Colony-Stimulating Factors to Relieve Neutropenia in Patients With Recurrent Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Colony-stimulating factors may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. PURPOSE: Randomized phase II trial to compare the effectiveness of filgrastim-SD/01 with that of filgrastim to relieve the neutropenia following combination chemotherapy in patients who have non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: I. Compare the effect of single dose filgrastim-SD/01 vs daily filgrastim (G-CSF) on the duration of neutropenia in course 1 after combination chemotherapy in patients with recurrent non-Hodgkin's lymphoma. II. Compare the effect of these regimens on duration of neutropenia in courses 2-4, absolute neutrophil counts (ANC) in courses 1-4, time to ANC recovery in courses 1-4, and safety in these patients. III. Determine the pharmacokinetic profile of these drugs in course 1 in these patients. OUTLINE: This is a randomized, open label, multicenter study. Patients are randomized to one of two treatment arms. All patients receive etoposide IV over 1 hour on days 1-4, cisplatin IV continuously on days 1-4, methylprednisolone IV over 15 minutes on days 1-5, and cytarabine IV over 2 hours on day 5. Treatment is repeated every 21 days for up to 4 courses. Arm I: Patients receive filgrastim-SD/01 subcutaneously (SQ) on day 6. Arm II: Patients receive filgrastim (G-CSF) SQ daily beginning on day 6 and continuing for 12 days or until blood counts recover. PROJECTED ACCRUAL: A total of 60 patients (30 per arm) will be accrued for this study within at least 6 months.

Official Title
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A Randomized, Multicenter, Open-Label Study of Single Dose Filgrastim-SD/01 Versus Daily Filgrastim Following ESHAP Chemotherapy for Non-Hodgkin's Lymphoma

Conditions
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Lymphoma, Neutropenia

Intervention / Treatment
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* Biological: filgrastim
* Biological: pegfilgrastim
* Drug: cisplatin
* Drug: cytarabine
* Drug: etoposide
* Drug: methylprednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of non-Hodgkin's lymphoma (NHL) o Relapsed disease or Refractory to first line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy Age 18 and over ECOG 0-2Absolute neutrophil count at least 1,500/mm3Platelet count at least 150,000/mm3 Creatinine not greater than 1.5 mg/dL or Creatinine clearance greater than 60 mL/min Fertile patients must use effective barrier contraception At least 4 weeks since prior radiotherapy At least 72 hours since prior antimicrobials At least 30 days since other prior investigational drug Exclusion Criteria: No myelodysplastic syndrome or chronic myeloid leukemia Not pregnant or nursing/Negative pregnancy test No other prior malignancy except Curatively treated basal cell or squamous cell carcinoma Carcinoma in situ of the cervix Surgically cured malignancy No hypersensitivity to E. coli derived products (e.g., filgrastim (G-CSF), insulin, asparaginase) No prior bone marrow or peripheral blood stem cell (PBSC) transplantation for NHL No prior filgrastim-SD/01 No other concurrent myelopoietic growth factors No concurrent WBC transfusions No concurrent PBSC collection No more than 2 prior courses of chemotherapy for any malignancy No concurrent corticosteroids except topical steroids or as pre-medications or associated with chemotherapy No other concurrent investigational drug No concurrent prophylactic antibiotics during course 1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized, open label, multicenter study. Patients are randomized to one of two treatment arms. All patients receive etoposide IV over 1 hour on days 1-4, cisplatin IV continuously on days 1-4, methylprednisolone IV over 15 minutes on days 1-5, and cytarabine IV over 2 hours on day 5. Treatment is repeated every 21 days for up to 4 courses. Arm I: Patients receive filgrastim-SD/01 subcutaneously (SQ) on day 6. Arm II: Patients receive filgrastim (G-CSF) SQ daily beginning on day 6 and continuing for 12 days or until blood counts recover.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Dose Filgrastim (SD/01)<br>Participants receive etoposide IV over 1 hour on days 1-4, cisplatin IV continuously on days 1-4, methylprednisolone IV over 15 minutes on days 1-5, and cytarabine IV over 2 hours on day 5. Treatment is repeated every 21 days for up to 4 courses. Arm I: Participants receive filgrastim-SD/01 subcutaneously (SQ) on day 6. | Biological: filgrastim<br> <br> * Other names: Neupogen;Drug: cisplatin<br> <br> * Other names: chemotherapy drug;Drug: cytarabine<br> <br> * Other names: cytosine arabinoside;Drug: etoposide<br> <br> * Other names: Etopophos, Toposar;Drug: methylprednisolone<br> <br> * Other names: Depo-Medrol, Medrol, Solu-Medrol, P-Care D80, ReadySharp Methylprednisolone, and P-Care D40;|
| Experimental: Daily Filgrastim (G-CSF)<br>Participants receive etoposide IV over 1 hour on days 1-4, cisplatin IV continuously on days 1-4, methylprednisolone IV over 15 minutes on days 1-5, and cytarabine IV over 2 hours on day 5. Treatment is repeated every 21 days for up to 4 courses. Arm II: Participants receive filgrastim (G-CSF) SQ daily beginning on day 6 and continuing for 12 days or until blood counts recover. | Biological: pegfilgrastim<br> <br> * Other names: Neulasta;Drug: cisplatin<br> <br> * Other names: chemotherapy drug;Drug: cytarabine<br> <br> * Other names: cytosine arabinoside;Drug: etoposide<br> <br> * Other names: Etopophos, Toposar;Drug: methylprednisolone<br> <br> * Other names: Depo-Medrol, Medrol, Solu-Medrol, P-Care D80, ReadySharp Methylprednisolone, and P-Care D40;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neutropenia, Waldenstrom macroglobulinemia, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma