Study of Donor Derived, Multi-virus-specific, Cytotoxic T-Lymphocytes for Relapsed/Refractory Neuroblastoma

NCT01460901 | Completed Phase 1 Results DMC

• 2 other identifiers: STALLONe00038
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, investigator-initiated, single-arm, pilot study of post-allogeneic transplant, adoptive immunotherapy for the treatment of patients with relapsed/refractory neuroblastoma expressing the mesenchymal tumor marker GD2. Three patients will be treated. The study will focus on the safety and efficacy of allogeneic, donor derived viral specific cytotoxic T-lymphocytes, retrovirally transduced to express a chimeric antigen receptor specific for disialoganglioside, GD2, expressed on neuroblastoma.

Conditions

Neuroblastoma

Keywords

Neuroblastoma; Relapsed; Refractory

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Immediate and Short Term Toxicity of Infusion Over 8 Weeks

  Immediate: Patients were monitored following infusion to assess for toxicity related to infusion. Potential toxicities related to cellular therapy infusions, such as allergic reaction to the cellular product or cryopreservation media, hemolytic reactions, volume overload, and hemodynamic instability, were monitored. Short Term: Patients were monitored for 8 weeks for short term toxicity related to infusion. Such adverse reactions monitored were acute graft versus host disease and cytokine release syndrome.

  Post infusion week 8

• Peak Transgene Copy Number Per 1000ng PBMC DNA

  Peak Transgene Copy Number per 1000ng PBMC DNA from peripheral blood samples measured during study participation.

  1 year

• Death Within 8 Weeks of Infusion

  8 weeks

Secondary Outcomes (2)

• Peak Viral Specific SFU/2x10e5 Mononuclear Cells Per Well

  up to 1 year

• Maximum Tumor Response (RECIST 1.1)

  1 year

Study Arms (1)

GD2 CAR modified Tri-virus CTL infusion

EXPERIMENTAL

A single infusion of 2x10e6 cells per meter squared was performed 30 to 120 days following allogeneic stem cell transplant.

Biological: GD2 CAR modified Tri-virus specific cytotoxic t-cells

Interventions

GD2 CAR modified Tri-virus specific cytotoxic t-cells BIOLOGICAL

This is a feasibility study to assess safety of an infusion of chimeric-antigen receptor gene modified allogeneic virus specific T lymphocytes after reduced intensity allogeneic stem cell transplant. Three patients were treated and safety was evaluated. Patients received a single infusion of 2x10e6/m2 donor derived, GD2 CAR modified, tri-virus specific CTL performed 30-120 days after allogeneic stem cell transplantation

GD2 CAR modified Tri-virus CTL infusion

Eligibility Criteria

• Age: 18 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Allogeneic transduced tV-CTLs with \>15% expression of 14g2a.zeta chimeric antigen receptor
• Patient or responsible person must be able to understand and sign a permission/assent or consent form for infusion
• Age 18 months through 17 years at time of relapse/progression
• Life expectancy \>8weeks
• Karnofsky score 60% or greater if 10 yrs old or older. Lansky score 60% or greater if under 10 yrs old
• Patient must be HIV negative
• ANC \>500
• Pulse ox\>90% on room air
• AST/ALT/direct bili \<5x upper limit of normal
• Recovered from toxic effects of all prior chemotherapy
• Absence of human/anti-mouse antibody (HAMA) (patients who have received prior therapy with murine antibodies)
• \>50% donor engraftment

You may not qualify if:

• Patient pregnant or lactating or refuses birth control methods
• HIV positive
• Uncontrolled intercurrent infection
• Renal failure (creatinine clearance \<40ml/min/1.73m2)
• Active hepatitis or cirrhosis with bilirubin, AST, ALT \>5xnormal
• Rapidly progressive disease
• Currently receiving any investigational drugs
• Tumor potentially causing airway obstruction
• Cardiomegaly or bilateral pulmonary infiltrates on CXR
• Receiving \>0.25mg/kg/day methylprednisolone or equivalent systemic steroid. Topical steroid therapy is acceptable
• Receiving more than one lymphocyte inhibiting agent (ex. Tacrolimus/CSA and MMF or other similar agent
• Patients relapsing or progressing before the age of 18 months from Stage I/II disease, and/or those who, in the opinion of their oncologist, may benefit from further conventional therapy
• Donor lymphocyte infusion in last 28 days
• Evidence of GvHD greater than or equal to grade 2

Sponsors & Collaborators

• Children's Mercy Hospital Kansas City: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (1)

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Related Links

• Children's Mercy Hospitals and Clinics

MeSH Terms

Conditions

Neuroblastoma; Recurrence

Condition Hierarchy (Ancestors)

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Gary Douglas Myers
• Organization: Children's Mercy Hospitals and Clinics

gdmyers@cmh.edu

8163026817

Study Officials

• Doug Myers, MD

  Children's Mercy Hospital Kansas City

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 25, 2011
• First Posted: October 27, 2011
• Study Start: October 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: July 23, 2019
• Results First Posted: July 23, 2019

Record last verified: 2019-07

Locations

US (1)