Clinical trial NCT00366275: Immunochemotherapy, in Vivo Purging, PBSC Mobilization and Autotransplant in Relapsed or Refractory Follicular Lymphoma
Official title: Phase II of Immunochemotherapy, in Vivo Purging, PBSC Mobilization and Autotransplant in Patients With Relapsed or Refractory Follicular Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Follicular Lymphoma
Keywords: follicular lymphoma
rituximab
immunochemotherapy
peripheral blood stem cells (PBSC) mobilization
in vivo purging
autotransplant
bcl-2 rearrangement
molecular response
Lead sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia
Sponsor class: OTHER
First posted: 2006-08-21
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Progression-free Survival
timeFrame: every 3 months for the first year after autotransplant and every 6 months after the first year of follow up
Secondary outcomes:
Other outcomes:
Locations:
city: Pavia
country: Italy
facility: Division of Hematology, IRCCS Policlinico S. Matteo, University of Pavia
Study officials:
affiliation: Division of Hematology, IRCCS Policlinico S. Matteo, University of Pavia
name: Mario Lazzarino, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1046/j.1365-2141.2002.03256.x.
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. doi: 10.1038/sj.bmt.1704551.
citation: 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. Immunochemotherapy with in vivo purging and autotransplant induces long clinical and molecular remission in advanced relapsed and refractory follicular lymphoma. Ann Oncol. 2008 Jul;19(7):1331-1335. doi: 10.1093/annonc/mdn044. Epub 2008 Mar 15.
citation: Arcaini L, Morello L, Tucci A, Rusconi C, Ladetto M, Rattotti S, Bonfichi M, Bottelli C, Gabutti C, Bernasconi P, Varettoni M, Gotti M, Troletti D, Guerrera ML, Fiaccadori V, Sciarra R, Ferretti VV, Alessandrino EP, Rossi G, Morra E. Autologous stem cell transplantation with in vivo purged progenitor cells shows long-term efficacy in relapsed/refractory follicular lymphoma. Am J Hematol. 2015 Mar;90(3):230-4. doi: 10.1002/ajh.23919.