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

NCT00066469 | Completed Phase 2 Results DMC

• 5 other identifiers: ANHL0221CDR0000316241COG-ANHL0221NCI-2012-02544U10CA098543
• Study Type: interventional
• Target: 55
• Locations: 4 countries
• Sites: 78

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.

Conditions

Lymphoproliferative Disorder

Keywords

post-transplant lymphoproliferative disorder

Outcome Measures

Primary Outcomes (1)

• Event-free Survival

  Alive in continuous complete remission with functioning original allograft. The Event Free Survival (EFS) will be estimated by the Kaplan-Meier method.

  2 years

Study Arms (1)

Cyclophosphamide, prednisone, rituximab

EXPERIMENTAL

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

Biological: rituximab; Drug: cyclophosphamide; Drug: methylprednisolone; Drug: prednisone

Interventions

rituximab 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.

Also known as: IDEC-C2B8, NSC #687451

Cyclophosphamide, prednisone, rituximab

cyclophosphamide 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

Also known as: Cytoxan, NSC #26271

Cyclophosphamide, prednisone, rituximab

methylprednisolone DRUG

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

Also known as: Deltaone, Meticorten, Orasone, Liquid Pred, Pediapred, Sterapred, NSC #010023

Cyclophosphamide, prednisone, rituximab

prednisone 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

Also known as: Deltaone, Meticorten, Orasone, Liquid Pred, Pediapred, Sterapred, NSC #010023

Cyclophosphamide, prednisone, rituximab

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (78)

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

Birmingham, Alabama, 35294, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016-7710, United States

Location

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Southern California Permanente Medical Group

Downey, California, 90242-2814, United States

Location

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Kaiser Permanente Medical Center - Oakland

Sacramento, California, 95825, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Stanford Cancer Center

Stanford, California, 94305-5824, United States

Location

Children's Hospital Center for Cancer and Blood Disorders

Aurora, Colorado, 80045, United States

Location

Alfred I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, 33901, United States

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610-0232, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, 33136, United States

Location

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, 32504, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612-7243, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

Simmons Cooper Cancer Institute

Springfield, Illinois, 62794-9677, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40232, United States

Location

Tulane Cancer Center Office of Clinical Research

Alexandria, Louisiana, 71315-3198, United States

Location

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

Ann Arbor, Michigan, 48109-0286, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, 49503-2560, United States

Location

CCOP - Kalamazoo

Kalamazoo, Michigan, 49007-5341, United States

Location

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Cancer Clinic

Jackson, Mississippi, 39216-4505, United States

Location

Ellis Fischel Cancer Center at University of Missouri - Columbia

Columbia, Missouri, 65203, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, 68198-6805, United States

Location

Sunrise Hospital and Medical Center

Las Vegas, Nevada, 89109-2306, United States

Location

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, 10032, United States

Location

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

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

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

Chapel Hill, North Carolina, 27599-7295, United States

Location

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, 28232-2861, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308-1062, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106-5000, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205-2696, United States

Location

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, 73104, United States

Location

Legacy Emanuel Hospital and Health Center and Children's Hospital

Portland, Oregon, 97227, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-9786, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

East Tennessee Children's Hospital

Knoxville, Tennessee, 37901, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

Driscoll Children's Hospital

Corpus Christi, Texas, 78411, United States

Location

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78207, United States

Location

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229-3993, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113-1100, United States

Location

Fletcher Allen Health Care - University Health Center Campus

Burlington, Vermont, 05401, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042-3300, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507-1971, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

West Virginia University Health Sciences Center - Charleston

Charleston, West Virginia, 25302, United States

Location

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, 54449, United States

Location

Westmead Institute for Cancer Research at Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Children's Hospital

Brisbane, Queensland, 4029, Australia

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 1Z2, Canada

Location

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, V6H 3V4, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, H3H 1P3, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Starship Children's Health

Auckland, 1, New Zealand

Location

Christchurch Hospital

Christchurch, New Zealand

Location

Related Publications (1)

• 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.

  PMID: 22883417 RESULT

MeSH Terms

Conditions

Lymphoproliferative Disorders

Interventions

Rituximab; Cyclophosphamide; Methylprednisolone; Prednisone; prednisolone phosphate

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

352-273-0558

Study Officials

• Thomas G. Gross, MD, PhD

  Nationwide Children's Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2003
• First Posted: August 7, 2003
• Study Start: April 1, 2004
• Primary Completion: October 1, 2009
• Study Completion: December 31, 2013
• Last Updated: August 6, 2019
• Results First Posted: January 17, 2014

Record last verified: 2016-09

Locations

US (66); NZ (2); AU (3); CA (7)