Immunochemotherapy, in Vivo Purging, PBSC Mobilization and Autotransplant in Relapsed or Refractory Follicular Lymphoma

Phase 2

Completed

Conditions: Follicular Lymphoma

Interventions: Procedure: Immunochemotherapy, in vivo purging and autrotransplant

Registration Number: NCT00366275

Lead Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia

Brief Summary: The purpose of this study is to determine the rate and duration of complete remission and molecular response in patients with relapsed/refractory follicular lymphoma, using a combined treatment with rituximab plus chemotherapy followed by in vivo purged peripheral blood stem cells (PBSC) mobilization and autotransplant.

Detailed Description: Autologous stem cell transplantation has been shown effective in the long-term control of follicular lymphoma. Lymphoma, however, can progress after high-dose treatments. Lymphoma cells have been proved to contaminate bone marrow and peripheral blood stem cells (PBSC) collections and may contribute to relapse after autotransplant. The presence in peripheral blood and marrow of PCR-detectable cells bearing the bcl-2 rearrangement appeared to be a surrogate marker of disease and the achievement of a bcl-2 negative status is associated with a lower risk of recurrence. Several methods have been attempted to abolish graft contamination: in vitro treatment with cytotoxic agents, in vitro treatment with anti-B-cell monoclonal antibodies and complement, immunomagnetic beads, positive selection of CD34+ cells. All these techniques usually produce loss of cells, are time-consuming and expensive, and neoplastic depletion is often partial with residual polymerase chain reaction (PCR)-positive cells in the graft.

In the last years the chimeric anti-CD20 monoclonal antibody Rituximab has been shown to be an effective therapeutic option for low-grade lymphoma. Owing to the different mechanism of action, the synergism with cytotoxic agents, and the non-overlapping toxicity, Rituximab is an ideal drug for combination with chemotherapy. On this basis, Rituximab has been used during mobilisation procedures as a tool to obtain in vivo purging and collection of lymphoma-free progenitor cells. In addition, several studies have demonstrated that the efficiency of peripheral blood stem cells (PBSC) harvested is not adversely affected by Rituximab and that engraftment and all parameters of hematopoietic recovery are not compromised. The incorporation of Rituximab into sequential high-dose therapy programs produced high rates of clinical and molecular remission in patients with indolent lymphoma, indicating that the antibody has an additive effect on chemotherapy.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 64

Inclusion Criteria

Patients with relapsed or refractory follicular lymphoma after chemotherapy
Patients with relapsed or refractory follicular lymphoma after rituximab as single agent or with chemotherapy
Patients with transformed follicular lymphoma
CD20-positivity
Age between 18 and 60 years
Advanced Ann Arbor stage
Normal cardiac, renal and hepatic functions
Negativity for human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV)
Total amount of anthracycline previously received < 300 mg/m^2

Exclusion criteria:

Creatinine > 2 mg/dl
Alanine transaminase (ALT) and alkaline phosphatase > 2N
Cardiac or pulmonary disease
Severe organic or psychiatric disease
Positivity for human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV)
Pregnancy, breastfeeding
Cancer diagnosis in the 5 years before lymphoma diagnosis, except of non-melanoma skin cancer and Cervical Intraepithelial Neoplasia (CIN)

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
In vivo purging autotransplant	Immunochemotherapy, in vivo purging and autrotransplant	-

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	every 3 months for the first year after autotransplant and every 6 months after the first year of follow up	PFS is calculated according to the Kaplan-Meier estimator. The observation time of each subject is defined as the time from entry into the study until lymphoma progression or death as a result of any cause whichever occurs first. The 5-year PFS is the estimated cumulative probability of surviving at least 5 years without progression.

Secondary Outcome Measures