High-Dose Therapy Treatment in Patients With Follicular Lymphoma
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Age 8-60 years old follicular lymphoma Not previously treated Stage II bulky, III or IV An Arbor classification high tumor burden
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 1 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. |
Procedure: chemotherapy
injection cyclophosphamide doxorubicin (25 mg/m2), and teniposide (60 mg/m2)(600 mg/m2)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.
|
| Experimental: 2 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 |
Procedure: high dose therapy and autologous stem cell transplantation
VCAP regimen 3 cycles , less than PR: 2-3 DHAP, stem cell collection, in vitro purging autologous stem cell transplantation with TBI and cyclophosphamide
|
Outcome Measures
Primary Outcome Measures
- event free survival [from diagnosis to first event]
Secondary Outcome Measures
- safety [from diagnosis to death]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 18-60 years old
-
Follicular Lymphoma B, C or D (Working Formulation)
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No previous treatment
-
Seronegativity HIV
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ECOG performance status less than or 2
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eligible for autologous stem-cell transplantation
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Stage II , III or IV Ann Arbor Classification
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criterias of high tumor burden
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Patient's written informed consent
Exclusion Criteria:
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Age less than 18 years old or more than 60 years old
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Other type of lymphoma
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Stage less than 3 or III-IV (faible masse)
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Seropositivity HIV
-
Patients with a history of another malignancy except basal cell skin cancer or in situ uterus cancer
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Emmanuel GYAN | Tours | France | 37000 | |
| 2 | Philippe COLOMBAT | Tours | France | 37000 |
Sponsors and Collaborators
- French Innovative Leukemia Organisation
Investigators
- Principal Investigator: Philippe COLOMBAT, MD PHD, French Innovative Leukemia Organisation
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GOELAMS 064