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Trial record 11 of 495 for:    LENALIDOMIDE AND every 28 days

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

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ClinicalTrials.gov Identifier: NCT00890552
Recruitment Status : Completed
First Posted : April 30, 2009
Results First Posted : March 22, 2017
Last Update Posted : March 22, 2017
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Stanley L Schrier, Stanford University

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Leukemia
Amyloidosis
Interventions Drug: Lenalidomide
Drug: Melphalan
Drug: Dexamethasone
Enrollment 25
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Lenalidomide, Melphalan and Dexamethasone (MDR)
Hide Arm/Group Description

The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.

Lenalidomide: Orally-administered lenalidomide 10 mg will be taken daily on days 1 to 21 of 28-day cycle. Lenalidomide is a a derivative of thalidomide.

Melphalan: Orally-administered melphalan 0.18 mg/kg will be taken on days 1 to 4 of a 28-day cycle. Melphalan is a phenylalanine derivative of mechlorethamine.

Dexamethasone: Orally-administered dexamethasone 40 mg will be taken on days 1; 8; 15; and 22 of a 28-day cycle. Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication.

Period Title: Enrollment and Pre-treatment
Started 25
Completed 24
Not Completed 1
Reason Not Completed
Death/ lost to follow up             1
Period Title: On-treatment
Started 24
Completed 14
Not Completed 10
Reason Not Completed
Early prog disease/ death             10
Arm/Group Title Lenalidomide, Melphalan and Dexamethasone (MDR)
Hide Arm/Group Description The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.
Overall Number of Baseline Participants 25
Hide Baseline Analysis Population Description
Lenalidomide-naïve adults with biopsy-proven amyloidosis manifested as measurable disease, ECOG ≤ 3
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 25 participants
67
(52 to 84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Female
9
  36.0%
Male
16
  64.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Hispanic or Latino
2
   8.0%
Not Hispanic or Latino
21
  84.0%
Unknown or Not Reported
2
   8.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   4.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
23
  92.0%
More than one race
0
   0.0%
Unknown or Not Reported
1
   4.0%
ECOG Performance Status (PS)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants
ECOG PS 1 12
ECOG PS 2 9
ECOG PS 3 4
[1]
Measure Description:

ECOG Performance Status. PS 0 = Fully active, able to carry on all pre-disease performance without restriction.

PS 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.

PS 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. PS 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours..

Hematologic disease burden  
Measure Type: Number
Unit of measure:  Percentage of participants
Number Analyzed 25 participants
Kappa free light chain (%) 20
Lambda free light chain (%) 80
1.Primary Outcome
Title Hematologic Response Rate
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects completing at least one full cycle of study treatment
Arm/Group Title Lenalidomide, Melphalan and Dexamethasone (MDR)
Hide Arm/Group Description:

The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.

Lenalidomide: Orally-administered lenalidomide 10 mg will be taken daily on days 1 to 21 of 28-day cycle. Lenalidomide is a a derivative of thalidomide.

Melphalan: Orally-administered melphalan 0.18 mg/kg will be taken on days 1 to 4 of a 28-day cycle. Melphalan is a phenylalanine derivative of mechlorethamine.

Dexamethasone: Orally-administered dexamethasone 40 mg will be taken on days 1; 8; 15; and 22 of a 28-day cycle. Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication.

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: participants
Complete Response (CR) 2
Very good Partial Response (VGPR) 4
Partial Response (PR) 8
No Response (NR) 9
Response not evaluable 1
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description Participants alive 12 months after starting MDR treatment.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects receiving MDR treatment.
Arm/Group Title Lenalidomide, Melphalan and Dexamethasone (MDR)
Hide Arm/Group Description:

The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.

Lenalidomide: Orally-administered lenalidomide 10 mg will be taken daily on days 1 to 21 of 28-day cycle. Lenalidomide is a a derivative of thalidomide.

Melphalan: Orally-administered melphalan 0.18 mg/kg will be taken on days 1 to 4 of a 28-day cycle. Melphalan is a phenylalanine derivative of mechlorethamine.

Dexamethasone: Orally-administered dexamethasone 40 mg will be taken on days 1; 8; 15; and 22 of a 28-day cycle. Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication.

Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: percentage of participants
58
3.Secondary Outcome
Title Event-free Survival (EFS)
Hide Description Assessed as the median value for EFS 12 months after starting MDR treatment
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants starting MDR treatment
Arm/Group Title Lenalidomide, Melphalan and Dexamethasone (MDR)
Hide Arm/Group Description:

The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.

Lenalidomide: Orally-administered lenalidomide 10 mg will be taken daily on days 1 to 21 of 28-day cycle. Lenalidomide is a a derivative of thalidomide.

Melphalan: Orally-administered melphalan 0.18 mg/kg will be taken on days 1 to 4 of a 28-day cycle. Melphalan is a phenylalanine derivative of mechlorethamine.

Dexamethasone: Orally-administered dexamethasone 40 mg will be taken on days 1; 8; 15; and 22 of a 28-day cycle. Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication.

Overall Number of Participants Analyzed 14
Median (Full Range)
Unit of Measure: months
3.15
(0.25 to 12)
4.Secondary Outcome
Title Duration of Response
Hide Description Assessed as the median value for the time from first partial response until progression; death; or last follow-up.
Time Frame 32 months
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who achieved at least a partial response (9 subjects were not included due to not having any response)
Arm/Group Title Lenalidomide, Melphalan and Dexamethasone (MDR)
Hide Arm/Group Description:

The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.

Lenalidomide: Orally-administered lenalidomide 10 mg will be taken daily on days 1 to 21 of 28-day cycle. Lenalidomide is a a derivative of thalidomide.

Melphalan: Orally-administered melphalan 0.18 mg/kg will be taken on days 1 to 4 of a 28-day cycle. Melphalan is a phenylalanine derivative of mechlorethamine.

Dexamethasone: Orally-administered dexamethasone 40 mg will be taken on days 1; 8; 15; and 22 of a 28-day cycle. Dexamethasone is an anti-inflammatory and immunosuppressant steroid medication.

