Clinical Trial: A Trial for Systemic Light-chain (AL) Amyloidosis
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Randomized Open-label Multicenter Phase III Trial of Melphalan and Dexamethasone (MDex) Versus Bortezomib, Melphalan and Dexamethasone (BMDex) for Untreated Patients With Systemic Light-chain (AL) A
Brief Summary:
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.
Detailed Summary:
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,
- cardiac stage I,
- cardiac stage II.
After strat
Sponsor: European Myeloma Network
Current Primary Outcome: Number of Patients in CR and PR measured by level of serum light chain monoclonal protein [ Time Frame: 3 cycles of therapy ]
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.
Original Primary Outcome: Same as current
Current Secondary Outcome: Compare haematology response [ Time Frame: 2 years ]
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.
Original Secondary Outcome: Same as current
Information By: European Myeloma Network
Dates:
Date Received: January 10, 2011
Date Started: January 2011
Date Completion:
Last Updated: March 9, 2017
Last Verified: August 2016
