therapy.
  • Live vaccine used for the prevention of infectious disease administered < 30 days prior to the start of study therapy.
  • Post-surgery complication that in the opinion of the treating investigator would interfere with the patient's study participation or make it not in the best interest of the patient to participate.

Ages

  • 2 Years and older

Conditions

  • Adult - Sarcoma Ewing Relapse Relapse - Refractory
  • Sarcoma Ewing Relapse Relapse - Refractory

Contact

Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039
Phone: 513-636-2799
cancer@cchmc.org