Bortezomib, Melphalan, and Dexamethasone in Treating Patients With Primary Amyloidosis or Light Chain Deposition Disease

Phase 2

Completed

• Conditions: Primary Systemic Amyloidosis; Light Chain Deposition Disease
• Interventions: Drug: bortezomib; Drug: dexamethasone; Drug: melphalan; Genetic: microarray analysis; Other: flow cytometry; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment

• Registration Number: NCT00520767
• Lead Sponsor: Barbara Ann Karmanos Cancer Institute

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.

Study Timeline

• Study First Submitted: 2007-08-24
• Study First Submitted QC: 2007-08-24
• Study First Posted: 2007-08-27
• Study Start: 2007-09
• Primary Completion: 2010-10
• Results First Submitted: 2015-03-18
• Results First Submitted QC: 2015-03-18
• Results First Posted: 2015-03-30
• Study Completion: 2019-06-06
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-20
• Last Update Posted: 2023-12-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Melphalan, Dexamethasone, Bortezomib,	flow cytometry	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
Melphalan, Dexamethasone, Bortezomib,	laboratory biomarker analysis	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
Melphalan, Dexamethasone, Bortezomib,	dexamethasone	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
Melphalan, Dexamethasone, Bortezomib,	microarray analysis	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
Melphalan, Dexamethasone, Bortezomib,	quality-of-life assessment	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
Melphalan, Dexamethasone, Bortezomib,	bortezomib	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
Melphalan, Dexamethasone, Bortezomib,	melphalan	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

Primary Outcome Measures

Name	Time	Method
Complete Hematologic Response	Up to 12 months

Secondary Outcome Measures

Name	Time	Method
Organ Response Rate (OrR)	Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.
Overall Survival	time from day of registration until 72 months.	time from day of registration until day of death.
Overall Hematologic Response Rate (OHR)	Beginning of cycles 4, 8, 12, 16 and 20, at follow up and end of study.
Time to Treatment Failure (TTF)	start of treatment until 72 months	Time from start of treatment until date of documented disease progression, removal from protocol due to toxicity, or death from any cause.

Trial Locations

Locations (7)

Providence Cancer Institute at Providence Hospital - Southfield Campus; 🇺🇸 Southfield, Michigan, United States

Boston University Cancer Research Center; 🇺🇸 Boston, Massachusetts, United States

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Rocky Mountain Cancer Centers/Rocky Mountain Blood & Marrow Transplant Program; 🇺🇸 Denver, Colorado, United States

Duke Comprehensive Cancer Center; 🇺🇸 Durham, North Carolina, United States

UPMC Cancer Centers; 🇺🇸 Pittsburgh, Pennsylvania, United States

Josephine Ford Cancer Center at Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States