Conditions: Primary Systemic Amyloidosis Light Chain Deposition Disease
Keywords: primary systemic amyloidosis light chain deposition disease
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 35
Healthy volunteers: no

Brief summary:
RATIONALE: Giving bortezomib together with melphalan and dexamethasone may be an effective treatment for primary amyloidosis and light chain deposition disease.

PURPOSE: This phase II trial is studying how well giving bortezomib together with melphalan and dexamethasone works in treating patients with primary amyloidosis or light chain deposition disease.

Detailed description:
OBJECTIVES:

Primary

* Determine the complete hematologic response rate at 12 months.

Secondary

* Determine the overall hematologic response rate.
* Determine the organ response rate.
* Determine time to treatment failure.
* Determine the overall survival.

OUTLINE: This is a multicenter study.

Patients receive oral melphalan on days 1-4, bortezomib IV on days 1, 8, 15, and 22, and dexamethasone orally or IV on days 1, 2, 8, 9, 15, 16, 22, and 23. Treatment repeats every 4-6 weeks for up to 20 courses in the absence of disease progression or unacceptable toxicity.

Blood, urine, and bone marrow aspirates are collected at baseline and periodically after treatment to permit the correlation of clinical results with measured molecular events. A single baseline peripheral blood DNA sample is collected for future association studies linking disease onset, progression, and response to administered therapy with single nucleotide polymorphisms. Blood plasma and urine samples are evaluated for proteomic markers associated with disease progression and therapeutic response. Peripheral blood RNA samples are evaluated for transcriptional response to treatment of peripheral blood lymphocytes. Bone marrow aspirates are collected to extract plasma cells by flow cytometry for gene expression profiling.

Quality of life is assessed at the beginning of each course.

Arms:
arm 1: Bortezomib 1.3 mg/m2 days 1, 8, 15, 22; Dexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23; Melphalan 9 mg/m2/day days 1-4

Interventions: intervention 1: bortezomib intervention 2: dexamethasone intervention 3: melphalan intervention 4: microarray analysis intervention 5: flow cytometry intervention 6: laboratory biomarker analysis intervention 7: quality-of-life assessment
Intervention descriptions: intervention 1: Bortezomib 1.3 mg/m2 days 1, 8, 15, 22 intervention 2: Dexamethasone 40 mg/d days 1, 2, 8, 9, 15, 16, 22, 23 intervention 3: Melphalan 9 mg/m2/day days 1-4 intervention 4: ≤28 days prior to enrollment intervention 5: Day 1 of cycles 6, 12, 18 and at end of study. intervention 6: ≤28 days prior to enrollment intervention 7: Start of each cycle

Protocol document: