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| ID | Type | Description | Link |
|---|---|---|---|
| LNH 1-02 | Other Identifier | IRCCS Policlinico San Matteo |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| In vivo purging autotransplant | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Immunochemotherapy, in vivo purging and autrotransplant | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mario Lazzarino, M.D. | Division of Hematology, IRCCS Policlinico S. Matteo, University of Pavia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Division of Hematology, IRCCS Policlinico S. Matteo, University of Pavia | Pavia | 27100 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11841421 | Background | 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. | |
| 15170171 |
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Between January 2002 and September 2007, 64 patients with relapsed or refractory follicular lymphoma were enrolled in the trial
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| ID | Title | Description |
|---|---|---|
| FG000 | Immunochemotherapy, in Vivo Purging and Autotransplant | 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 · 109/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 s.c.) 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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|
| Background |
| 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. |
| 18344536 | Result | 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. |
| 25502635 | Derived | 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. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Immunochemotherapy, in Vivo Purging and Autotransplant | 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 · 109/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 s.c.) 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Number | 95% Confidence Interval | percent chance of PFS at 5 years | every 3 months for the first year after autotransplant and every 6 months after the first year of follow up |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Immunochemotherapy, in Vivo Purging and Autotransplant | 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 · 109/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 s.c.) 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. | 2 | 64 | 54 | 64 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| sepsis | General disorders | Systematic Assessment | One patient developed Escherichia coli sepsis during cytopenia, did not harvest PBSC and required intensive support and i.v. antimicrobial therapy |
| |
| Vasculitis | Vascular disorders | Systematic Assessment | One patient developed vasculitis during the cytopenic phase after autotransplant that resolved completely with steroids. |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hematological toxicity grade 3-4 | Blood and lymphatic system disorders | Systematic Assessment | 44 patients out of 61 developed grade 3-4 hematological toxicity after high dose Ara-C while 10 aut of 59 developed grade 3-4 hematological toxicity during autotransplant |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Luca Arcaini MD | Division of Hematology, Fondazione IRCCS Policlinico San Matteo, University of Pavia | +390382501308 | luca.arcaini@unipv.it |
| ID | Term |
|---|---|
| D008224 | Lymphoma, Follicular |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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