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

Follicular Lymphoma Clinical Trial

Official title:

Phase II of Immunochemotherapy, in Vivo Purging, PBSC Mobilization and Autotransplant in Patients With Relapsed or Refractory Follicular Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00366275
• Other study ID #: ML17165
• Secondary ID: LNH 1-02
• Status: Completed
• Phase: Phase 2
• First received: August 17, 2006
• Last updated: October 26, 2012
• Start date: January 2002
• Est. completion date: September 2007

Study information

• Verified date: October 2012
• Source: IRCCS Policlinico S. Matteo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: September 2007
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

Procedure:
• Immunochemotherapy, in vivo purging and autrotransplant
2-4 courses every 3 weeks with rituximab 375 mg/m^2 on day 1, vincristine 1.4 mg/m^2 on day 2 and cyclophosphamide 400 mg/m^2 on days 2-6. Courses were started if granulocytes >1.5 · 10^9/l. The phase of peripheral blood stem cells (PBSC) mobilization coupled rituximab 375 mg/m^2 on days 1 and 9 with high-dose cytarabine (AraC) 2 g/m^2 every 12 hours on days 2 and 3. Granulocyte colony-stimulating factor (G-CSF)(5 mcg/kg/day subcutaneously) was administered from day 6. High-dose chemotherapy with autotransplant consisted of BEAM [carmustine (BCNU), etoposide, Cytarabine (AraC), melphalan] followed by the infusion of in vivo purged peripheral blood stem cells (PBSC) + 2 consolidation doses of rituximab 375 mg/m^2 on days +14 and +21 after autotransplant.

Locations

Country	Name	City	State
Italy	Division of Hematology, IRCCS Policlinico S. Matteo, University of Pavia	Pavia

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Policlinico S. Matteo

Country where clinical trial is conducted

Italy, 

References & Publications (3)

Arcaini L, Montanari F, Alessandrino EP, Tucci A, Brusamolino E, Gargantini L, Cairoli R, Bernasconi P, Passamonti F, Bonfichi M, Zoli V, Bottelli C, Calatroni S, Troletti D, Merli M, Pascutto C, Majolino I, Rossi G, Morra E, Lazzarino M. Immunochemothera — View Citation

Arcaini L, Orlandi E, Alessandrino EP, Iacona I, Brusamolino E, Bonfichi M, Bernasconi P, Calatroni S, Tenore A, Montanari F, Troletti D, Pascutto C, Regazzi M, Lazzarino M. A model of in vivo purging with Rituximab and high-dose AraC in follicular and mantle cell lymphoma. Bone Marrow Transplant. 2004 Jul;34(2):175-9. — View Citation

Lazzarino M, Arcaini L, Bernasconi P, Alessandrino EP, Gargantini L, Cairoli R, Orlandi E, Astori C, Brusamolino E, Pagnucco G, Colombo AA, Calatroni S, Iacona I, Regazzi MB, Morra E. A sequence of immuno-chemotherapy with Rituximab, mobilization of in vivo purged stem cells, high-dose chemotherapy and autotransplant is an effective and non-toxic treatment for advanced follicular and mantle cell lymphoma. Br J Haematol. 2002 Jan;116(1):229-35. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	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.	every 3 months for the first year after autotransplant and every 6 months after the first year of follow up	No

External Links

•   Web site of Division of Hematology, IRCCS Policlinico S. Matteo, University of Pavia, Italy