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

NCT ID: NCT00366275

Last Updated: 2012-10-31

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-01-31

Study Completion Date

2007-09-30

Brief Summary

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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

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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.

Conditions

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Follicular Lymphoma

Keywords

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follicular lymphoma rituximab immunochemotherapy peripheral blood stem cells (PBSC) mobilization in vivo purging autotransplant bcl-2 rearrangement molecular response

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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In vivo purging autotransplant

Group Type EXPERIMENTAL

Immunochemotherapy, in vivo purging and autrotransplant

Intervention Type PROCEDURE

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.

Interventions

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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.

Intervention Type PROCEDURE

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role lead

Responsible Party

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Luca Arcaini

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Mario Lazzarino, M.D.

Role: PRINCIPAL_INVESTIGATOR

Division of Hematology, IRCCS Policlinico S. Matteo, University of Pavia

Locations

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Division of Hematology, IRCCS Policlinico S. Matteo, University of Pavia

Pavia, , Italy

Site Status

Countries

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Italy

References

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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.

Reference Type BACKGROUND
PMID: 11841421 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15170171 (View on PubMed)

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.

Reference Type RESULT
PMID: 18344536 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25502635 (View on PubMed)

Related Links

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http://www.ematologia-pavia.it/

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

Other Identifiers

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LNH 1-02

Identifier Type: OTHER

Identifier Source: secondary_id

ML17165

Identifier Type: -

Identifier Source: org_study_id