Clinical trial NCT01535885: Using Multi-virus Cytotoxic T-cells Following T-Cell Depleted Allogeneic HPCT for Prophylaxis Against EBV, ADV, and CMV
Official title: A Phase I Study Of Using Multi-virus Cytotoxic T-cells Following T-cell Depleted Allogeneic Hematopoietic Progenitor Cell Transplantation For Prophylaxis Against Specific Pathogens- Epstein Barr Virus, Adenovirus, And Cytomegalovirus (ACE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Epstein-Barr Virus Infections
Adenovirus
Cytomegalovirus Infections
Keywords: Cytoxic T Lymphocytes(CTL)
T-cell Depleted
Allogeneic Transplant
Epstein Barr Virus
Adenovirus
Cytomegalovirus
Hematopoietic progenitor cell transplantation
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
First posted: 2012-02-20
Enrollment: 25
Sex: ALL
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: To assess toxicity by SAEs scored according to the adaptive CTCAE version 5
timeFrame: 1 year
Secondary outcomes:
measure: Evidence of immunity against specific viral pathogens- Ad, CMV and EBV in recipients of Multi-Virus CTLs
timeFrame: 1 year
measure: The incidence of Ad, EBV, and CMV systemic infections during the first 180 days post-transplant
timeFrame: 1 year
Other outcomes:
Locations:
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin/Children's Hospital of Wisconsin
name: Julie-An Talano, MD
role: PRINCIPAL_INVESTIGATOR
References: