A Pilot Study of Lenalidomide, Melphalan and Dexamethasone in AL Amyloidosis

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Pilot Study of Lenalidomide, Melphalan and Dexamethasone in AL Amyloidosis

Conditions
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Leukemia, Amyloidosis

Intervention / Treatment
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* Drug: Lenalidomide
* Drug: Melphalan
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenalidomide+Melphalan+Dexamethasone<br>Patients received lenalidomide 10 mg/day orally on days 1-21, melphalan 0.18 mg/kg orally on days 1-4, and dexamethasone 40 mg orally once weekly of a 28-day cycle (MDR treatment). | Drug: Lenalidomide<br>* Lenalidomide is a a derivative of thalidomide. Orally-administered lenalidomide 10 mg will be taken daily on days 1 to 21 of 28-day cycle.<br>* Other names: L04AX04;Drug: Melphalan<br>* Melphalan is a phenylalanine derivative of mechlorethamine. Orally-administered melphalan 0.18 mg/kg will be taken on days 1 to 4 of a 28-day cycle<br>* Other names: 4-[Bis(2-chloroethyl)amino]-L-phenylalanine;Drug: Dexamethasone<br>* Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication. Orally-administered dexamethasone 40 mg orally once weekly of a 28-day cycle<br>* Other names: Ozurdex (dexamethasone intravitreal implant);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematologic Response Rate | At the end of each treatment cycle (4 weeks), hematologic response rate as assessed. Hematologic response was considered to be amyloid complete response (normal FLC ratio and negative serum and urine immunofixation); very good partial response (difference between involved and uninvolved FLCs [dFLC] < 40 mg/L); or partial response (dFLC decrease > 50%). | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Participants alive 12 months after starting MDR treatment. | 12 months | 
| Event-free Survival (EFS) | Assessed as the median value for EFS 12 months after starting MDR treatment | 12 months | 
| Duration of Response | Assessed as the median value for the time from first partial response until progression; death; or last follow-up. | 32 months |