Clinical Trial Result Information
Protocol number
M39044
Title of Study
Treatment of Mantle Cell Non Hodgkin’s Lymphoma with Rituximab after Autologous Marrow or Peripheral Blood Stem Cell Transplantation
Sponsor
Roche Products Pty Limited
Company division
Pharmaceutical
Product name
MabThera/Rituxan
Generic name
rituximab
Therapeutic area
Mantle Cell Lymphoma
Clinical study summary
This open label study assessed the efficacy and safety of MabThera (rituximab) in patients with mantle cell lymphoma who have received high dose chemotherapy followed by autologous bone marrow or peripheral blood stem cell transplantation. Patients received MabThera 375 mg/m² i.v. once a week for 4 weeks, 4-10 weeks post-transplant.
Study center(s)
6 centers in Australia.
Phase of development
IV
Objectives
Primary: To assess the tolerability of MabThera therapy in patients with mantle cell lymphoma who have received high dose chemotherapy followed by autologous peripheral blood progenitor cell or marrow transplantation.
Secondary: To evaluate the efficacy of MabThera therapy in patients with mantle cell lymphoma who have received high dose chemotherapy followed by autologous peripheral blood progenitor cell or marrow transplantation; to evaluate the effect of MabThera, where possible, on the level of residual mantle cell lymphoma, as detected by molecular (or flow cytometric) techniques, in the peripheral blood and bone marrow.
Methodology
The screening phase comprised patients with newly diagnosed or relapsed disease. Only those with chemosensitive disease and who underwent an autograft were eligible to enter the formal study and receive MabThera treatment. MabThera was administered weekly for 4 doses, 375 mg/m² i.v. Mononuclear cells were collected from marrow and/or lymph nodes, and DNA extracted, at screening and at intervals throughout the study.
Number of patients (planned/analyzed)
13 enrolled; 9 evaluable.
Diagnosis and main criteria for inclusion
Patients ≥ 18 and ≤ 65 years of age, with de novo or relapsed, stage III, IV or bulky (>8cm) stage II, mantle cell lymphoma, responding to induction or salvage chemotherapy, Karnofsky index >70 and haematological recovery by days 28-50 post-transplant.
Test product, dose and mode of administration or test procedure
MabThera (rituximab) 375 mg/m² i.v.
Duration of treatment
4 doses at weekly intervals
Reference therapy, dose and mode of administration or reference procedure
N/A
Criteria for evaluation (efficacy, safety)
Efficacy: Progression-free survival after MabThera, efficacy of B-cell depletion, immunologic recovery, median survival at follow-up, molecular status by PCR assay.
Safety: AEs; laboratory tests, Karnofsky index, number of infections.
Statistical methods
Overall survival was calculated from the time of transplant until death of any cause. Event-free survival was measured from transplant until relapse or death.
Summary (efficacy, safety, other results)
Of the 5 previously untreated patients, 3 remained in complete remission with follow-up of 33, 44 and 50 months from transplant to latest staging (CT scans and marrow biopsy within the preceding 6 months). One patient relapsed at 34 months, but remained alive at the end of the study. The remaining previously untreated patient died of bacterial sepsis and possible viral pneumonia 10 months post-transplant, having had complete response status 2 months earlier. Two of the 4 patients transplanted with chemosensitive relapse died of rapid onset respiratory failure 2-3 months after the last dose of MabThera. No infectious pathogens were isolated. The third patient in this group developed biopsy-proven progressive mantle cell lymphoma at day 104, and died of disease 30 months post-transplant. The remaining patient was alive, in complete remission, when last restaged 31 months post-transplant.
A total of 6 patients achieved PCR negativity, in two cases observed following MabThera therapy. Two of the 6 died without disease, while the remaining 4 remain alive in ongoing remission.
Conclusions
In this pilot study, 3/5 patients autografted after induction therapy and 1/4 patients autografted after relapse remained alive and in complete remission over 30 months post-transplant. Two patients relapsed, and 3 died of late onset respiratory failure, probably reflecting infection and/or aggressive conditioning in an older patient population. These preliminary results suggest that the combination of autografting and MabThera may lead to durable remissions in patients with chemosensitive mantle cell lymphoma.
Publications (references, if available)
Grigg, A. P., Bashford, J., Seymour, J. F. et al. Autografting followed by rituximab for chemosensitive mantle cell lymphoma: A pilot study and literature review. Leukemia & Lymphoma, June 2005; 46(6): 851-860
Date of report
12/1/2004
Click here for the protocol registry listing of this trial.
|
