Trial Outcomes & Findings for Lenalidomide, Cyclophosphamide, and Dexamethasone in Treating Patients With Primary Systemic Amyloidosis (NCT NCT00564889)
NCT ID: NCT00564889
Last Updated: 2013-05-14
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
35 participants
Primary outcome timeframe
Duration on study (up to 3 years)
Results posted on
2013-05-14
Participant Flow
Thirty-five(35) participants were recruited between December 2007 and November 2008 at Mayo Clinic.
Participant milestones
| Measure |
Len/Cyc/Dex
Lenalidomide (Len) 15mg daily (days 1-21)
Cyclophosphamide (Cyc) 300 mg/m\^2 (days 1, 8, 15)
Dexamethasone (Dex) 40 mg weekly
|
|---|---|
|
Overall Study
STARTED
|
35
|
|
Overall Study
COMPLETED
|
6
|
|
Overall Study
NOT COMPLETED
|
29
|
Reasons for withdrawal
| Measure |
Len/Cyc/Dex
Lenalidomide (Len) 15mg daily (days 1-21)
Cyclophosphamide (Cyc) 300 mg/m\^2 (days 1, 8, 15)
Dexamethasone (Dex) 40 mg weekly
|
|---|---|
|
Overall Study
Death
|
7
|
|
Overall Study
Adverse Event
|
12
|
|
Overall Study
Alternative treatment
|
3
|
|
Overall Study
Disease progression
|
3
|
|
Overall Study
Other, not specified
|
4
|
Baseline Characteristics
Lenalidomide, Cyclophosphamide, and Dexamethasone in Treating Patients With Primary Systemic Amyloidosis
Baseline characteristics by cohort
| Measure |
Len/Cyc/Dex
n=35 Participants
Lenalidomide (Len) 15mg daily (days 1-21); Cyclophosphamide (Cyc) 300 mg/m\^2 (days 1, 8, 15); Dexamethasone (Dex) 40 mg weekly
|
|---|---|
|
Age Continuous
|
64 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
35 participants
n=5 Participants
|
|
Received Previous Treatment
Yes
|
11 participants
n=5 Participants
|
|
Received Previous Treatment
No
|
24 participants
n=5 Participants
|
|
Had a Prior Stem Cell Transplant
Yes
|
7 participants
n=5 Participants
|
|
Had a Prior Stem Cell Transplant
No
|
28 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Duration on study (up to 3 years)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.
Outcome measures
| Measure |
Len/Cyc/Dex
n=35 Participants
Lenalidomide (Len) 15mg daily (days 1-21); Cyclophosphamide (Cyc) 300 mg/m\^2 (days 1, 8, 15); Dexamethasone (Dex) 40 mg weekly
|
|---|---|
|
Number of Participants Who Achieved a Confirmed Response Defined as a Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR)
|
21 participants
|
SECONDARY outcome
Timeframe: Duration of study (up to 3 years)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%.
Outcome measures
| Measure |
Len/Cyc/Dex
n=35 Participants
Lenalidomide (Len) 15mg daily (days 1-21); Cyclophosphamide (Cyc) 300 mg/m\^2 (days 1, 8, 15); Dexamethasone (Dex) 40 mg weekly
|
|---|---|
|
Number of Patients With Organ Response
|
11 participants
|
SECONDARY outcome
Timeframe: Duration of study (up to 3 years)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.
Outcome measures
| Measure |
Len/Cyc/Dex
n=35 Participants
Lenalidomide (Len) 15mg daily (days 1-21); Cyclophosphamide (Cyc) 300 mg/m\^2 (days 1, 8, 15); Dexamethasone (Dex) 40 mg weekly
|
|---|---|
|
Number of Participants With Severe Adverse Events
|
26 participants
|
SECONDARY outcome
Timeframe: Duration of study (up to 3 years)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.
Outcome measures
| Measure |
Len/Cyc/Dex
n=35 Participants
Lenalidomide (Len) 15mg daily (days 1-21); Cyclophosphamide (Cyc) 300 mg/m\^2 (days 1, 8, 15); Dexamethasone (Dex) 40 mg weekly
|
|---|---|
|
Progression Free Survival (PFS)
|
28.3 months
Interval 12.1 to
The upper limit was not calculable because an insufficient number of participants reached the event at the final time point for assessment
|
SECONDARY outcome
Timeframe: Duration of study (up to 3 years)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.
