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Lenalidomide, Cyclophosphamide, and Dexamethasone in Treating Patients With Primary Systemic Amyloidosis

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ClinicalTrials.gov Identifier: NCT00564889
Recruitment Status : Completed
First Posted : November 29, 2007
Results First Posted : August 12, 2011
Last Update Posted : May 14, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma and Plasma Cell Neoplasm
Interventions Drug: cyclophosphamide
Drug: dexamethasone
Drug: lenalidomide
Enrollment 35
Recruitment Details Thirty-five(35) participants were recruited between December 2007 and November 2008 at Mayo Clinic.
Pre-assignment Details  
Arm/Group Title Len/Cyc/Dex
Hide Arm/Group Description

Lenalidomide (Len) 15mg daily (days 1-21)

Cyclophosphamide (Cyc) 300 mg/m^2 (days 1, 8, 15)

Dexamethasone (Dex) 40 mg weekly

Period Title: Overall Study
Started 35
Completed 6
Not Completed 29
Reason Not Completed
Death             7
Adverse Event             12
Alternative treatment             3
Disease progression             3
Other, not specified             4
Arm/Group Title Len/Cyc/Dex
Hide Arm/Group Description Lenalidomide (Len) 15mg daily (days 1-21); Cyclophosphamide (Cyc) 300 mg/m^2 (days 1, 8, 15); Dexamethasone (Dex) 40 mg weekly
Overall Number of Baseline Participants 35
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 35 participants
64
(44 to 82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants
Female
16
  45.7%
Male
19
  54.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 35 participants
35
Received Previous Treatment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants
Yes 11
No 24
Had a Prior Stem Cell Transplant  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 35 participants
Yes 7
No 28
1.Primary Outcome
Title Number of Participants Who Achieved a Confirmed Response Defined as a Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR)
Hide Description

Response that was confirmed on 2 consecutive evaluations during treatment.

Complete Response(CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and <5% plasma cells in bone marrow.

Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <=100 mg per 24 hours.

Partial Response(PR): >=50% reduction in serum M-component and/or Urine M-Component >=90% reduction or <200 mg per 24 hours; or >=50% decrease in difference between involved and uninvolved FLC levels.

Time Frame Duration on study (up to 3 years)
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Len/Cyc/Dex
Hide Arm/Group Description:
Lenalidomide (Len) 15mg daily (days 1-21); Cyclophosphamide (Cyc) 300 mg/m^2 (days 1, 8, 15); Dexamethasone (Dex) 40 mg weekly
Overall Number of Participants Analyzed 35
Measure Type: Number
Unit of Measure: participants
21
2.Secondary Outcome
Title Number of Patients With Organ Response
Hide Description

Organ response was evaluated on the basis of improvement of one or more affected organ; only one parameter was required to satisfy the criteria. Response needed to be maintained for a minimum of 3 months to be considered valid.

Renal response required a 50% reduction in 24-hour urine protein excretion (at least 0.5 g/d) with stable creatinine. Cardiac response required one of >= 2-mm reduction in the interventricular septal (IVS) thickness by echocardiogram, or improvement of ejection fraction by >= 20%, or improvement by 2 NYHA classes without an increase in diuretic use. Hepatic response required either >= 50% decrease in (or normalization of) an initially elevated alkaline phosphatase level or reduction in the size of the liver by at least 2 cm by radiographic determination. Gastrointestinal tract improvement was defined as normalization of a low serum carotene level, or reduction of diarrhea to < 50% of previous movements/day, or decrease in fecal fat excretion by 50%.

