A Trial of Treatment With Lenalidomide-Melphalan-Dexamethasone in Patients With Primary (AL) Amyloidosis

Primary Amyloidosis Clinical Trial

— LEOMEX  

Official title:

A Prospective Single Center Trial of Treatment With Lenalidomide-Melphalan-Dexamethasone in Patients With AL Amyloidosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00883623
• Other study ID #: 2008-001405-41
• Secondary ID: GMIHO 005/2007 (
• Status: Completed
• Phase: Phase 2
• First received: April 15, 2009
• Last updated: November 21, 2013
• Start date: April 2009
• Est. completion date: February 2013

Study information

• Verified date: November 2013
• Source: Heidelberg University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The treatment with oral melphalan and prednisone has been recommended as standard treatment of AL amyloidosis but the results are rather disappointing. Another therapeutic option is pulsed high-dose dexamethasone + melphalan (Mel-Dex) with more encouraging results regarding the achievement of a faster disease response and higher rates of haematological remission. In the last 5 - 10 years, promising treatment outcomes after therapy with high-dose melphalan and autologous stem cell support have been reported by several groups but only highly selected patients are eligible for this treatment. Lenalidomide has been shown to be effective in phase II and III trials in MM patients. Because of the relationship to MM, Lenalidomide is a promising therapeutic option also for patients with AL amyloidosis. The addition of Lenalidomide to Mel-Dex could improve rate of complete response (CR) and organ response in patients not eligible for or refused high-dose chemotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

• Biopsy proven systemic untreated AL amyloidosis requiring systemic chemotherapy

• Not eligible for or refused HDM

• Measurable plasma cell disease

• Life expectancy > 3 months

• WHO performance status < 3

• NYHA < stage IV

• Understand and voluntarily sign an informed consent form

• Laboratory test results within these ranges Absolute neutrophil count > 1.5 x 109/L Platelet count > 100 x 109/L Creatinine Clearance / MDRD > 40 ml/min Total bilirubin > 2,5 mg/dL

• Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study.

Exclusion Criteria:

• Multiple Myeloma stage II and III (Durie and Salmon)

• Previous organ transplantation

• Not able to visit the Amyloid Clinic in Heidelberg once per month

• Refusal of aspiration of 100 ml bone marrow at study inclusion

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

• Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).

• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

• Use of any other experimental drug or therapy within 28 days of baseline.

• Known hypersensitivity to thalidomide.

• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.

• Any prior use of lenalidomide.

• Concurrent use of other anti-cancer agents or treatments.

• Known positive for HIV or infectious hepatitis, B or C.

• Patients who are in a depending position of the Sponsor or the Principal Investigator

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyloidosis
• Primary Amyloidosis

Intervention

Drug:
• Lenalidomide
Up to 6 cycles of oral L-Mel-Dex, every 28 days Revlimid® 10 mg daily for 21 days, (add on therapy), Melphalan 0.15 mg/kg/day day 1-4, Dexamethasone 20 mg day 1-4

Locations

Country	Name	City	State
Germany	University Clinic Heidelberg	Heidelberg

Sponsors (2)

Lead Sponsor	Collaborator
Heidelberg University	Gesellschaft für Medizinische Innovation - Hämatologie und Onkologie mbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response (CR) rate		6 months: after 6 cycles of L-Mel-Dex	No
Secondary	Rate of hematological response (CR and PR)		6 months	No
Secondary	Organ response rate		3 months after discontinuation of L-Mel_Dex (maximum: 9 months)	No
Secondary	Correlation of cytogenetic aberrations and gene expression profiling (GEP) results with best hematological response to treatment		6 months	No
Secondary	Retrospective comparison with a historical control group treated with Mel-Dex in our institution		01.04.2012	No
Secondary	Toxicity (hematological and non-hematological)		6 months	Yes

External Links

•   University Clinic Heidelberg - Department of Internal Medicine V