Cyclophosphamide, Rituximab, and Either Prednisone or Methylprednisolone in Treating Patients With Lymphoproliferative Disease After Solid Organ Transplantation

NCT ID: NCT00066469

Last Updated: 2019-08-06

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

55 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-04-30

Study Completion Date

2013-12-31

Brief Summary

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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

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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.

Conditions

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Lymphoproliferative Disorder

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cyclophosphamide, prednisone, rituximab

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

Group Type EXPERIMENTAL

rituximab

Intervention Type BIOLOGICAL

Cycles 1 and 2 only: Given IV Incremental: First dosage: \< 21 years of age: 0.5mg/kg/hr (maximum of 50 mg/hr) for the 1st hour ≥ 21 years of age: 50 mg/hr for the 1st hour. Subsequent dosages: \< 21 years of age: 1.0mg/kg/hr (maximum of 50 mg/hr) for the 1st hour ≥ 21 years of age: 100 mg/hr for the 1st hour. Days 1, 8 and 15.

cyclophosphamide

Intervention Type DRUG

Given IV over 30-60 minutes Dose 600 mg/m2 in 50-250 mL of normal saline (NS) or Dextrose-Water 5%(D5W) (at a maximum concentration of 20 mg/ml) over 30-60 minutes on day 1 of each cycle

methylprednisolone

Intervention Type DRUG

Methylprednisolone 0.8 mg/kg IV over 12 hours on days 1,2,3,4 and 5 of each cycle.

prednisone

Intervention Type DRUG

Dosage 1 mg/kg orally every 12 hours on days 1,2,3,4 and 5 of each cycle. Oral prednisone may be rounded up to the nearest 2.5 mg as necessary for tablet size

Interventions

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rituximab

Cycles 1 and 2 only: Given IV Incremental: First dosage: \< 21 years of age: 0.5mg/kg/hr (maximum of 50 mg/hr) for the 1st hour ≥ 21 years of age: 50 mg/hr for the 1st hour. Subsequent dosages: \< 21 years of age: 1.0mg/kg/hr (maximum of 50 mg/hr) for the 1st hour ≥ 21 years of age: 100 mg/hr for the 1st hour. Days 1, 8 and 15.

Intervention Type BIOLOGICAL

cyclophosphamide

Given IV over 30-60 minutes Dose 600 mg/m2 in 50-250 mL of normal saline (NS) or Dextrose-Water 5%(D5W) (at a maximum concentration of 20 mg/ml) over 30-60 minutes on day 1 of each cycle

Intervention Type DRUG

methylprednisolone

Methylprednisolone 0.8 mg/kg IV over 12 hours on days 1,2,3,4 and 5 of each cycle.

Intervention Type DRUG

prednisone

Dosage 1 mg/kg orally every 12 hours on days 1,2,3,4 and 5 of each cycle. Oral prednisone may be rounded up to the nearest 2.5 mg as necessary for tablet size

Intervention Type DRUG

Other Intervention Names

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IDEC-C2B8 NSC #687451 Cytoxan NSC #26271 Deltaone Meticorten Orasone Liquid Pred Pediapred Sterapred NSC #010023 Deltaone Meticorten Orasone Liquid Pred Pediapred Sterapred NSC #010023

Eligibility Criteria

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Inclusion 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
Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas G. Gross, MD, PhD

Role: STUDY_CHAIR

Nationwide Children's Hospital

Locations

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Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

Birmingham, Alabama, United States

Site Status

Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Southern California Permanente Medical Group

Downey, California, United States

Site Status

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Kaiser Permanente Medical Center - Oakland

Sacramento, California, United States

Site Status

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Stanford Cancer Center

Stanford, California, United States

Site Status

Children's Hospital Center for Cancer and Blood Disorders

Aurora, Colorado, United States

Site Status

Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, United States

Site Status

University of Florida Shands Cancer Center

Gainesville, Florida, United States

Site Status

Nemours Children's Clinic

Jacksonville, Florida, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Site Status

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, United States

Site Status

All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

University of Illinois Cancer Center

Chicago, Illinois, United States

Site Status

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Simmons Cooper Cancer Institute

Springfield, Illinois, United States

Site Status

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Kosair Children's Hospital

Louisville, Kentucky, United States

Site Status

Tulane Cancer Center Office of Clinical Research

Alexandria, Louisiana, United States

Site Status

C.S. Mott Children's Hospital at University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Site Status

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

Site Status

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

University of Mississippi Cancer Clinic

Jackson, Mississippi, United States

Site Status

Ellis Fischel Cancer Center at University of Missouri - Columbia

Columbia, Missouri, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Site Status

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Sunrise Hospital and Medical Center

Las Vegas, Nevada, United States

Site Status

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, United States

Site Status

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, United States

Site Status

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Akron Children's Hospital

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States

Site Status

Legacy Emanuel Hospital and Health Center and Children's Hospital

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

East Tennessee Children's Hospital

Knoxville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Site Status

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Site Status

West Virginia University Health Sciences Center - Charleston

Charleston, West Virginia, United States

Site Status

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States

Site Status

Westmead Institute for Cancer Research at Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Royal Children's Hospital

Brisbane, Queensland, Australia

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, Canada

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Starship Children's Health

Auckland, , New Zealand

Site Status

Christchurch Hospital

Christchurch, , New Zealand

Site Status

Countries

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United States Australia Canada New Zealand

References

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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.

Reference Type RESULT
PMID: 22883417 (View on PubMed)

Other Identifiers

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CDR0000316241

Identifier Type: OTHER

Identifier Source: secondary_id

COG-ANHL0221

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2012-02544

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ANHL0221

Identifier Type: -

Identifier Source: org_study_id

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