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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00066469
First received: August 6, 2003
Last updated: December 3, 2013
Last verified: December 2013
  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 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Event-free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Alive in continuous complete remission with functioning original allograft


Enrollment: 55
Study Start Date: April 2004
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Biological: 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.
Other Names:
  • Rituximab
  • IDEC-C2B8
  • NSC #687451
Drug: 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
Other Names:
  • Cytoxan
  • NSC #26271
Drug: methylprednisolone
Methylprednisolone 0.8 mg/kg IV over 12 hours on days 1,2,3,4 and 5 of each cycle.
Other Names:
  • Deltaone
  • Meticorten
  • Orasone
  • Liquid Pred
  • Pediapred
  • Sterapred
  • NSC #010023
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
Other Names:
  • Deltaone
  • Meticorten
  • Orasone
  • Liquid Pred
  • Pediapred
  • Sterapred
  • NSC #010023

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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 78 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Thomas G. Gross, MD, PhD Nationwide Children's Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00066469     History of Changes
Other Study ID Numbers: ANHL0221, CDR0000316241, COG-ANHL0221, NCI-2012-02544, U10CA098543
Study First Received: August 6, 2003
Results First Received: September 17, 2013
Last Updated: December 3, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
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 hemisuccinate
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

ClinicalTrials.gov processed this record on July 31, 2014