Clinical trial NCT00033475: Reduced Immunosuppressive Therapy With or Without Donor White Blood Cells in Treating Patients With Lymphoproliferative Disease After Organ Transplantation
Official title: Cytotoxic T Cell Therapy for Post Transplant Lymphoproliferative Disease: Randomized Controlled Trial in Transplant Recipients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Lymphoproliferative Disorder
Keywords: post-transplant lymphoproliferative disorder
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 50
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Some types of lymphoproliferative disease are associated with Epstein-Barr virus. Combining reduced immunosuppressive therapy with donor white blood cells that have been treated in the laboratory to kill cells infected with Epstein-Barr virus may be an effective treatment for lymphoproliferative disease.

PURPOSE: Randomized phase III trial to compare the effectiveness of reducing immunosuppressive therapy with or without donor white blood cells in treating patients who have Epstein-Barr virus-associated lymphoproliferative disease after organ transplantation.

Detailed description: OBJECTIVES:

* Determine the efficacy of treatment with partially HLA-matched allogeneic cytotoxic T cells and reduction of immunosuppression, in terms of survival rate and time to remission in patients with Epstein-Barr virus-associated B-cell lymphoproliferative disease after solid organ transplantation.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to transplanted organ type and transplant center. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo sliding-scale reduction of immunosuppressive drugs from 1 of 5 regimens at physician's discretion. Patients then receive partially HLA-matched allogeneic cytotoxic T cells IV over 5 minutes once weekly for a total of 4 weeks.
* Arm II: Patients undergo reduction of immunosuppression as in arm I alone. Patients are followed monthly for 6 months and then every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of post-transplant lymphoproliferative disease (PTLD) after solid organ (heart, heart/lung, liver, liver/gut, pancreas, or kidney) transplantation

  * Epstein-Barr virus-positive tumor
  * Newly diagnosed disease
* Measurable disease by clinical methods or radiography
* Must have partially matched donor cytotoxic T cells (CTL) available
* No known panel reactivity to any of the HLA types of CTL available for therapy

PATIENT CHARACTERISTICS:

Age:

* Any age

Performance status:

* Karnofsky 20-100%

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Not specified

Renal:

* Not specified

Other:

* Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* Not specified

Endocrine therapy:

* Not specified

Radiotherapy:

* Not specified

Surgery:

* Not specified

Other:

* No prior therapy for PTLD
* No concurrent antiviral drugs (e.g., acyclovir or ganciclovir) for PTLD

Primary outcomes:
measure: Complete response
measure: Partial response
measure: Stable disease
measure: Progressive disease
measure: Time to complete remission
measure: Survival at 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: England
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
state: England
city: London
country: United Kingdom
facility: Royal Free and University College Medical School
state: England
city: London
country: United Kingdom
facility: King's College Hospital
state: England
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
state: England
city: Manchester
country: United Kingdom
facility: Central Manchester and Manchester Children's University Hospitals NHS Trust
state: England
city: Sheffield
country: United Kingdom
facility: Northern General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Institute of Cancer Research - UK
state: England
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh at Little France
state: Scotland
city: Edinburgh
country: United Kingdom
facility: University of Edinburgh
state: Scotland
city: Edinburgh
country: United Kingdom
facility: University of Edinburgh Laboratory for Clinical and Molecular Virology
state: Scotland
city: Glasgow
country: United Kingdom
facility: Royal Infirmary - Castle
state: Scotland
Study officials:
affiliation: University of Edinburgh
name: Dorothy H. Crawford, MD
role: STUDY_CHAIR
References: