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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00066469




Registration number
NCT00066469
Ethics application status
Date submitted
6/08/2003
Date registered
7/08/2003
Date last updated
6/08/2019

Titles & IDs
Public title
Cyclophosphamide, Rituximab, and Either Prednisone or Methylprednisolone in Treating Patients With Lymphoproliferative Disease After Solid Organ Transplantation
Scientific 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)
Secondary ID [1] 0 0
CDR0000316241
Secondary ID [2] 0 0
ANHL0221
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoproliferative Disorder 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - rituximab
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - methylprednisolone
Treatment: Drugs - prednisone

Experimental: 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


Treatment: Other: 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.

Treatment: Drugs: 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

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

Treatment: Drugs: 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 code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free Survival
Timepoint [1] 0 0
2 years

Eligibility
Key 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
Minimum age
No limit
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2004
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/12/2013
Sample size
Target
Accrual to date
Final
55
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Westmead Institute for Cancer Research at Westmead Hospital - Westmead
Recruitment hospital [2] 0 0
Royal Children's Hospital - Brisbane
Recruitment hospital [3] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4029 - Brisbane
Recruitment postcode(s) [3] 0 0
6001 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Delaware
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Florida
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Georgia
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Illinois
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Indiana
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Kentucky
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Louisiana
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Michigan
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Minnesota
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Mississippi
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Missouri
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Nebraska
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Nevada
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New Jersey
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Tennessee
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Texas
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Utah
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Vermont
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Virginia
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Washington
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West Virginia
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Wisconsin
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Canada
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Alberta
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Canada
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British Columbia
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Manitoba
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Nova Scotia
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Ontario
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Canada
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Quebec
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New Zealand
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Auckland
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New Zealand
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Christchurch

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00066469
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Thomas G. Gross, MD, PhD
Address 0 0
Nationwide Children's Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00066469