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

University of Nebraska

Status and phase: Completed; Phase 2

Conditions: Neutropenia; Lymphoma

Treatments: Drug: cisplatin; Biological: filgrastim; Drug: cytarabine; Drug: etoposide; Biological: pegfilgrastim; Drug: methylprednisolone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00004192

UCLA-9906080

P30CA036727 (U.S. NIH Grant/Contract)

CWRU-AMGN-1499

NCI-G99-1648

AMGEN-990117

0272-99-FB

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

60 participants in 2 patient groups

Single Dose Filgrastim (SD/01)

Experimental group

Description:

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.

Treatment:

Drug: etoposide

Drug: cytarabine

Drug: methylprednisolone

Drug: cisplatin

Biological: filgrastim

Daily Filgrastim (G-CSF)

Experimental group

Description:

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.

Treatment:

Drug: etoposide

Biological: pegfilgrastim

Drug: cytarabine

Drug: methylprednisolone

Drug: cisplatin