Safety, Toxicity and MTD of One Intravenous IV Injection of Donor CTLs Specific for CMV and Adenovirus

NCT00880789 | Completed Phase 1 DMC

• 1 other identifier: 23668-ACT CAT
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

With this study, we want to see if we can use a kind of white blood cell called T cells to prevent or treat AdV and CMV infection. We will grow these T cells from the cord blood before the patients transplant. These cells have been trained to attack adenovirus/CMV-infected cells and are called Adenoviral/CMV-specific cytotoxic (killer) T-cells or "AdV/CMV-CTL." We would plan to give the patient one dose of AdV/CMV-CTL any time from 30 days after their transplant. We have used T cells made in this way from the blood of donors to prevent infections in patients who are getting a bone marrow or blood stem cell transplant but this will be the first time we make them from cord blood.

Conditions

Cytomegalovirus Infection; Adenovirus Infection

Keywords

Cord Blood Transplant; cytomegalovirus; CMV; Adenovirus; ADV

Outcome Measures

Primary Outcomes (1)

• To determine safety, toxicity and MTD of one intravenous injection of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV and Adenovirus given to patients with or at risk for CMV and adenovirus disease after cord blood transplant

  1 year

Secondary Outcomes (3)

• To evaluate the feasibility of generating a sufficient number of umbilical cord blood-derived cytotoxic T lymphocytes (CTLs) specific for CMV and Adenovirus

  1 year

• To evaluate the impact of these CTLs on Adenovirus-specific T-lymphocyte immune reconstitution.

  1 year

• To evaluate the recovery of virus-specific immunity after CTL infusion and its correlation with viral clearance and/or protection from viral infection/disease.

  1 year

Study Arms (1)

Dose Level One: 5x10^6/m2

EXPERIMENTAL

CTL Dose Given from Day +30 post SCT (stem cell transplant). For the trial, two patients are allocated in each cohort and are followed for 30 days post IV injection of transduced T-cells for evaluation of DLTs. A maximum 18 patients will be accrued into each group. The final MTD will be the dose with probability closest to the target toxicity rate at these termination points. The trial continues until a minimum of 12 patients have been treated. The trial will stop when the maximum 18 patients have been treated, or when six patients have been treated at the current MTD. We therefore expect to enroll between 12-18 patients into this trial.

Biological: CMV/AdV specific T cells

Interventions

CMV/AdV specific T cells BIOLOGICAL

CTL Dose Given from Day +30 post SCT (stem cell transplant). For the trial, two patients are allocated in each cohort and are followed for 30 days post IV injection of transduced T-cells for evaluation of DLTs. A maximum 18 patients will be accrued into each group. The final MTD will be the dose with probability closest to the target toxicity rate at these termination points. The trial continues until a minimum of 12 patients have been treated. The trial will stop when the maximum 18 patients have been treated, or when six patients have been treated at the current MTD. We therefore expect to enroll between 12-18 patients into this trial.

Dose Level One: 5x10^6/m2

Eligibility Criteria

• Age: Up to 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with malignant or nonmalignant diseases who are candidates for transplant.
• Patients must have a single CB unit matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. The unit must be cryopreserved in two fractions, with a minimum of 2.5x10\^7 total nucleated cells per kg pre-thaw in the fraction which will be used for the primary transplant. The remaining fraction will be used to generate the CTLs to give at day 30 or beyond as described below.
• Recipients of a single cord blood unit fractionated into 2 fractions (i.e. from a HLA matched or mismatched unrelated donor) transplant at risk for or with CMV/Adenoviral disease or reactivation.
• Lansky/Karnofsky scores 60 or greater
• Absolute neutrophil count (ANC) greater than 500/ul.
• No evidence of GVHD \> Grade II at time of enrollment.
• Life expectancy \> 30 days
• Absence of severe renal disease (Creatinine \> x 3 normal for age)
• Absence of severe hepatic disease. Direct bilirubin must be less than 3 mg/dl and AST less than 5x upper limit of normal
• Patient must be at least 30 days post transplant to be eligible to receive CTL
• Written informed consent and/or signed assent line from patient, parent or guardian.
• Patient not on Fi02 of \>60%

You may not qualify if:

• Pregnant or Lactating
• Patients with active central nervous system disease
• Patients with Karnofsky performance status \<70%
• Patients with grade 3 or 4 or primary myelofibrosis
• Patients with suitable related donors
• Pregnant or lactating
• Unable to wean steroids to 0.5 mg/kg/day or less prednisone.
• Patients with other uncontrolled infections (except CMV and/or adenovirus and/or EBVemia in absence of PTLD). For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
• Patients with less than 50% donor chimerism in either peripheral blood or bone marrow or patients with relapse of original disease.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Cytomegalovirus Infections; Adenoviridae Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Caridad A. Martinez, MD

  Baylor College of Medicine - Texas Children's Hospital

  PRINCIPAL INVESTIGATOR

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: Prinicipal Investigator

Study Record Dates

• First Submitted: April 13, 2009
• First Posted: April 14, 2009
• Study Start: May 1, 2009
• Primary Completion: August 1, 2013
• Study Completion: June 1, 2014
• Last Updated: October 15, 2014

Record last verified: 2014-10

Locations

US (2)