Overall Number of Participants Analyzed 14
Median (Full Range)
Unit of Measure: months
9.1
(0 to 31.25)
Time Frame 12 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Lenalidomide, Melphalan and Dexamethasone (MDR)
Hide Arm/Group Description The 3-drug combination of orally-administered lenalidomide; melphalan; and dexamethasone (MDR) will be administered as nine 28-day cycles, with the option of continuing treatment with lenalidomide as single-agent.
All-Cause Mortality
Lenalidomide, Melphalan and Dexamethasone (MDR)
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Lenalidomide, Melphalan and Dexamethasone (MDR)
Affected / at Risk (%)
Total   19/25 (76.00%) 
Blood and lymphatic system disorders   
Anemia in Neoplastic disease *  1/25 (4.00%) 
Edema *  1/25 (4.00%) 
Neutrophils/granulocytes *  1/25 (4.00%) 
Hypoglycemia *  1/25 (4.00%) 
Hypovolemia *  1/25 (4.00%) 
Cardiac disorders   
Atrial fibrillation *  4/25 (16.00%) 
Ventricular tachycardia *  1/25 (4.00%) 
Atrial flutter *  1/25 (4.00%) 
Bradycardia *  1/25 (4.00%) 
Gastrointestinal disorders   
Hemorrhage *  2/25 (8.00%) 
Dehydration *  2/25 (8.00%) 
Constipation *  1/25 (4.00%) 
General disorders   
Death *  7/25 (28.00%) 
Syncope *  4/25 (16.00%) 
Infections and infestations   
Febrile neutropenia *  1/25 (4.00%) 
Pneumonia *  1/25 (4.00%) 
Metabolism and nutrition disorders   
Hyponatremia *  3/25 (12.00%) 
Primary Amyloidosis *  1/25 (4.00%) 
Renal failure *  1/25 (4.00%) 
Psychiatric disorders   
Altered mental status *  1/25 (4.00%) 
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Lenalidomide, Melphalan and Dexamethasone (MDR)
Affected / at Risk (%)
Total   23/25 (92.00%) 
Blood and lymphatic system disorders   
Bone and Blood Marrow *  5/25 (20.00%) 
Hypocalcemia *  3/25 (12.00%) 
Hemolysis *  6/25 (24.00%) 
INR *  2/25 (8.00%) 
Leukocytes *  2/25 (8.00%) 
Neutrophils/granulocytes *  4/25 (16.00%) 
Platelets *  18/25 (72.00%) 
Coagulation *  1/25 (4.00%) 
Edema: head and neck *  1/25 (4.00%) 
Edema: trunk/genital *  1/25 (4.00%) 
Lymphatics *  1/25 (4.00%) 
Cardiac disorders   
Hypotension *  3/25 (12.00%) 
Thrombotic microangiopathy *  2/25 (8.00%) 
Sinus arrhythmia *  2/25 (8.00%) 
Sinus bradycardia *  1/25 (4.00%) 
Ear and labyrinth disorders   
Auditory/Ear *  1/25 (4.00%) 
Hearing loss *  1/25 (4.00%) 
Eye disorders   
Vision-blurred *  2/25 (8.00%) 
Dry eye syndrome *  1/25 (4.00%) 
Ocular/Visual *  1/25 (4.00%) 
Gastrointestinal disorders   
Anorexia *  4/25 (16.00%) 
Constipation *  6/25 (24.00%) 
Diarrhea *  5/25 (20.00%) 
Distension/bloating *  3/25 (12.00%) 
Dry mouth *  3/25 (12.00%) 
Gastrointestinal *  8/25 (32.00%) 
Nausea *  3/25 (12.00%) 
Vomitting *  2/25 (8.00%) 
weight loss *  5/25 (20.00%) 
Ascites (non-malignant) *  1/25 (4.00%) 
Dysphagia *  1/25 (4.00%) 
General disorders   
Fatigue *  16/25 (64.00%) 
Fever *  5/25 (20.00%) 
Insomnia *  4/25 (16.00%) 
Mood alteration- Anxiety *  3/25 (12.00%) 
Pain *  12/25 (48.00%) 
Dehydration *  1/25 (4.00%) 
Rigors/chills *  1/25 (4.00%) 
dysarthria *  1/25 (4.00%) 
Hepatobiliary disorders   
Hematoma *  2/25 (8.00%) 
Hemoglobin *  2/25 (8.00%) 
Infections and infestations   
Edema: limbs *  11/25 (44.00%) 
Infection *  11/25 (44.00%) 
abscess *  1/25 (4.00%) 
Metabolism and nutrition disorders   
Hypoalbuminemia *  2/25 (8.00%) 
Creatinine *  3/25 (12.00%) 
Hyperglycemia *  3/25 (12.00%) 
Hypokalemia *  4/25 (16.00%) 
Hyponatremia *  5/25 (20.00%) 
Alkaline phosphatase *  1/25 (4.00%) 
AST, SGOT *  1/25 (4.00%) 
Hyperbilirubinemia *  1/25 (4.00%) 
Musculoskeletal and connective tissue disorders   
Muscle weakness *  2/25 (8.00%) 
Nervous system disorders   
Dizziness *  7/25 (28.00%) 
Neuropathy: sensory *  6/25 (24.00%) 
Neuropathy: motor *  1/25 (4.00%) 
Psychiatric disorders   
Depression *  1/25 (4.00%) 
Renal and urinary disorders   
Cystitis *  1/25 (4.00%) 
Dysuria *  1/25 (4.00%) 
Respiratory, thoracic and mediastinal disorders   
Cough *  2/25 (8.00%) 
Dysphagia *  10/25 (40.00%) 
Skin and subcutaneous tissue disorders   
Dermatology *  2/25 (8.00%) 
Rash/desquamation *  11/25 (44.00%) 
Dry skin *  1/25 (4.00%) 
Alopecia *  1/25 (4.00%) 
Petechiae/purpura *  1/25 (4.00%) 
Sweating *  1/25 (4.00%) 
Wound complication *  1/25 (4.00%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Brenda Hann, RN, MBA, CCRC
Organization: Stanford University School of Medicine
Phone: 650-723-0966
EMail: bhann@stanford.edu
Layout table for additonal information
Responsible Party: Stanley L Schrier, 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 )
First Submitted: April 28, 2009
First Posted: April 30, 2009
Results First Submitted: April 14, 2016
Results First Posted: March 22, 2017
Last Update Posted: March 22, 2017