Using Multi-virus Cytotoxic T-cells Following T-Cell Depleted Allogeneic HPCT for Prophylaxis Against EBV, ADV, and CMV

NCT ID: NCT01535885

Last Updated: 2021-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2019-10-31

Brief Summary

This protocol is a phase I study. Patients may be eligible for an infusion of Multi-virus Cytotoxic T Lymphocytes (CTL) if they received a T-cell depleted (TCD) transplant from a related family member or an unrelated donor. Recipients of these types of transplants are severely immune compromised during the early post-transplant period and are more susceptible to certain viruses. The investigators hypothesize that the adoptive transfer of Cytotoxic T Lymphocytes (CTL) against certain viruses: Adenovirus, Cytomegalovirus and Epstein Barr Virus (Ad, CMV, and EBV) will be safe with regard to producing graft versus host disease (GVHD) or other infusion related toxicities.

Detailed Description

Within this clinical trial, the investigators will test the hypotheses that the administration of CTLs for prophylaxis against Ad, CMV and EBV in recipients of TCD-HPCT will be safe and well tolerated. Graded doses of Multi-Virus CTL will be administered to recipients of genotypically haploidentical or mismatched unrelated TCD grafts.

Conditions

Epstein-Barr Virus Infections; Adenovirus; Cytomegalovirus Infections

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Multi-Virus CTLs

The treatment plan delivers a single dose of Multi-Virus CTL to all patients enrolled on study.

Group Type: EXPERIMENTAL

Cytotoxic T Lymphocytes

Intervention Type: BIOLOGICAL

Patients will be studied in cohorts of 3. Eligible patients will receive a single Multi-Virus CTL line infusion 28-100 days after their transplant. The dose will start at dose level 1 (2.0 x 106/kg). After each cohort of 3 patients has been treated at each of the dose levels, decisions will be made if the next high or lower dose level should be used.

Interventions

Cytotoxic T Lymphocytes

Patients will be studied in cohorts of 3. Eligible patients will receive a single Multi-Virus CTL line infusion 28-100 days after their transplant. The dose will start at dose level 1 (2.0 x 106/kg). After each cohort of 3 patients has been treated at each of the dose levels, decisions will be made if the next high or lower dose level should be used.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Patient age < 22 years.
• Both genders and all races are eligible.
• The patient population chosen for the T-cell depleted allogeneic HPCT from a related or unrelated allogeneic donor must meet eligibility based on institutional SOPs and/or the IRB approved T cell depleted allogeneic HPCT protocol which they are enrolled.
• Must be willing to sign a written informed consent.
• Patient Organ Status at the time of enrollment (pre-transplant)

• Lansky or Karnofsky score > 50
• Echocardiogram shortening fraction > 27%
• Renal function: serum creatinine < 2 x normal for age
• DLCO > 50% predicted in patients old enough to comply with PFTs or no baseline oxygen requirement for younger patients.
• Hepatic: AST, ALT < 5x upper limit of normal; bilirubin < 2.0 mg/dl
• Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months following CTL infusion. The male partner should use a condom.
• Patients must be between 28 and 100 days post T-cell depleted allogeneic HPCT
• Patients must meet the following criteria (within 72 hours of CTL infusion):

• Achieved primary engraftment with an ANC of at least 1000 per μl for 3 consecutive days.
• No oxygen requirement with oxygen saturations > 90%.
• AST, ALT < 5x upper limit of normal for age; bilirubin < 2 mg/dl.
• Hemoglobin > 8 gm/dl prior to infusion. (May be transfusion dependent).
• Renal function: serum creatinine < 2 x normal for age.
• The Patient must not have the following conditions on the day of CTL infusion:

• Exhibit overt hematologic manifestations of relapse or persistent disease.
• Evidence of recurrent/persistent disease based primarily on flow cytometry, cytogenetics, chimerism analysis, or other molecular studies does not by itself represent grounds for exclusion.

Exclusion Criteria

• Currently enrolled on another Phase I clinical trial.
• Pregnant or nursing
• Overt hematologic manifestations of relapse or persistent disease
• Having > grade 1 graft-versus-host disease.

• Maximum Eligible Age: 22 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Julie-An M. Talano

Associate Professor of Pediatrics and Director of Clinical Pediatric BMT Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Julie-An Talano, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin/Children's Hospital of Wisconsin

Locations

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

CTL-11/157

Identifier Type: -

Identifier Source: org_study_id