64 research outputs found
an interim analysis from the prospective GMMG-MM5 trial
We investigated the impact of subcutaneous versus intravenous bortezomib in
the MM5 trial of the German-Speaking Myeloma Multicenter Group which compared
bortezomib, doxorubicin, and dexamethasone with bortezomib, cyclophosphamide,
and dexamethasone induction therapy in newly diagnosed multiple myeloma. Based
on data from relapsed myeloma, the route of administration for bortezomib was
changed from intravenous to subcutaneous after 314 of 604 patients had been
enrolled. We analyzed 598 patients who received at least one dose of trial
medication. Adverse events were reported more frequently in patients treated
with intravenous bortezomib (intravenous=65%; subcutaneous=56%, P=0.02). Rates
of grade 2 or more peripheral neuropathy were higher in patients treated with
intravenous bortezomib during the third cycle (intravenous=8%;
subcutaneous=2%, P=0.001). Overall response rates were similar in patients
treated intravenously or subcutaneously. The presence of International Staging
System stage III disease, renal impairment or adverse cytogenetic
abnormalities did not have a negative impact on overall response rates in
either group. To our knowledge this is the largest study to present data
comparing subcutaneous with intravenous bortezomib in newly diagnosed myeloma.
We show better tolerance and similar overall response rates for subcutaneous
compared to intravenous bortezomib. The clinical trial is registered at
eudract.ema.europa.eu as n. 2010-019173-16
Daratumumab after allogeneic hematopoietic cell transplantation for multiple myeloma is safe and synergies with pre-existing chronic graft versus host disease. A retrospective study from the CMWP EBMT
a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma
Background Despite novel therapeutic agents, most multiple myeloma (MM)
patients eventually relapse. Two large phase III trials have shown
significantly improved response rates (RR) of lenalidomide/dexamethasone
compared with placebo/dexamethasone in relapsed MM (RMM) patients. These
results have led to the approval of lenalidomide for RMM patients and
lenalidomide/dexamethasone has since become a widely accepted second-line
treatment. Furthermore, in RMM patients consolidation with high-dose
chemotherapy plus autologous stem cell transplantation has been shown to
significantly increase progression free survival (PFS) as compared to
cyclophosphamide in a phase III trial. The randomized prospective ReLApsE
trial is designed to evaluate PFS after lenalidomide/dexamethasone induction,
high-dose chemotherapy consolidation plus autologous stem cell transplantation
and lenalidomide maintenance compared with the well-established
lenalidomide/dexamethasone regimen in RMM patients. Methods/Design ReLApsE is
a randomized, open, multicenter phase III trial in a planned study population
of 282 RMM patients. All patients receive three lenalidomide/dexamethasone
cycles and - in absence of available stem cells from earlier harvesting -
undergo peripheral blood stem cell mobilization and harvesting. Subsequently,
patients in arm A continue on consecutive lenalidomide/dexamethasone cycles,
patients in arm B undergo high dose chemotherapy plus autologous stem cell
transplantation followed by lenalidomide maintenance until discontinuation
criteria are met. Therapeutic response is evaluated after the 3rd (arm A + B)
and the 5th lenalidomide/dexamethasone cycle (arm A) or 2 months after
autologous stem cell transplantation (arm B) and every 3 months thereafter
(arm A + B). After finishing the study treatment, patients are followed up for
survival and subsequent myeloma therapies. The expected trial duration is 6.25
years from first patient in to last patient out. The primary endpoint is PFS,
secondary endpoints include overall survival (OS), RR, time to best response
and the influence of early versus late salvage high dose chemotherapy plus
autologous stem cell transplantation on OS. Discussion This phase III trial is
designed to evaluate whether high dose chemotherapy plus autologous stem cell
transplantation and lenalidomide maintenance after lenalidomide/dexamethasone
induction improves PFS compared with the well-established continued
lenalidomide/dexamethasone regimen in RMM patients. Trial registration:
ISRCTN16345835 (date of registration 2010-08-24)
Rationale and design of the German-speaking myeloma multicenter group (GMMG) trial HD6: a randomized phase III trial on the effect of elotuzumab in VRD induction/consolidation and lenalidomide maintenance in patients with newly diagnosed myeloma
Background: Despite major advances in therapy, multiple myeloma is still an incurable malignancy in the majority of patients. To increase survival, deeper remissions (i.e. CR) translating into longer PFS need to be achieved. Incorporation of new drugs (i.e. bortezomib and lenalidomide) as induction and maintenance treatment in an intensified treatment concept, including high dose melphalan (200 mg/m2), has resulted in increased CR rates, and is considered the standard of care for younger patients. Elotuzumab in combination with lenalidomide and dexamethasone has given better results as lenalidomide and dexamethasone alone in a phase III trial. The GMMG-HD6 trial will be the first phase III trial investigating the role of elotuzumab in combination with bortezomib, lenalidomide and dexamethasone (VRD) induction/consolidation and lenalidomide maintenance within a high dose concept.
