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

Johns Hopkins Medicine

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Treatments

Drug: prednisone

Drug: vincristine sulfate

Biological: rituximab

Radiation: radiation therapy

Drug: methylprednisolone

Procedure: autologous bone marrow transplantation

Drug: cytarabine

Drug: cisplatin

Radiation: fludeoxyglucose F 18

Drug: busulfan

Drug: doxorubicin hydrochloride

Drug: etoposide

Procedure: peripheral blood stem cell transplantation

Procedure: positron emission tomography

Drug: cyclophosphamide

Biological: filgrastim

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00238368

J0348 CDR0000445618

P30CA006973 (U.S. NIH Grant/Contract)

JHOC-J0348

JHOC-03082605

Details and patient eligibility

About

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.

Full 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.

Enrollment

59 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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