High-Dose Therapy Treatment in Patients With Follicular Lymphoma

French Innovative Leukemia Organisation

Status and phase: Completed; Phase 3

Conditions: Follicular Lymphoma

Treatments: Procedure: high dose therapy and autologous stem cell transplantation; Procedure: chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT00696735

GOELAMS 064

Details and patient eligibility

About

Follicular lymphomas are a subgroup of B-cell non-Hodgkin lymphomas, accounting for 15% to 30% of newly diagnosed lymphomas.1-3 Median survival varies from 5 to 10 years depending on the prognostic factors at diagnosis and response to first-line therapy.4-6 Whatever the treatment, no plateau appears on survival curves, and virtually all patients relapse; follicular lymphomas are ultimately progressive, and fatal.2,3,5 No reference first-line treatment is clearly defined. One of the most active therapies is still doxorubicin-based chemotherapy with or without interferon.7-9 New therapeutic approaches including purine analogs and anti-CD20 monoclonal antibody are promising and are progressively included in the management of these lymphomas.2,3,10-13 The role of high-dose therapy (HDT) as a salvage treatment for patients with relapsing follicular lymphoma is demonstrated by some authors; several reports have shown the superiority of HDT followed by autologous stem-cell transplantation, purged or unpurged, compared with conventional chemotherapy in terms of no relapse and overall survival.14-18 Only a few reports have been published showing HDT results as a first-line treatment for poor-risk patients with follicular lymphoma, and the results remain controversial.19-26 These data prompted the French Groupe Ouest-Est des Leucémies et Autres Maladies du Sang (GOELAMS) to conduct a prospective randomized trial using patients with newly diagnosed follicular lymphoma with a high tumor burden. A combined doxorubicin-based chemotherapy associated with interferon was compared to front-line HDT followed by purged autologous stem-cell transplantation.

Full description

Age 8-60 years old follicular lymphoma Not previously treated Stage II bulky, III or IV An Arbor classification high tumor burden

Enrollment: 172 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 18-60 years old
• Follicular Lymphoma B, C or D (Working Formulation)
• No previous treatment
• Seronegativity HIV
• ECOG performance status less than or 2
• eligible for autologous stem-cell transplantation
• Stage II , III or IV Ann Arbor Classification
• criterias of high tumor burden
• Patient's written informed consent

Exclusion criteria

• Age less than 18 years old or more than 60 years old
• Other type of lymphoma
• Stage less than 3 or III-IV (faible masse)
• Seropositivity HIV
• Patients with a history of another malignancy except basal cell skin cancer or in situ uterus cancer

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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172 participants in 2 patient groups

1

Active Comparator group

Description:

standard chemotherapy arm, the CHVP (cyclophosphamide, low-dose doxorubicin, teniposide, and prednisone) regimen consisted of cyclophosphamide (600 mg/m2), doxorubicin (25 mg/m2), and teniposide (60 mg/m2), all administered intravenously on day 1, and prednisone (40 mg/m2), administered orally on days 1 to 5.4,12 Treatment consisted of a 6-course induction phase administered monthly, followed, for responders and patients presenting a stable disease, by a maintenance phase that consisted of 1 cycle every 2 months for 1 year. Concomitant subcutaneous interferon alfa-2b was administered at 5 x 106 3 times a week for 18 months.

Treatment:

Procedure: chemotherapy

2

Experimental group

Description:

VCAP (cyclophosphamide, high-dose doxorubicin, prednisone, and vincristine) regimen as a first-line therapy combining vindesine (3 mg/m2) on day 1, cyclophosphamide (1500 mg/m2) on day 2, doxorubicin (80 mg/m2) on day 2, and prednisolone (50 mg/m2) on days 1 to 5, every 3 weeks.19,31,32 Patients in CR, VGPR, or PR after the second or third VCAP cycle continued on to stem-cell harvesting and received, before transplantation, one course of IMVP16 (ifosfamide, methotrexate, and VP-16), which combined ifosfamide (1.5 g/m2) and VP16 (100 mg/m2) on days 1 through 3, and methotrexate (30 mg/m2) on days 1 and 10. Patients with less than PR after the VCAP cycles received, as salvage therapy, 2 to 3 courses of DHAP (dexamethasone, high-dose cytarabine, and cisplatin) combining cisplatine (100 mg/m2) on day 1, cytarabine (4 g/m2) on day 2, and dexamethasone (40 mg/m2) on days 1 through 4. If at least a PR was obtained after DHAP, stem cells were harvested or patients were considered as failures

Treatment:

Procedure: high dose therapy and autologous stem cell transplantation