Fludeoxyglucose F 18 Positron Emission Tomography in Predicting Risk of Relapse in Patients With Non-Hodgkin's Lymphoma Who Are Undergoing Combination Chemotherapy With or Without Autologous Stem Cell or Bone Marrow Transplant

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00238368
First received: October 12, 2005
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Giving chemotherapy with an autologous stem cell or bone marrow transplant may allow more chemotherapy to be given so that more cancer cells are killed. Procedures, such as fludeoxyglucose F 18 positron emission tomography (FDG-PET) (done during chemotherapy) may help doctors predict a patient's risk of relapse and help plan the best treatment.

PURPOSE: This phase II trial is studying how well FDG-PET works in predicting risk of relapse in patients with aggressive non-Hodgkin's lymphoma who are undergoing combination chemotherapy with or without autologous stem cell or bone marrow transplant.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Biological: rituximab
Drug: busulfan
Drug: cisplatin
Drug: cyclophosphamide
Drug: cytarabine
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: methylprednisolone
Drug: prednisone
Drug: vincristine sulfate
Procedure: autologous bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Procedure: positron emission tomography
Radiation: fludeoxyglucose F 18
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Diagnostic
Official Title: Autologous Blood or Marrow Transplantation for Aggressive Non-Hodgkin's Lymphoma Based on Early [18F] FDG-PET Scanning

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • 2-year event free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Predictive value of early negative fludeoxyglucose F 18 positron emission tomography (FDG-PET) [ Designated as safety issue: No ]
  • Correlation of International Prognostic Index risk category with FDG-PET results and overall outcome [ Designated as safety issue: No ]

Enrollment: 59
Study Start Date: February 2004
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine event-free survival of patients with aggressive non-Hodgkin's lymphoma treated with early high-dose therapy and autologous peripheral blood stem cell (PBSC) or bone marrow transplantation (BMT) based on positive fludeoxyglucose F 18 positron emission tomography (FDG-PET) results obtained during first-line chemotherapy.
  • Compare event-free survival of patients treated with this regimen with historical event-free survival of patients with positive FDG-PET results obtained during first-line chemotherapy that are not treated with early high-dose therapy.

Secondary

  • Compare overall survival of patients treated with a standard treatment regimen vs early high-dose therapy and autologous PBSC or BMT based on FDG-PET results obtained during first-line chemotherapy.
  • Determine the predictive value of an early negative FDG-PET result in these patients.
  • Correlate International Prognostic Index risk category with FDG-PET results and overall outcome in these patients.

OUTLINE: This is a pilot study.

  • First-line chemotherapy: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1, oral prednisone on days 1-5, and rituximab IV on day 1 (patients with CD20-positive disease only) OR another standard first-line chemotherapy regimen. Treatment repeats every 14-21 days for 2 or 3 courses in the absence of disease progression or unacceptable toxicity.
  • Radiographic staging: Between days 11-20 of course 2 or 3 OR days 11-13 of course 3 of first-line chemotherapy, patients receive fludeoxyglucose F 18 (FDG) IV. One hour later, patients undergo whole-body FDG-positron emission tomography (PET) and CT scan. Patients with no evidence of malignant disease by FDG-PET (i.e., negative result) receive a standard treatment regimen that may include localized radiotherapy for limited stage or bulky disease followed, 4-6 weeks later, by a repeat whole-body FDG-PET and CT scan. Patients with progressive disease after first-line chemotherapy are removed from the study. Patients with evidence of malignant disease by FDG-PET (i.e., positive result) and stable disease or better proceed to ESHAP chemotherapy.
  • ESHAP chemotherapy: Patients receive etoposide IV over 2 hours, methylprednisolone IV, and cisplatin IV over 3 hours on days 1-4 followed by cytarabine IV over 2 hours on day 5. Patients with CD20-positive disease also receive rituximab IV on day 1. Treatment repeats every 14-21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 day after completion of course 2, patients receive filgrastim (G-CSF) subcutaneously once daily followed by leukapheresis to collect peripheral blood stem cells (PBSC). Some patients may also undergo bone marrow (BM) harvest if sufficient PBSC are not collected. Patients with a sufficient number of stem cells proceed to high-dose therapy and autologous PBSC transplantation (PBSCT) or BM transplantation (BMT).
  • High-dose therapy and PBSCT or BMT: No more than 4 weeks after completion of PBSC collection or BM harvest, patients receive high-dose therapy that may include cyclophosphamide and total-body irradiation OR busulfan and cyclophosphamide. Patients then undergo PBSCT or BMT. Between 4-6 weeks after completion of PBSCT or BMT, patients undergo repeat whole-body FDG-PET and CT scan. Patients may also undergo consolidative radiotherapy to the sites of bulky disease at the discretion of the physician.

