A Phase I/II Study Of Immunization With Lymphotactin And Interleukin 2 Gene Modified Neuroblastoma Tumor Cells (CHESAT)

A Phase I/II Study Of Immunization With Lymphotactin And Interleukin 2 Gene Modified Neuroblastoma Tumor Cells After High-Dose Chemotherapy And Autologous Stem Cell Rescue In Patients With High Risk Neuroblastoma

The investigators intend to test the safety, and immunologic and clinical efficacy of a combination of 2 allogeneic neuroblastoma tumor cell line vaccines, one of which has been genetically modified to secrete the cytokine/chemokine combination of IL-2 and lymphotactin, in patients undergoing chemotherapy for newly diagnosed, high risk neuroblastoma who receive single autologous stem cell rescue as consolidation therapy.

This protocol will be carried out as a Phase I/IIa study to evaluate the safety and toxicity of adding a previously unstudied, unmodified, irradiated neuroblastoma cell line (SKNLP) to a studied, safe dose of a gene modified, IL-2/Lptn secreting neuroblastoma cell line SJNB-JF-IL2/Lptn to be given as a vaccine to patients diagnosed with high risk neuroblastoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Neuroblastoma
• Intervention / Treatment: Biological: SNJB-JF-IL2 and SJNB-JF-Lptn + Dose Level 1 SKNLP; Biological: SNJB-JF-IL2 and SJNB-JF-Lptn + Dose Level 2 SKNLP

Detailed Description

TREATMENT PLAN: Standard Chemotherapy for Neuroblastoma: Standard therapy for neuroblastoma is given in 3 phases: induction, consolidation, and maintenance. For enrollment in this vaccine study patients and their physicians must anticipate therapy that will include consolidation with high dose chemotherapy with stem cell rescue. They will be eligible for enrollment in the phase I or phase II trial of vaccination with gene modified and unmodified, allogeneic neuroblastoma cell lines. Patients will receive Induction, Consolidation, and Maintenance therapy per their institutional standards. A general description of the therapy follows:

• Induction: Induction consists of multiple cycles of induction chemotherapy with harvest of autologous stem cells immediately following a particular cycle of chemotherapy per institutional standards. Local control of the tumor with radiation therapy and/or surgery occurs following a few cycles of induction chemotherapy or immediately prior to consolidation therapy.
• Consolidation: Consolidation must consist of high dose chemotherapy with autologous stem cell rescue (HDT/SCR).
• Maintenance: Starting day +90 after HDT/SCR, patients will be treated with Isotretinoin (Cis-Retinoic Acid, CRA).

VACCINE DOSING: Vaccine components SJNB-JF-IL2 and SJNB-JF-Lptn will each be dosed at 1x10e7 cells/m2. This will be given in conjunction with an escalating dose of SKNLP vaccine in the phase I portion of this study. In the phase II portion of this study, the same dose of SJNB-JF-IL2 and SJNB-JF-Lptn will be given in conjunction with the highest dose of SKNLP determined in the phase I portion. Vaccination will be administered on an inpatient or outpatient basis. Patient will be notified of which dose of vaccine cells they will receive if enrolled in the study.

Phase I Dose Escalation Component: While the investigators do not suspect that addition of a second irradiated, unmodified neuroblastoma tumor cell line to the previously tested SJNB-JF gene modified cell line will affect the safety profile of the vaccine, as the SKNLP has not been tested previously in vaccine studies, the investigators will perform an abbreviated dose escalation study of the combined vaccine to assess safety. The investigators know that the vaccine given to patients whose neuroblastoma returned was safe. The vaccine that was given to those patients was treated with the viruses to make cytokines. The investigators have never used the 2nd cell group in patients. Because of this, the investigators plan to treat 3 to 6 patients at a lower dose of cells to see if adding the second cell line is safe to give.

• Dose Level 1 (3-6 patients) 1x10e6 cells/m2/vaccination dose of SKNLP Unmodified Neuroblastoma Cell Line Vaccine Component

• Dose Level 2 (3-6 patients) 1x10e7 cells/m2/vaccination dose of SKNLP Unmodified Neuroblastoma Cell Line Vaccine Component

  • SJNB-JF-IL2 and SJNB-JF-Lptn cells are each dosed at 1x10e7 cells/m2/vaccination

Duration of Therapy: In the absence of treatment delays due to adverse events, treatment may continue with immunizations per the treatment plan up to 12 vaccinations or until one of the following criteria applies: - Disease progression - Intercurrent illness that prevents further administration of treatment - Unacceptable adverse events(s) including but not limited to grade 3-4 non-hematologic toxicity according to CTCAE v3.0. Grade 3 rigors/chills will be tolerated for 48-72 hours if attributed to vaccination. - Patient decides to withdraw from the study - General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgement of the investigator.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Age <21 years at time of diagnosis

Histological proof of high-risk neuroblastoma at diagnosis

Anticipating single autologous stem cell rescue following high dose consolidation chemotherapy

Meet all eligibility criteria for high dose chemotherapy with stem cell rescue per institutional standard

Signed informed consent

Patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.

HIV negative

Exclusion Criteria:

Patients must not be currently receiving any investigational agents or have received any tumor vaccines within the previous six months

Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Pregnant

HIV-positive patients regardless of treatment status

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1; SNJB-JF-IL2 and SJNB-JF-Lptn + Dose Level 1 SKNLP	Biological: SNJB-JF-IL2 and SJNB-JF-Lptn + Dose Level 1 SKNLP; SJNB-JF-IL2 and SJNB-JF-Lptn at 1 x 10^7 cells/m2 SKNLP at 1 x 10^6 cells/m2
Experimental: Dose Level 2; SNJB-JF-IL2 and SJNB-JF-Lptn + Dose Level 2 SKNLP	Biological: SNJB-JF-IL2 and SJNB-JF-Lptn + Dose Level 2 SKNLP; SJNB-JF-IL2 and SJNB-JF-Lptn at 1 x 10^7 cells/m2 SKNLP at 1 x 10^7 cells/m2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the safety of repeated immunization with gene-modified, IL-2/lymphotactin secreting SJNB-JF-IL2 and SJNB-JF-Lptn cells co-administered with the unmodified SKNLP neuroblastoma cell line.	21-day window following the first vaccination will constitute the time period for DLT assessment. Dose limiting toxicity will be any grade 3 or 4 non-hematologic toxicity as per the CTCAE v3.0 or a grade 3 injection site toxicity per the CTCAE 3.0. Toxicities after the initial as well as after subsequent vaccinations will be summarized separately.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the immune response to these immunizations.	Summarize ELISPOT levels of CTLp at baseline and each time point of assessment.	1 year

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: Center for Cell and Gene Therapy, Baylor College of Medicine
• Investigators: Principal Investigator: Andras A. Heczey, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): May 1, 2011
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: June 20, 2008
• First Submitted That Met QC Criteria: June 20, 2008
• First Posted (Estimated): June 23, 2008

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: high-risk neuroblastoma; single autologous stem cell rescue
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Neuroblastoma; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Interleukin-2
• Other Study ID Numbers: 22053-CHESAT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We will not share IPD with other researchers. Study outcomes will be published in aggregate.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes