A Phase 3 interventional study of BMDex in AL Amyloidosis, sponsored by European Myeloma Network B.V.. Completed at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-03-10.
Sponsored by European Myeloma Network B.V. · Phase 3, Interventional, and Treatment
In this multi-center phase III trial, untreated patients diagnosed with AL who are not candidates for stem cell transplant with melphalan 200 mg/m2 are the target population. Stage I and II patients will be eligible. Stage III patients will be enrolled in an ancillary phase II study. Eligible patients will be stratified as cardiac stage I or stage II and then randomized to receive MDex or BMDex.
Primary objective is to compare hematologic(clonal) response i.e. the rate of complete response (CR) + partial response (PR) defined according to the criteria of the International Society for Amyloidosis consensus.
Design In this multi-center phase III trial, untreated patients diagnosed with AL who are not candidates for stem cell transplant with melphalan 200 mg/m2 are the target population. Patients who are eligible for SCT with melphalan 200 mg/m2 but who decline to undergo transplantation will be enrolled in the study as a subgroup with stratified randomization. Because many newly diagnosed AL patients present with limited organ reserve, the eligibility criteria take into consideration the impact of cardiac involvement on overall survival using cardiac biomarker staging. Stage I and II patients will be eligible. Stage III patients will be enrolled in an ancillary phase II study. Eligible patients will be stratified as cardiac stage I or stage II and then randomized to receive MDex or BMDex.
Intervention Untreated patients with AL amyloidosis will be offered treatment on this study. After being screened and found eligible, patients will be stratified based on cardiac stage as stage I or stage II. Thresholds for cTnT, cTnI, and NT-proBNP are \<0.035 microg/L, \<0.1 microg/L, and \<332 ng/L respectively. For stage I patients both cTnT or cTnI and NT-proBNP are below the threshold. For stage II patients either troponin or NT-proBNP are above the threshold.
Patients eligible for SCT with melphalan 200 mg/m2 who decline transplant will be considered an additional stratum and randomized separately.
Thus, there will be the following strata:
0.patients eligible for SCT with melphalan 200 mg/m2 who decline transplant,
After stratification, patients will then be randomized to receive either A: MDex:oral melphalan at 0.22 mg/kg and dexamethasone at 40 mg daily for 4 consecutive days every 28 days (MDex) or B: BMDex:cycles 1 and 2 = MDex with bortezomib at 1.3 mg/m2 i.v. on days 1, 4, 8 and 11 of a 28 day cycle,cycles 3 - 8 = MDex with bortezomib at 1.3 mg/m2 i.v. on days 1, 8, 15 and 22 of a 35 day cycle.
Treatment will start within 2 weeks after randomization.
Treatment is continued until
On the first day of each new treatment cycle and before each bortezomib dose, the patient will be evaluated for possible toxicities that may have occurred after the previous dose(s). Toxicities are to be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0. Dose modifications or delays will be made based on the toxicity experienced during the previous cycle of therapy or newly encountered on Day 1 of a cycle. Dose reduction steps are presented.
The start of a new cycle can be delayed on a weekly basis (for a maximum of 3 weeks)until recovery from toxicity to a level allowing continuation of therapy. Delay of a new cycle for more than 3 weeks can only occur if a clear clinical benefit has been observed. Otherwise, if there is a delay in the start of a new cycle of more than 3 weeks due to insufficient recovery from toxicity, subjects will discontinue study drug and have procedures performed as outlined for the End of Treatment Visit in the Schedule of Events.
During treatment, prophylactic medications will include acyclovir 400 mg twice daily with dose adjusted for renal function, ciprofloxacin 250 mg twice a day on days 1-7 of each cycle, and a proton-pump inhibitor. Supportive measures will be used. Patients will be seen in clinic by their physicians prior to beginning each cycle of therapy.
167 studies on the registry are indexed under Immunoglobulin Light-chain Amyloidosis; 57 are open to participants now.
This study's enrollment of 110 is above the median of 37 across 120 interventional studies indexed under Immunoglobulin Light-chain Amyloidosis.
Browse Immunoglobulin Light-chain Amyloidosis studies →European Myeloma Network B.V. is the lead sponsor of 17 studies on the registry; 4 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
MDex: Administration of oral melphalan (M) at 0.22 mg/kg and dexamethasone (Dex) at 40 mg daily for 4 consecutive days every 28 days (MDex) until end of therapy
BMDex: cycles 1 and 2 = MDex with bortezomib (B) at 1.3 mg/m2 i.v. on days 1, 4, 8 and 11 of a 28 day cycle, cycles 3 - 8 = MDex with bortezomib at 1.3 mg/m2 i.v. on days 1, 8, 15 and 22 of a 35 day cycle.
Drug: BMDex
BMDex: cycles 1 and 2 = MDex with bortezomib (B) at 1.3 mg/m2 i.v. on days 1, 4, 8 and 11 of a 28 day cycle, cycles 3 - 8 = MDex with bortezomib at 1.3 mg/m2 i.v. on days 1, 8, 15 and 22 of a 35 day cycle.
Also known as: Bortezomid, Melphalan, Dexametasone
Number of Patients in CR and PR measured by level of serum light chain monoclonal protein
As defined by the International Society for Amyloidosis consensus. Complete response: * serum and urine IF negative, * normal FLC ratio, * bone marrow PC \<5% Partial response if: * serum monoclonal \>0.5 g/dL, a 50% reduction, * FLC in urine visible and \>100 mg/day and 50% reduction, * FLC \>2 times upper normal and 50% reduction. Progressive disease * from CR, abnormal FLC ratio * from PR or stable disease, 50% increase in monoclonal protein to \>0.5 g/dL, or 50% increase in urine to \>200 mg/day, or FLC increase of 50% to \>100 mg/L. Stable disease: no CR, no PR, no progression.
Time frame: 3 cycles of therapy
Compare haematology response
To compare in patients treated with MDex or BMDex: * complete hematologic response rate after 3 cycles and after completion of therapy; * hematologic response rate at completion of therapy; * organ response rates at 3, 6, 9 and 12 months; * treatment-related mortality; * toxicity; * overall and progression-free survival; * time to hematologic and organ response; * quality of life.
Time frame: 2 years
This study is completed, as verified in Aug 2016. You cannot join it, but the record below documents what was studied.
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European Myeloma Network B.V.