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

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Stanley L Schrier, Stanford University
ClinicalTrials.gov Identifier:
NCT00890552
First received: April 28, 2009
Last updated: February 1, 2017
Last verified: February 2017
  Purpose
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.

Condition Intervention
Leukemia
Amyloidosis
Drug: Lenalidomide
Drug: Melphalan
Drug: Dexamethasone

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Pilot Study of Lenalidomide, Melphalan and Dexamethasone in AL Amyloidosis

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Hematologic Response Rate [ Time Frame: 8 weeks ]
    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) [ Time Frame: 12 months ]
    Participants alive 12 months after starting MDR treatment.

  • Event-free Survival (EFS) [ Time Frame: 12 months ]
    Assessed as the median value for EFS 12 months after starting MDR treatment

  • Duration of Response [ Time Frame: 32 months ]
    Assessed as the median value for the time from first partial response until progression; death; or last follow-up.


Enrollment: 25
Study Start Date: April 2009
Study Completion Date: October 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide+Melphalan+Dexamethasone
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

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.

Other Names:
  • Revlimid
  • L04AX04
Drug: Melphalan

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

Other Names:
  • Alkeran
  • Evomela
  • Sarcolysin
  • L-phenylalanine mustard (L-PAM)
  • 4-[Bis(2-chloroethyl)amino]-L-phenylalanine
Drug: Dexamethasone

Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication.

Orally-administered dexamethasone 40 mg orally once weekly of a 28-day cycle

Other Names:
  • Intensol
  • Decadron
  • Baycadron
  • Dexpak® Taperpak
  • Maxidex (dexamethasone ophthalmic suspension)
  • Ozurdex (dexamethasone intravitreal implant)

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00890552

Locations
United States, California
Stanford University Cancer Institute
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Celgene Corporation
Investigators
Principal Investigator: Stanley L Schrier, MD Stanford University
  More Information

Publications:
Responsible Party: Stanley L Schrier, Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00890552     History of Changes
Other Study ID Numbers: IRB-15213
RV-AMYL-PI-0375 ( Other Identifier: Celgene Reference number )
SU-09192008-1300 ( Other Identifier: Stanford University )
HEM0010 ( Other Identifier: OnCore )
Study First Received: April 28, 2009
Results First Received: April 14, 2016
Last Updated: February 1, 2017
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Thalidomide
Melphalan
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on March 24, 2017