AzTrials
AzTrials

Lymphoproliferative DisorderPhase 2NCT00066469

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

A Phase 2 study testing rituximab, cyclophosphamide and methylprednisolone in people with Lymphoproliferative Disorder, run by Children's Oncology Group at 78 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages Up to 30 years
Conditions the study is for
Lymphoproliferative Disorder
What is being tested?
rituximab, cyclophosphamide and methylprednisolone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
78 sitesin 4 countries
Study dates
Apr 2004to 31 Dec 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

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

Trial locations and contacts

78 sites in 4 countries.

78 sites in 4 countries

United States66 sites

  • Akron Children's Hospital

    Akron, Ohio, 44308-1062

  • Tulane Cancer Center Office of Clinical Research

    Alexandria, Louisiana, 71315-3198

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

    Ann Arbor, Michigan, 48109-0286

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • Children's Hospital Center for Cancer and Blood Disorders

    Aurora, Colorado, 80045

  • Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

    Birmingham, Alabama, 35294

  • Fletcher Allen Health Care - University Health Center Campus

    Burlington, Vermont, 05401

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

    Chapel Hill, North Carolina, 27599-7295

  • West Virginia University Health Sciences Center - Charleston

    Charleston, West Virginia, 25302

  • Blumenthal Cancer Center at Carolinas Medical Center

    Charlotte, North Carolina, 28232-2861

  • University of Illinois Cancer Center

    Chicago, Illinois, 60612-7243

  • Children's Memorial Hospital - Chicago

    Chicago, Illinois, 60614

  • University of Chicago Cancer Research Center

    Chicago, Illinois, 60637-1470

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3039

  • Rainbow Babies and Children's Hospital

    Cleveland, Ohio, 44106-5000

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

  • Ellis Fischel Cancer Center at University of Missouri - Columbia

    Columbia, Missouri, 65203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205-2696

  • Driscoll Children's Hospital

    Corpus Christi, Texas, 78411

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201-1379

  • Southern California Permanente Medical Group

    Downey, California, 90242-2814

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042-3300

  • Lee Cancer Care of Lee Memorial Health System

    Fort Myers, Florida, 33901

  • University of Florida Shands Cancer Center

    Gainesville, Florida, 32610-0232

  • Butterworth Hospital at Spectrum Health

    Grand Rapids, Michigan, 49503-2560

  • Hackensack University Medical Center Cancer Center

    Hackensack, New Jersey, 07601

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202-5289

  • University of Mississippi Cancer Clinic

    Jackson, Mississippi, 39216-4505

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207

  • CCOP - Kalamazoo

    Kalamazoo, Michigan, 49007-5341

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • East Tennessee Children's Hospital

    Knoxville, Tennessee, 37901

  • Sunrise Hospital and Medical Center

    Las Vegas, Nevada, 89109-2306

  • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Loma Linda University Cancer Institute at Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Kosair Children's Hospital

    Louisville, Kentucky, 40232

  • Marshfield Clinic - Marshfield Center

    Marshfield, Wisconsin, 54449

  • University of Miami Sylvester Comprehensive Cancer Center - Miami

    Miami, Florida, 33136

  • Masonic Cancer Center at University of Minnesota

    Minneapolis, Minnesota, 55455

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232-6838

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

    New York, New York, 10032

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507-1971

  • Oklahoma University Cancer Institute

    Oklahoma City, Oklahoma, 73104

  • UNMC Eppley Cancer Center at the University of Nebraska Medical Center

    Omaha, Nebraska, 68198-6805

  • Sacred Heart Cancer Center at Sacred Heart Hospital

    Pensacola, Florida, 32504

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104-9786

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016-7710

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Legacy Emanuel Hospital and Health Center and Children's Hospital

    Portland, Oregon, 97227

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

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

    Rochester, New York, 14642

  • Kaiser Permanente Medical Center - Oakland

    Sacramento, California, 95825

  • Primary Children's Medical Center

    Salt Lake City, Utah, 84113-1100

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78207

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229-3993

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

  • Children's Hospital and Regional Medical Center - Seattle

    Seattle, Washington, 98105

  • Simmons Cooper Cancer Institute

    Springfield, Illinois, 62794-9677

  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    St Louis, Missouri, 63110

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • Stanford Cancer Center

    Stanford, California, 94305-5824

  • SUNY Upstate Medical University Hospital

    Syracuse, New York, 13210

  • New York Medical College

    Valhalla, New York, 10595

  • Alfred I. duPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

Canada7 sites

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 1Z2

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • Montreal Children's Hospital at McGill University Health Center

    Montreal, Quebec, H3H 1P3

  • Hopital Sainte Justine

    Montreal, Quebec, H3T 1C5

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • Children's & Women's Hospital of British Columbia

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Australia3 sites

  • Royal Children's Hospital

    Brisbane, Queensland, 4029

  • Princess Margaret Hospital for Children

    Perth, Western Australia, 6001

  • Westmead Institute for Cancer Research at Westmead Hospital

    Westmead, New South Wales, 2145

Other trials in Australia

New Zealand2 sites

  • Starship Children's Health

    Auckland, 1

  • Christchurch Hospital

    Christchurch

Other trials in New Zealand

About this study

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)

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.

Read the 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.

Keywords
post-transplant lymphoproliferative disorder
Medical subject headings
Lymphoproliferative Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rituximabBiological

    Also called IDEC-C2B8, NSC #687451

    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.

  • cyclophosphamideDrug

    Also called Cytoxan, NSC #26271

    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

  • methylprednisoloneDrug

    Also called Deltaone, Meticorten, Orasone, Liquid Pred

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

  • prednisoneDrug

    Also called Deltaone, Meticorten, Orasone, Liquid Pred

    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

Study groups in NCT00066469
Study groupRoleWhat they receive
Cyclophosphamide, prednisone, rituximabExperimentalPatients 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
Receives: Biological: rituximab; Drug: cyclophosphamide; Drug: methylprednisolone; Drug: prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2003 (estimated)
  2. Study startApr 2004
  3. Primary completion1 Oct 2009
  4. Study completion31 Dec 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00066469
Sponsor's protocol ID
ANHL0221
Other IDs
CDR0000316241, COG-ANHL0221, NCI-2012-02544, U10CA098543
Status last verified
Sep 2016
First submitted
6 Aug 2003
Last updated
6 Aug 2019
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 22883417

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing rituximab, cyclophosphamide and methylprednisolone in people with Lymphoproliferative Disorder, run by Children's Oncology Group at 78 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 78 sites in United States, Canada, Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free Survival (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00066469, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in