Clinical trial NCT00066469: Cyclophosphamide, Rituximab, and Either Prednisone or Methylprednisolone in Treating Patients With Lymphoproliferative Disease After Solid Organ Transplantation
Official title: Phase II Study of Cyclophosphamide, Prednisone and Rituximab (CPR) in Children, Adolescents and Young Adults With B-lymphocyte Antigen CD20 (CD20) Positive Post-Transplant Lymphoproliferative Disease (PTLD) Following Solid Organ Transplantation (SOT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoproliferative Disorder
Keywords: post-transplant lymphoproliferative disorder
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-08-07
Enrollment: 55
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy such as cyclophosphamide, prednisone, and methylprednisolone use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining cyclophosphamide and either prednisone or methylprednisolone with rituximab may be effective in treating lymphoproliferative disease following organ transplantation.

PURPOSE: Phase II trial to study the effectiveness of combining cyclophosphamide and either prednisone or methylprednisolone with rituximab in treating patients who have Epstein-Barr virus-positive lymphoproliferative disease following organ transplantation.

Detailed description: OBJECTIVES:

* Determine the safety and toxicity of cyclophosphamide, rituximab, and prednisone or methylprednisolone in patients with CD20-positive and Epstein-Barr virus-positive post-transplant lymphoproliferative disease (PTLD) after solid organ transplantation.
* Determine the 2-year event-free survival, defined as alive and in continuous complete remission with a functioning original allograft, of patients treated with this regimen.
* Determine the response rate in patients treated with this regimen.
* Determine the PTLD gene expression profile by microarray analysis and fluorescent in situ hybridization in patients treated with this regimen.
* Determine the accrual rate of patients to this study.

OUTLINE: This is a multicenter study.

Patients receive cyclophosphamide IV over 30-60 minutes on day 1 and oral prednisone or methylprednisolone IV twice daily on days 1-5. During courses 1 and 2 only, patients also receive rituximab IV over 2-5 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression, a new primary or secondary malignancy, or unrelated disease.

After finishing study treatment, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: A total of 60 patients (50 with non-fulminant post-transplant lymphoproliferative disease \[PTLD\] and 10 fulminant PTLD) will be accrued for this study within 2.5-3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed post-transplant lymphoproliferative disease (PTLD)

  * Presents with 1 of the following:

    * Fulminant PTLD (F-PTLD)

      * Fever greater than 38°C
      * Hypotensive (for age)
      * Evidence of multiple organ involvement/failure, including at least 2 of the following:

        * Marrow (including pancytopenia without detectable B-cell proliferation)
        * Liver (coagulopathy, transaminitis, and/or hyperbilirubinemia)
        * Lungs (interstitial pneumonitis with or without pleural effusions)
        * Gastrointestinal tract hemorrhage
    * Non-fulminant PTLD (NF-PTLD)

      * Does not meet the above F-PTLD criteria
      * Considered medically refractory to reduced immune suppression (50% or more reduction of immunosuppression) for at least 1 week
* CD20 positive AND Epstein-Barr virus positive
* Must have received prior solid organ transplantation
* Must have residual disease after biopsy and/or surgery
* No PTLD central nervous system (CNS) disease, defined as positive cytology and/or radiographic evidence

PATIENT CHARACTERISTICS:

Age

* Under 31

Performance status

* Not specified

Life expectancy

* NF-PTLD patients:

  * At least 8 weeks

Hematopoietic

* See Disease Characteristics

Hepatic

* See Disease Characteristics

Renal

* Not specified

Pulmonary

* See Disease Characteristics

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

* More than 1 month since prior rituximab

Chemotherapy

* More than 4 weeks since prior chemotherapy and recovered

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* See Disease Characteristics

Primary outcomes:
measure: Event-free Survival
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Downey
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Institute at Loma Linda University Medical Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Medical Center - Oakland
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Center for Cancer and Blood Disorders
state: Colorado
city: Wilmington
country: United States
facility: Alfred I. duPont Hospital for Children
state: Delaware
city: Fort Myers
country: United States
facility: Lee Cancer Care of Lee Memorial Health System
state: Florida
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
city: Pensacola
country: United States
facility: Sacred Heart Cancer Center at Sacred Heart Hospital
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Chicago
country: United States
facility: Children's Memorial Hospital - Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Springfield
country: United States
facility: Simmons Cooper Cancer Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: Alexandria
country: United States
facility: Tulane Cancer Center Office of Clinical Research
state: Louisiana
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital at University of Michigan Medical Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Cancer Clinic
state: Mississippi
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Sunrise Hospital and Medical Center
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center Cancer Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center and Children's Hospital
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Knoxville
country: United States
facility: East Tennessee Children's Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Corpus Christi
country: United States
facility: Driscoll Children's Hospital
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Charleston
country: United States
facility: West Virginia University Health Sciences Center - Charleston
state: West Virginia
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
city: Westmead
country: Australia
facility: Westmead Institute for Cancer Research at Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Children's Hospital
state: Queensland
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Children's & Women's Hospital of British Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Montreal Children's Hospital at McGill University Health Center
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
city: Auckland
country: New Zealand
facility: Starship Children's Health
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
Study officials:
affiliation: Nationwide Children's Hospital
name: Thomas G. Gross, MD, PhD
role: STUDY_CHAIR
References:
citation: Gross TG, Orjuela MA, Perkins SL, Park JR, Lynch JC, Cairo MS, Smith LM, Hayashi RJ. Low-dose chemotherapy and rituximab for posttransplant lymphoproliferative disease (PTLD): a Children's Oncology Group Report. Am J Transplant. 2012 Nov;12(11):3069-75. doi: 10.1111/j.1600-6143.2012.04206.x. Epub 2012 Aug 6.