Clinical trial NCT00890552: A Pilot Study of Lenalidomide, Melphalan and Dexamethasone in AL Amyloidosis
Official title: A Pilot Study of Lenalidomide, Melphalan and Dexamethasone in AL Amyloidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Leukemia
Amyloidosis
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2009-04-30
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This open-label trial will evaluate the use of lenalidomide; melphalan; and dexamethasone (MDR) to treat newly diagnosed or relapsed AL amyloidosis, over the course of nine 28-day cycles.

Detailed description: The study will evaluate the 3-drug combination of lenalidomide; melphalan; and dexamethasone (MDR) as the absence of disease progression or toxicity, patients will complete nine 28-day cycles of MDR therapy, with the option of continuing treatment with lenalidomide as single-agent. Patients received up to nine cycles of treatment, with the option to continue on lenalidomide as a single agent if they responded to treatment.

Eligibility criteria: INCLUSION CRITERIA

* Newly diagnosed or relapsed AL amyloidosis
* Biopsy-proven amyloidosis with evidence of an underlying plasma cell dyscrasia

  * abnormal clonal dominance of plasma cells in the bone marrow
  * detection of a monoclonal gammopathy by immunofixation electrophoresis of serum and/or urine
  * an abnormal serum free light chain or ratio, or AL fibrils seen on biopsy)
* Measurable disease defined by an abnormal serum-free light chain or monoclonal protein by immunofixation

  * proteinuria ≥ 0.5 g/day, cardiac involvement with interventricular septal thickness ≥ 15 mm
  * hepatomegaly in the absence of congestive heart failure with elevated alkaline phosphatase
* Age ≥ 18 years at the time of signing the informed consent form.
* All previous cancer therapy must have been discontinued at least 4 weeks prior to treatment in this study
* ECOG performance status of ≤ 3 at study entry
* Laboratory test results:

  * Absolute neutrophil count ≥ 1.0 x 10e9 / L
  * Platelet count ≥ 75 x 10e9 / L
  * Creatinine clearance ≥ 15 mL/ minute
  * Total bilirubin ≤ 2-fold upper limits of normal
* Disease-free of prior malignancies (excluding multiple myeloma) for ≥ 3 years with exception of:

  * currently treated basal cell
  * squamous cell carcinoma of the skin
  * carcinoma "in situ" of the cervix or breast.
* Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test
* Females of childbearing potential must either:

  * commit to continued abstinence from heterosexual intercourse
  * acceptable methods of birth control and agree to ongoing pregnancy testing
* Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy
* All study participants must be registered into the mandatory RevAssist program, and able to comply with its requirements
* Able to take aspirin (81 mg) daily • Understand and voluntarily sign an informed consent form
* Able to adhere to the study visit schedule and other protocol requirements

EXCLUSION CRITERIA

* Any serious medical condition that would prevent the subject from signing the informed consent form
* Pregnant
* breast-feeding females
* Use of any other experimental drug or therapy within 28 days of baseline
* Known hypersensitivity to thalidomide
* 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 positivity for human immunodeficiency virus HIV)

Primary outcomes:
measure: Hematologic Response Rate
timeFrame: 8 weeks
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 12 months
measure: Event-free Survival (EFS)
timeFrame: 12 months
measure: Duration of Response
timeFrame: 32 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Cancer Institute
state: California
Study officials:
affiliation: Stanford University
name: Stanley L Schrier, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, Schonland S, Hegenbart U, Comenzo R, Kastritis E, Dimopoulos MA, Jaccard A, Klersy C, Merlini G. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012 Dec 20;30(36):4541-9. doi: 10.1200/JCO.2011.37.7614. Epub 2012 Oct 22.
citation: Dinner S, Witteles W, Afghahi A, Witteles R, Arai S, Lafayette R, Schrier SL, Liedtke M. Lenalidomide, melphalan and dexamethasone in a population of patients with immunoglobulin light chain amyloidosis with high rates of advanced cardiac involvement. Haematologica. 2013 Oct;98(10):1593-9. doi: 10.3324/haematol.2013.084574. Epub 2013 May 28.