Risk-adapted Therapy for Primary Systemic (AL) Amyloidosis

March 24, 2015 updated by: FDA Office of Orphan Products Development

Risk-adapted Therapy for AL Amyloidosis

High-dose melphalan (MEL) with autologous stem cell transplant (SCT) is an effective therapy for systemic AL amyloidosis (AL), but treatment-related mortality (TRM) has historically been high. The investigators performed a phase II trial of risk-adapted SCT followed by adjuvant dexamethasone (dex) and thalidomide (thal) in an attempt to reduce TRM and improve response rates. Patients with newly diagnosed AL involving £2 organ systems were assigned to MEL 100, 140, or 200 mg/m2 with SCT, based on age, renal function and cardiac involvement. Patients with persistent clonal plasma cell disease 3 months post-SCT received 9 months of adjuvant thal/dex (or dex if there was a history of deep vein thrombosis or neuropathy). TRM was 4.4%. Thirty-one patients began adjuvant therapy, with 16 (52%) completing 9 months of treatment and 13 (42%) achieving an improvement in hematological response. By intention-to-treat, overall hematological response rate was 71% (36% complete response) with 44% having organ responses. With a median follow-up of 31 months, 2-year survival was 84% (95% confidence interval: 73%, 94%). Risk-adapted SCT with adjuvant thal/ dex is feasible and results in low TRM and high hematological and organ response rates in AL patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

High-dose melphalan (MEL) with autologous stem cell transplant (SCT) is an effective therapy for systemic AL amyloidosis (AL), but treatment-related mortality (TRM) has historically been high. The investigators performed a phase II trial of risk-adapted SCT followed by adjuvant dexamethasone (dex) and thalidomide (thal) in an attempt to reduce TRM and improve response rates. Patients (n=45) with newly diagnosed AL involving £2 organ systems were assigned to MEL 100, 140, or 200 mg/m2 with SCT, based on age, renal function and cardiac involvement. Patients with persistent clonal plasma cell disease 3 months post-SCT received 9 months of adjuvant thal/dex (or dex if there was a history of deep vein thrombosis or neuropathy). Organ involvement was kidney (67%), heart (24%), liver/GI (22%) and peripheral nervous system (18%), with 31% having two organs involved. TRM was 4.4%. Thirty-one patients began adjuvant therapy, with 16 (52%) completing 9 months of treatment and 13 (42%) achieving an improvement in hematological response. By intention-to-treat, overall hematological response rate was 71% (36% complete response) with 44% having organ responses. With a median follow-up of 31 months, 2-year survival was 84% (95% confidence interval: 73%, 94%). Risk-adapted SCT with adjuvant thal/ dex is feasible and results in low TRM and high hematological and organ response rates in AL patients.(British Journal of Haematology 2007;139:224-33)

Study Type

Interventional

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

FDA Office of Orphan Products Development

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2002

Study Completion (Actual)

September 1, 2005

Study Registration Dates

First Submitted

July 28, 2011

First Submitted That Met QC Criteria

February 2, 2012

First Posted (Estimate)

February 6, 2012

Study Record Updates

Last Update Posted (Estimate)

March 25, 2015

Last Update Submitted That Met QC Criteria

March 24, 2015

Last Verified

July 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2174

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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