Time Frame Duration of study (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Len/Cyc/Dex
Hide Arm/Group Description:
Lenalidomide (Len) 15mg daily (days 1-21); Cyclophosphamide (Cyc) 300 mg/m^2 (days 1, 8, 15); Dexamethasone (Dex) 40 mg weekly
Overall Number of Participants Analyzed 35
Measure Type: Number
Unit of Measure: participants
11
3.Secondary Outcome
Title Number of Participants With Severe Adverse Events
Hide Description Severe adverse events were defined as grade 3 or higher, at least possibly related to study drugs. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.
Time Frame Duration of study (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Len/Cyc/Dex
Hide Arm/Group Description:
Lenalidomide (Len) 15mg daily (days 1-21); Cyclophosphamide (Cyc) 300 mg/m^2 (days 1, 8, 15); Dexamethasone (Dex) 40 mg weekly
Overall Number of Participants Analyzed 35
Measure Type: Number
Unit of Measure: participants
26
4.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description Progression free survival (PFS) was defined as the time from registration to hematologic progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method.
Time Frame Duration of study (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Len/Cyc/Dex
Hide Arm/Group Description:
Lenalidomide (Len) 15mg daily (days 1-21); Cyclophosphamide (Cyc) 300 mg/m^2 (days 1, 8, 15); Dexamethasone (Dex) 40 mg weekly
Overall Number of Participants Analyzed 35
Median (95% Confidence Interval)
Unit of Measure: months
28.3 [1] 
(12.1 to NA)
[1]
The upper limit was not calculable because an insufficient number of participants reached the event at the final time point for assessment
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.
Time Frame Duration of study (up to 3 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Len/Cyc/Dex
Hide Arm/Group Description:
Lenalidomide (Len) 15mg daily (days 1-21); Cyclophosphamide (Cyc) 300 mg/m^2 (days 1, 8, 15); Dexamethasone (Dex) 40 mg weekly
Overall Number of Participants Analyzed 35
Median (95% Confidence Interval)
Unit of Measure: months
37.8 [1] 
(12.3 to NA)
[1]
The upper limit was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Len/Cyc/Dex
Hide Arm/Group Description Dexamethasone (Dex) 40 mg weekly
All-Cause Mortality
Len/Cyc/Dex
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Len/Cyc/Dex
Affected / at Risk (%) # Events
Total   24/35 (68.57%)    
Blood and lymphatic system disorders   
Febrile neutropenia  1  1/35 (2.86%)  1
Hemoglobin decreased  1  4/35 (11.43%)  4
Cardiac disorders   
Atrial fibrillation  1  1/35 (2.86%)  1
Cardiac disorder  1  3/35 (8.57%)  3
Left ventricular failure  1  3/35 (8.57%)  4
Myocardial ischemia  1  1/35 (2.86%)  1
Restrictive cardiomyopathy  1  1/35 (2.86%)  1
Sinus bradycardia  1  1/35 (2.86%)  1
Ventricular arrhythmia  1  2/35 (5.71%)  2
Gastrointestinal disorders   
Abdominal pain  1  2/35 (5.71%)  2
Constipation  1  1/35 (2.86%)  1
Diarrhea  1  3/35 (8.57%)  3
Gastritis  1  1/35 (2.86%)  2
Intestinal necrosis  1  1/35 (2.86%)  1
Lower gastrointestinal hemorrhage  1  2/35 (5.71%)  3
Nausea  1  3/35 (8.57%)  3
Small intestinal obstruction  1  1/35 (2.86%)  1
Vomiting  1  1/35 (2.86%)  1
General disorders   
Edema limbs  1  4/35 (11.43%)  6
Fatigue  1  2/35 (5.71%)  2
Multi-organ failure  1  2/35 (5.71%)  2
Hepatobiliary disorders   
Cholecystitis  1  2/35 (5.71%)  2
Hepatic failure  1  1/35 (2.86%)  1
Infections and infestations   
Colitis, infectious (e.g., Clostridium difficile)  1  1/35 (2.86%)  1
Infection  1  1/35 (2.86%)  1
Pneumonia  1  4/35 (11.43%)  4
Sepsis  1  5/35 (14.29%)  6
Urinary tract infection  1  1/35 (2.86%)  1
Investigations   
Activated partial thromboplastin time prolonged  1  1/35 (2.86%)  1
Alanine aminotransferase increased  1  2/35 (5.71%)  2
Aspartate aminotransferase increased  1  2/35 (5.71%)  2
Bilirubin increased  1  2/35 (5.71%)  2
Creatinine increased  1  3/35 (8.57%)  3
Gamma-glutamyltransferase increased  1  1/35 (2.86%)  1
INR increased  1  1/35 (2.86%)  1
Leukocyte count decreased  1  2/35 (5.71%)  2
Lymphocyte count decreased  1  2/35 (5.71%)  2
Neutrophil count decreased  1  3/35 (8.57%)  4
Platelet count decreased  1  5/35 (14.29%)  5
Metabolism and nutrition disorders   
Alkalosis  1  1/35 (2.86%)  1
Anorexia  1  2/35 (5.71%)  2
Blood glucose increased  1  2/35 (5.71%)  2
Dehydration  1  5/35 (14.29%)  5
Serum albumin decreased  1  2/35 (5.71%)  3
Serum calcium decreased  1  2/35 (5.71%)  2
Serum potassium decreased  1  2/35 (5.71%)  2
Serum sodium decreased  1  3/35 (8.57%)  3
