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

Primary Purpose

Leukemia, Amyloidosis

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Lenalidomide
Melphalan
Dexamethasone
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Stanford University Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lenalidomide+Melphalan+Dexamethasone

Arm Description

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).

Outcomes

Primary Outcome Measures

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%).

Secondary Outcome Measures

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

Full Information

First Posted
April 28, 2009
Last Updated
February 1, 2017
Sponsor
Stanford University
Collaborators
Celgene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00890552
Brief Title
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

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
April 2009 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
Collaborators
Celgene Corporation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Amyloidosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lenalidomide+Melphalan+Dexamethasone
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid, L04AX04
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
Alkeran, Evomela, Sarcolysin, L-phenylalanine mustard (L-PAM), 4-[Bis(2-chloroethyl)amino]-L-phenylalanine
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Intensol, Decadron, Baycadron, Dexpak® Taperpak, Maxidex (dexamethasone ophthalmic suspension), Ozurdex (dexamethasone intravitreal implant)
Intervention Description
Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication. Orally-administered dexamethasone 40 mg orally once weekly of a 28-day cycle
Primary Outcome Measure Information:
Title
Hematologic Response Rate
Description
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%).
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Participants alive 12 months after starting MDR treatment.
Time Frame
12 months
Title
Event-free Survival (EFS)
Description
Assessed as the median value for EFS 12 months after starting MDR treatment
Time Frame
12 months
Title
Duration of Response
Description
Assessed as the median value for the time from first partial response until progression; death; or last follow-up.
Time Frame
32 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stanley L Schrier, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University Cancer Institute
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23091105
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.
Results Reference
background
PubMed Identifier
23716538
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.
Results Reference
result

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

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