Clinical trial NCT00883623: A Trial of Treatment With Lenalidomide-Melphalan-Dexamethasone in Patients With Primary (AL) Amyloidosis
Official title: A Prospective Single Center Trial of Treatment With Lenalidomide-Melphalan-Dexamethasone in Patients With AL Amyloidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Amyloidosis
Keywords: AL-Amyloidosis
Lenalidomide
Lead sponsor: Heidelberg University
Sponsor class: OTHER
Collaborators: name: Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH
First posted: 2009-04-17
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Complete response (CR) rate
timeFrame: 6 months: after 6 cycles of L-Mel-Dex
Secondary outcomes:
measure: Rate of hematological response (CR and PR)
timeFrame: 6 months
measure: Organ response rate
timeFrame: 3 months after discontinuation of L-Mel_Dex (maximum: 9 months)
measure: Correlation of cytogenetic aberrations and gene expression profiling (GEP) results with best hematological response to treatment
timeFrame: 6 months
measure: Retrospective comparison with a historical control group treated with Mel-Dex in our institution
timeFrame: 01.04.2012
measure: Toxicity (hematological and non-hematological)
timeFrame: 6 months
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University Clinic Heidelberg
Study officials:
affiliation: University Clinic Heidelberg - Department of Internal Medicine V
name: Stefan Schoenland, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.