After completion of study treatment, patients are followed at 4 weeks, every 3 months for 2 years, every 6 months for 1 year, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study within 18 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed aggressive non-Hodgkin's lymphoma of 1 of the following subtypes:

    • Diffuse large B-cell lymphoma
    • Mediastinal (thymic) B-cell lymphoma
    • Grade 3 follicular lymphoma
    • Anaplastic large cell lymphoma
    • Peripheral T-cell lymphoma
  • Must have adequate staging of disease by the following techniques:

    • CT scan or MRI of affected sites
    • Bone marrow biopsy (in cases where results influence the duration of chemotherapy only)
    • Lumbar puncture (if clinically indicated)
  • Stage I-IV disease
  • Any International Prognostic Index risk category
  • Radiographically measurable disease
  • None of the following aggressive non-Hodgkin's subtypes are allowed:

    • Mantle cell lymphoma
    • Lymphoblastic lymphoma
    • Burkitt's lymphoma
    • Mycosis fungoides/Sezary's syndrome
    • HTLV-1-associated T-cell leukemia/lymphoma
    • Primary CNS lymphoma
    • HIV-associated lymphoma
    • Transformed lymphomas
  • No prior diagnosis of another hematologic malignancy
  • No known progressive disease during prior first-line chemotherapy
  • No active CNS involvement by lymphoma, except CNS involvement at diagnosis that is previously treated and in remission

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-4 (0-2 for peripheral blood stem cell [PBSC] or bone marrow transplantation [BMT] patients)

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count > 1,000/mm^3*
  • Platelet count ≥ 75,000/mm^3 NOTE: *PBSC or BMT patients only

Hepatic

  • Bilirubin ≤ 2.0 mg/dL unless due to Gilbert's disease or lymphoma*
  • No known significant hepatic dysfunction that is not expected to improve and would preclude PBSC or BMT NOTE: *PBSC or BMT patients only

Renal

  • Creatinine ≤ 2.0 mg/dL*
  • No known significant renal dysfunction that is not expected to improve and would preclude PBSC or BMT NOTE: *PBSC or BMT patients only

Cardiovascular

  • Ejection fraction ≥ 45% by echocardiogram or MUGA*
  • No known significant cardiac dysfunction that is not expected to improve and would preclude PBSC or BMT NOTE: *PBSC or BMT patients only; a cardiology consult and evaluation may override ejection fraction criterion

Pulmonary

  • FEV_1 and FVC ≥ 50% of predicted for patients who have not received thoracic or mantle radiotherapy (75% of predicted for patients who have received thoracic or mantle radiotherapy)*
  • No known significant pulmonary dysfunction that is not expected to improve and would preclude PBSC or BMT NOTE: *PBSC or BMT patients only

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other malignancy within the past 3 years except carcinoma in situ of the cervix or nonmelanoma skin cancer
  • No known HIV positivity OR HIV negative (for PBSC or BMT patients only)
  • No serious illness that would preclude study participation
  • No contraindication to autologous BMT

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • See Disease Characteristics
  • No more than 3 prior courses of chemotherapy for lymphoma

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified
  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: NCT00238368

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: Lode J. Swinnen, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00238368     History of Changes
Other Study ID Numbers: J0348 CDR0000445618, P30CA006973, JHOC-J0348, JHOC-03082605
Study First Received: October 12, 2005
Last Updated: April 16, 2014
Health Authority: United States: Federal Government

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage I adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage I grade 3 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 3 follicular lymphoma
anaplastic large cell lymphoma
stage I adult T-cell leukemia/lymphoma
stage II adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Busulfan
Cyclophosphamide
Cytarabine
Rituximab
Cisplatin
Doxorubicin
Etoposide
Methylprednisolone Hemisuccinate
Prednisolone
Prednisone
Vincristine
Lenograstim
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on July 28, 2014