Nervous system disorders   
Peripheral motor neuropathy  1  1/35 (2.86%)  1
Syncope  1  3/35 (8.57%)  4
Psychiatric disorders   
Confusion  1  1/35 (2.86%)  1
Renal and urinary disorders   
Glomerular filtration rate decreased  1  1/35 (2.86%)  1
Renal failure  1  2/35 (5.71%)  2
Respiratory, thoracic and mediastinal disorders   
Atelectasis  1  1/35 (2.86%)  1
Dyspnea  1  4/35 (11.43%)  7
Hypoxia  1  2/35 (5.71%)  2
Pleural effusion  1  3/35 (8.57%)  5
Pneumonitis  1  1/35 (2.86%)  4
Respiratory disorder  1  2/35 (5.71%)  2
Skin and subcutaneous tissue disorders   
Erythema multiforme  1  1/35 (2.86%)  1
Vascular disorders   
Hematoma  1  3/35 (8.57%)  3
Hemorrhage  1  1/35 (2.86%)  1
Hypotension  1  6/35 (17.14%)  7
Thrombosis  1  4/35 (11.43%)  6
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Len/Cyc/Dex
Affected / at Risk (%) # Events
Total   35/35 (100.00%)    
Blood and lymphatic system disorders   
Hemoglobin decreased  1  32/35 (91.43%)  250
Cardiac disorders   
Atrial fibrillation  1  1/35 (2.86%)  1
Atrial flutter  1  1/35 (2.86%)  1
Left ventricular dysfunction  1  1/35 (2.86%)  1
Sinus bradycardia  1  10/35 (28.57%)  17
Endocrine disorders   
Hypothyroidism  1  1/35 (2.86%)  1
Eye disorders   
Cataract  1  1/35 (2.86%)  4
Eye disorder  1  1/35 (2.86%)  1
Gastrointestinal disorders   
Abdominal pain  1  1/35 (2.86%)  1
Constipation  1  21/35 (60.00%)  124
Diarrhea  1  21/35 (60.00%)  90
Ear, nose and throat examination abnormal  1  1/35 (2.86%)  2
Enteritis  1  1/35 (2.86%)  1
Mucositis oral  1  1/35 (2.86%)  1
Nausea  1  2/35 (5.71%)  2
General disorders   
Edema limbs  1  31/35 (88.57%)  188
Fatigue  1  33/35 (94.29%)  320
Fever  1  1/35 (2.86%)  1
Gait abnormal  1  1/35 (2.86%)  1
Infections and infestations   
Bladder infection  1  1/35 (2.86%)  1
Colitis, infectious (e.g., Clostridium difficile)  1  1/35 (2.86%)  1
Gingival infection  1  1/35 (2.86%)  1
Infection  1  1/35 (2.86%)  1
Pneumonia  1  3/35 (8.57%)  3
Sepsis  1  9/35 (25.71%)  11
Sinusitis  1  3/35 (8.57%)  4
Skin infection  1  2/35 (5.71%)  4
Tooth infection  1  1/35 (2.86%)  1
Upper respiratory infection  1  5/35 (14.29%)  5
Injury, poisoning and procedural complications   
Bruising  1  1/35 (2.86%)  1
Wound dehiscence  1  1/35 (2.86%)  1
Investigations   
Alkaline phosphatase increased  1  2/35 (5.71%)  3
Aspartate aminotransferase increased  1  15/35 (42.86%)  45
Creatinine increased  1  18/35 (51.43%)  156
INR increased  1  1/35 (2.86%)  1
Leukocyte count decreased  1  29/35 (82.86%)  180
Lipase increased  1  1/35 (2.86%)  1
Lymphocyte count decreased  1  2/35 (5.71%)  6
Neutrophil count decreased  1  21/35 (60.00%)  128
Platelet count decreased  1  24/35 (68.57%)  207
Metabolism and nutrition disorders   
Anorexia  1  1/35 (2.86%)  1
Blood uric acid increased  1  1/35 (2.86%)  1
Serum albumin decreased  1  2/35 (5.71%)  3
Serum calcium decreased  1  2/35 (5.71%)  3
Serum calcium increased  1  1/35 (2.86%)  1
Serum potassium decreased  1  1/35 (2.86%)  1
Musculoskeletal and connective tissue disorders   
Bone pain  1  1/35 (2.86%)  2
Muscle weakness  1  8/35 (22.86%)  10
Muscle weakness lower limb  1  2/35 (5.71%)  2
Myalgia  1  2/35 (5.71%)  2
Nervous system disorders   
Cognitive disturbance  1  10/35 (28.57%)  56
Memory impairment  1  1/35 (2.86%)  1
Peripheral motor neuropathy  1  9/35 (25.71%)  52
Peripheral sensory neuropathy  1  20/35 (57.14%)  176
Syncope  1  4/35 (11.43%)  6
Psychiatric disorders   
Anxiety  1  2/35 (5.71%)  3
Depression  1  3/35 (8.57%)  8
Insomnia  1  10/35 (28.57%)  22
Renal and urinary disorders   
Cystitis  1  6/35 (17.14%)  7
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  1/35 (2.86%)  1
Pleural effusion  1  2/35 (5.71%)  5
Skin and subcutaneous tissue disorders   
Rash desquamating  1  13/35 (37.14%)  29
Vascular disorders   
Hypertension  1  1/35 (2.86%)  1
Hypotension  1  1/35 (2.86%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10
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: Dr. Shaji Kumar
Organization: Mayo Clinic
EMail: kumar.shaji@mayo.edu
Layout table for additonal information
Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00564889     History of Changes
Other Study ID Numbers: MC0685
P30CA015083 ( U.S. NIH Grant/Contract )
MC0685 ( Other Identifier: Mayo Clinic Cancer Center )
NCI-2010-01954 ( Other Identifier: NCI CTRP )
06-005711 ( Other Identifier: Mayo Clinic IRB )
First Submitted: November 28, 2007
First Posted: November 29, 2007
Results First Submitted: July 19, 2011
Results First Posted: August 12, 2011
Last Update Posted: May 14, 2013