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

NCT00883623 | Completed Phase 2 DMC

• 2 other identifiers: 2008-001405-41GMIHO 005/2007 (191063)
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Primary Amyloidosis

Keywords

AL-Amyloidosis; Lenalidomide

Outcome Measures

Primary Outcomes (1)

• Complete response (CR) rate

  6 months: after 6 cycles of L-Mel-Dex

Secondary Outcomes (5)

• Rate of hematological response (CR and PR)

  6 months

• Organ response rate

  3 months after discontinuation of L-Mel_Dex (maximum: 9 months)

• Correlation of cytogenetic aberrations and gene expression profiling (GEP) results with best hematological response to treatment

  6 months

• Retrospective comparison with a historical control group treated with Mel-Dex in our institution

  01.04.2012

• Toxicity (hematological and non-hematological)

  6 months

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Treatment Arm

Drug: Lenalidomide

Interventions

Lenalidomide DRUG

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

Also known as: Revlimid

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Multiple Myeloma stage II and III (Durie and Salmon)
• Previous organ transplantation
• Not able to visit the Amyloid Clinic in Heidelberg once per month
• 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

Sponsors & Collaborators

• Heidelberg University: lead
• Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH: collaborator

Study Sites (1)

University Clinic Heidelberg

Heidelberg, 69120, Germany

Location

Related Publications (1)

• Hegenbart U, Bochtler T, Benner A, Becker N, Kimmich C, Kristen AV, Beimler J, Hund E, Zorn M, Freiberger A, Gawlik M, Goldschmidt H, Hose D, Jauch A, Ho AD, Schonland SO. Lenalidomide/melphalan/dexamethasone in newly diagnosed patients with immunoglobulin light chain amyloidosis: results of a prospective phase 2 study with long-term follow up. Haematologica. 2017 Aug;102(8):1424-1431. doi: 10.3324/haematol.2016.163246. Epub 2017 May 18.

  PMID: 28522573 DERIVED

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Stefan Schoenland, MD

  University Clinic Heidelberg - Department of Internal Medicine V

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 15, 2009
• First Posted: April 17, 2009
• Study Start: April 1, 2009
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: November 25, 2013

Record last verified: 2013-11

Locations

DE (1)