Immunochemotherapy, in Vivo Purging, PBSC Mobilization and Autotransplant in Relapsed or Refractory Follicular Lymphoma
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| ClinicalTrials.gov Identifier: NCT00366275 |
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Recruitment Status :
Completed
First Posted : August 21, 2006
Results First Posted : October 18, 2010
Last Update Posted : October 31, 2012
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Follicular Lymphoma | Procedure: Immunochemotherapy, in vivo purging and autrotransplant | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 64 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase II of Immunochemotherapy, in Vivo Purging, PBSC Mobilization and Autotransplant in Patients With Relapsed or Refractory Follicular Lymphoma |
| Study Start Date : | January 2002 |
| Actual Primary Completion Date : | January 2007 |
| Actual Study Completion Date : | September 2007 |
| Arm | Intervention/treatment |
|---|---|
| Experimental: In vivo purging autotransplant |
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. |
- Progression-free Survival [ Time Frame: 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.
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| Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00366275
| Italy | |
| Division of Hematology, IRCCS Policlinico S. Matteo, University of Pavia | |
| Pavia, Italy, 27100 | |
| Principal Investigator: | Mario Lazzarino, M.D. | Division of Hematology, IRCCS Policlinico S. Matteo, University of Pavia |
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Luca Arcaini, MD, IRCCS Policlinico S. Matteo |
| ClinicalTrials.gov Identifier: | NCT00366275 |
| Other Study ID Numbers: |
ML17165 LNH 1-02 ( Other Identifier: IRCCS Policlinico San Matteo ) |
| First Posted: | August 21, 2006 Key Record Dates |
| Results First Posted: | October 18, 2010 |
| Last Update Posted: | October 31, 2012 |
| Last Verified: | October 2012 |
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follicular lymphoma rituximab immunochemotherapy peripheral blood stem cells (PBSC) mobilization |
in vivo purging autotransplant bcl-2 rearrangement molecular response |
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Lymphoma Lymphoma, Follicular Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders |
Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin |