A Study Using Allogenic-Cytomegalovirus (CMV) Specific Cells for Glioblastoma Multiforme (GBM)

Study Overview
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Brief Summary
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The primary purpose of this study is to determine the safety and efficacy of the infusion of partially matched, allogeneic, CMV specific cytotoxic T cells (CTL) for patients with GBM that have failed primary therapy.

Detailed Description
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Tumor specimens of consenting patients will be tested by immunohistochemistry (IHC) for the presence of IE-1 and/or pp65. Subjects whose tumors test positive for either or both CMV antigens will be consented for the treatment phase which will include a regimen of fludarabine and cyclophosphamide daily for two days, cyclophosphamide only for a third day, followed by one day of rest prior to the day of CTL infusion. This trial intended to be a Phase 1/2 trial, but it never progressed to Phase 2 before termination.

Official Title
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A Phase I-II Study of Allogeneic CMV Specific Cytotoxic T Lymphocytes (CTL) for Patients With Refractory Glioblastoma Multiforme (GBM)

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Drug: Fludarabine
* Drug: Cyclophosphamide
* Biological: CMV Specific Cytotoxic T Lymphocytes (CTL)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: FOR SCREENING Patients must have a histopathologic diagnosis of GBM. Patients from 5 to 65 years of age with GBM. FOR TREATMENT GBM has progressed following primary therapy. Tumor is CMV pp65 or IE1 positive by immunohistochemistry (IHC). Subjects must have pulse oximetry > or = 94 % on no supplemental oxygen. Creatinine clearance must be > 50 cc/min as estimated by patient's serum creatinine, weight, and age. Bilirubin must be < 2.0 mg/dl and SGOT/SGPT < 2.5 X normal. ECOG performance status must be < or = 2, and for patients <16 years of age, Lansky performance status must be > or = 70%. Exclusion Criteria: Pregnant females Subjects who are moribund or who because of cardiac, pulmonary, renal, hepatic or neurologic dysfunction are not expected to survive one month following the T cell infusion

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GBM Treatment<br> | Drug: Fludarabine<br>* 30 mg/m2<br>Drug: Cyclophosphamide<br>* 600 mg/m2<br>Biological: CMV Specific Cytotoxic T Lymphocytes (CTL)<br>* CTL Infusion (3 - 5 x 10E6 cells/kg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the incidence of tumor responses, as defined as stable disease, partial, or complete responses after the infusion of CMV CTL. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the duration and magnitude of donor chimerism post infusion by micro chimerism assays. |  | 2 years | 
| To determine the incidence of increases in CMV pp65 or IE-1 T cells post infusion of allogeneic CMV CTL of GBM patients. |  | 2 years | 
| To determine safety of allogeneic CTL infusions in this patient population. |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioblastoma multiforme, GBM, Cytomegalovirus, CMV, Cytotoxic T lymphocyte, CTL