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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
Information provided by (Responsible Party):
Chrystal Louis, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00703222
First received: June 20, 2008
Last updated: February 3, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Neuroblastoma
Biological: SJNB-JF-IL2 and SJNB-JF-Lptn cells and SKNLP Unmodified Neuroblastoma Cell Lines
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Evaluate the immune response to these immunizations. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Estimate 3 year progression free survival (PFS) in vaccinated patients. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Estimate 3 year overall survival (OS) in vaccinated patients. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Evaluate changes in minimal residual disease load by polymerase chain reaction pre- and post-vaccination. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 7
Study Start Date: June 2008
Estimated Study Completion Date: July 2028
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Neuroblastoma vaccine
SJNB-JF-IL2 and SJNB-JF-Lptn cells and SKNLP Unmodified Neuroblastoma Cell Lines
Biological: SJNB-JF-IL2 and SJNB-JF-Lptn cells and SKNLP Unmodified Neuroblastoma Cell Lines

*SJNB-JF-IL2 and SJNB-JF-Lptn cells are each dosed at 1x10e7 cells/m2/vaccination. This will be given in conjunction with an escalating dose of SKNLP vaccine.

  • Dose Level 1: 1x10e6 cells/m2/vaccination dose of SKNLP Unmodified Neuroblastoma Cell Line Vaccine Component
  • Dose Level 2: 1x10e7 cells/m2/vaccination dose of SKNLP Unmodified Neuroblastoma Cell Line Vaccine Component

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Age <21 years at time of diagnosis

Histological proof of high-risk neuroblastoma at diagnosis (see Appendices A and B in Full Protocol attached in Section S.)

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

  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: NCT00703222

Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
Investigators
Principal Investigator: Chrystal U Louis, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Chrystal Louis, Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00703222     History of Changes
Other Study ID Numbers: 22053-CHESAT
Study First Received: June 20, 2008
Last Updated: February 3, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
high-risk neuroblastoma
single autologous stem cell rescue

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 18, 2014