Methods: GMMG-HD6 is a randomized, open, multicenter phase III trial. The planned recruitment number is 564 NDMM patients. All patients will receive 4 VRD cycles as induction and undergo peripheral blood stem cell mobilization and harvesting. Thereafter they will be treated with high dose melphalan therapy plus autologous stem cell transplantation followed by 2 cycles of VRD consolidation and lenalidomide maintenance. Patients in arm B1 + B2 will additionally receive elotuzumab in the induction phase, whereas patients in A2 + B2 will be treated with elotuzumab added to consolidation and maintenance. The primary endpoint of the trial is PFS. Secondary objectives and endpoints are OS, CR rates after induction therapy comparing the two arms VRD (A1 + A2) vs VRD + elotuzumab (B1 + B2), CR rates after consolidation treatment, best response to treatment during the study, time to progression (TTP), duration of response (DOR), toxicity and quality of life.
Results: Since this is the publication of a study protocol of an ongoing study, no results can be presented.
Discussion: This phase III trial is designed to evaluate whether the addition of elotuzumab to an intensified treatment concept with high dose melphalan chemotherapy plus autologous stem cell transplantation and induction, consolidation and maintenance treatment with bortezomib and lenalidomide is able to improve PFS compared to the same concept without elotuzumab.
Trial registration: NCT02495922 on June 24th, 2015
Rationale and design of the German-Speaking Myeloma Multicenter Group (GMMG) trial ReLApsE: a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma
Optimization of Rituximab for the Treatment of Diffuse Large B-Cell Lymphoma (II): Extended Rituximab Exposure Time in the SMARTE-R-CHOP-14 Trial of the German High-Grade Non-Hodgkin Lymphoma Study Group
Purpose To study pharmacokinetics, toxicity, and efficacy of prolonged rituximab exposure in elderly patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods In the SMARTE-R-CHOP-14 trial, rituximab 375 mg/m(2) was administered, together with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone on a 14-day schedule (6xR-CHOP-14), on days -4, 0, 10, 29, 57, 99, 155, and 239. Pharmacokinetics and outcome were to be compared with those of patients who had received 6xR-CHOP-14 in combination with eight 2-week applications of rituximab in the RICOVER-60 (Rituximab With CHOP Over Age 60 Years) trial. Results The complete response (CR)/unconfirmed CR rate was 85% in 189 evaluable patients, 90% for 90 good-prognosis patients (International Prognostic Index [IPI], 1 or 2), and 81% for 99 poor-prognosis patients (IPI, 3 to 5); 3-year event-free survival (EFS) was 71%, 75%, and 67%, respectively; and 3-year overall survival (OS) was 84%, 88%, and 80%, respectively, with no differences between men and women. The preplanned historical comparison with 306 RICOVER-60 patients (good prognosis, n = 183; poor prognosis, n = 123) revealed no outcome differences for all and good-prognosis patients; however, the longer exposure time in SMARTE-R-CHOP-14 compared with RICOVER-60 was associated with better 3-year EFS (67% v 54%) and OS (80% v 67%) in poor-prognosis patients. Conclusion Extended rituximab exposure compared with eight 2-week applications in combination with 6xR-CHOP-14 significantly improved outcome of elderly poor-prognosis patients without increasing toxicity. To our knowledge, results obtained with the SMARTE-R-CHOP-14 rituximab schedule are the best reported for elderly patients with DLBCL to date. In the subgroup of poor-prognosis patients treated with extended rituximab exposure, the outcome seemed superior to that of a similar historical cohort of patients treated with 6xR-CHOP-14 plus 2-week rituximab, with similar toxicity. A randomized comparison of the two schedules is warranted. (C) 2014 by American Society of Clinical Oncolog
Increased rituximab (R) doses and effect on risk of elderly male patients with aggressive CD20+ B-cell lymphomas: Results from the SEXIE-R-CHOP-14 trial of the DSHNHL.
Optimization of Rituximab for Treatment of DLBCL in Young, High-Risk Patients-Results of the Dense-R-CHOEP Trial of the German High-Grade Lymphoma Study Group
Profound Impact of Sample Processing Delay on Gene Expression of Multiple Myeloma Plasma Cells
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