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

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00066469

Purpose

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.

Condition	Intervention	Phase
Lymphoproliferative Disorder	Biological: rituximab Drug: cyclophosphamide Drug: methylprednisolone Drug: prednisone	Phase II

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Study of the Combination of Cyclophosphamide, Prednisone and Rituximab (CPR) in Children, Adolescents and Young Adults With CD20 Positive Post-Transplant Lymphoproliferative Disease (PTLD) Following Solid Organ Transplantation (SOT)

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Cyclophosphamide Prednisolone Prednisolone acetate Prednisone Depo-medrol Medrol veriderm Methylprednisolone Rituximab Prednisolone sodium phosphate Prednisolone Sodium Succinate Methylprednisolone Sodium Succinate Methylprednisolone hemisuccinate 6-Methylprednisolone

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Event-free survival at 2 years [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	April 2004
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

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

Ages Eligible for Study:	up to 30 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00066469

Show 78 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Thomas G. Gross, MD, PhD

Nationwide Children's Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Gregory H. Reaman, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier:	NCT00066469 History of Changes
Other Study ID Numbers:	CDR0000316241, COG-ANHL0221
Study First Received:	August 6, 2003
Last Updated:	November 20, 2010
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

post-transplant lymphoproliferative disorder

Additional relevant MeSH terms:

Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Methylprednisolone Hemisuccinate
Prednisolone
Prednisone
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors

Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on February 09, 2012