Outcome measures
| Measure |
Len/Cyc/Dex
n=35 Participants
Lenalidomide (Len) 15mg daily (days 1-21); Cyclophosphamide (Cyc) 300 mg/m\^2 (days 1, 8, 15); Dexamethasone (Dex) 40 mg weekly
|
|---|---|
|
Overall Survival (OS)
|
37.8 months
Interval 12.3 to
The upper limit was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
Adverse Events
Len/Cyc/Dex
Serious events: 24 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Len/Cyc/Dex
n=35 participants at risk
Dexamethasone (Dex) 40 mg weekly
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.9%
1/35 • Number of events 1
|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
11.4%
4/35 • Number of events 4
|
|
Cardiac disorders
Atrial fibrillation
|
2.9%
1/35 • Number of events 1
|
|
Cardiac disorders
Cardiac disorder
|
8.6%
3/35 • Number of events 3
|
|
Cardiac disorders
Left ventricular failure
|
8.6%
3/35 • Number of events 4
|
|
Cardiac disorders
Myocardial ischemia
|
2.9%
1/35 • Number of events 1
|
|
Cardiac disorders
Restrictive cardiomyopathy
|
2.9%
1/35 • Number of events 1
|
|
Cardiac disorders
Sinus bradycardia
|
2.9%
1/35 • Number of events 1
|
|
Cardiac disorders
Ventricular arrhythmia
|
5.7%
2/35 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain
|
5.7%
2/35 • Number of events 2
|
|
Gastrointestinal disorders
Constipation
|
2.9%
1/35 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
8.6%
3/35 • Number of events 3
|
|
Gastrointestinal disorders
Gastritis
|
2.9%
1/35 • Number of events 2
|
|
Gastrointestinal disorders
Intestinal necrosis
|
2.9%
1/35 • Number of events 1
|
|
Gastrointestinal disorders
Lower gastrointestinal hemorrhage
|
5.7%
2/35 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
8.6%
3/35 • Number of events 3
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
2.9%
1/35 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
2.9%
1/35 • Number of events 1
|
|
General disorders
Edema limbs
|
11.4%
4/35 • Number of events 6
|
|
General disorders
Fatigue
|
5.7%
2/35 • Number of events 2
|
|
General disorders
Multi-organ failure
|
5.7%
2/35 • Number of events 2
|
|
Hepatobiliary disorders
Cholecystitis
|
5.7%
2/35 • Number of events 2
|
|
Hepatobiliary disorders
Hepatic failure
|
2.9%
1/35 • Number of events 1
|
|
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)
|
2.9%
1/35 • Number of events 1
|
|
Infections and infestations
Infection
|
2.9%
1/35 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
11.4%
4/35 • Number of events 4
|
|
Infections and infestations
Sepsis
|
14.3%
5/35 • Number of events 6
|
|
Infections and infestations
Urinary tract infection
|
2.9%
1/35 • Number of events 1
|
|
Investigations
Activated partial thromboplastin time prolonged
|
2.9%
1/35 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
5.7%
2/35 • Number of events 2
|
|
Investigations
Aspartate aminotransferase increased
|
5.7%
2/35 • Number of events 2
|
|
Investigations
Bilirubin increased
|
5.7%
2/35 • Number of events 2
|
|
Investigations
Creatinine increased
|
8.6%
3/35 • Number of events 3
|
|
Investigations
Gamma-glutamyltransferase increased
|
2.9%
1/35 • Number of events 1
|
|
Investigations
INR increased
|
2.9%
1/35 • Number of events 1
|
|
Investigations
Leukocyte count decreased
|
5.7%
2/35 • Number of events 2
|
|
Investigations
Lymphocyte count decreased
|
5.7%
2/35 • Number of events 2
|
|
Investigations
Neutrophil count decreased
|
8.6%
3/35 • Number of events 4
|
|
Investigations
Platelet count decreased
|
14.3%
5/35 • Number of events 5
|
|
Metabolism and nutrition disorders
Alkalosis
|
2.9%
1/35 • Number of events 1
|
|
Metabolism and nutrition disorders
Anorexia
|
5.7%
2/35 • Number of events 2
|
|
Metabolism and nutrition disorders
Blood glucose increased
|
5.7%
2/35 • Number of events 2
|
|
Metabolism and nutrition disorders
Dehydration
|
14.3%
5/35 • Number of events 5
|
|
Metabolism and nutrition disorders
Serum albumin decreased
|
5.7%
2/35 • Number of events 3
|
|
Metabolism and nutrition disorders
Serum calcium decreased
|
5.7%
2/35 • Number of events 2
|
|
Metabolism and nutrition disorders
Serum potassium decreased
|
5.7%
2/35 • Number of events 2
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
8.6%
3/35 • Number of events 3
|
|
Nervous system disorders
Peripheral motor neuropathy
|
2.9%
1/35 • Number of events 1
|
|
Nervous system disorders
Syncope
|
8.6%
3/35 • Number of events 4
|
|
Psychiatric disorders
Confusion
|
2.9%
1/35 • Number of events 1
|
|
Renal and urinary disorders
Glomerular filtration rate decreased
|
2.9%
1/35 • Number of events 1
|
|
Renal and urinary disorders
Renal failure
|
5.7%
2/35 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
2.9%
1/35 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
11.4%
4/35 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
5.7%
2/35 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
8.6%
3/35 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
2.9%
1/35 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
5.7%
2/35 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
2.9%
1/35 • Number of events 1
|
|
Vascular disorders
Hematoma
|
8.6%
3/35 • Number of events 3
|
|
Vascular disorders
Hemorrhage
|
2.9%
1/35 • Number of events 1
|
|
Vascular disorders
Hypotension
|
17.1%
6/35 • Number of events 7
|
|
Vascular disorders
Thrombosis
|
11.4%
4/35 • Number of events 6
|
Other adverse events
| Measure |
Len/Cyc/Dex
n=35 participants at risk
Dexamethasone (Dex) 40 mg weekly
|
|---|---|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
91.4%
32/35 • Number of events 250
|
|
Cardiac disorders
Atrial fibrillation
|
2.9%
1/35 • Number of events 1
|
|
Cardiac disorders
Atrial flutter
|
2.9%
1/35 • Number of events 1
|
|
Cardiac disorders
Left ventricular dysfunction
|
2.9%
1/35 • Number of events 1
|
|
Cardiac disorders
Sinus bradycardia
|
28.6%
10/35 • Number of events 17
|
|
Endocrine disorders
Hypothyroidism
|
2.9%
1/35 • Number of events 1
|
|
Eye disorders
Cataract
|
2.9%
1/35 • Number of events 4
|
|
Eye disorders
Eye disorder
|
2.9%
1/35 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
2.9%
1/35 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
60.0%
21/35 • Number of events 124
|
|
Gastrointestinal disorders
Diarrhea
|
60.0%
21/35 • Number of events 90
|
|
Gastrointestinal disorders
Ear, nose and throat examination abnormal
|
2.9%
1/35 • Number of events 2
|
|
Gastrointestinal disorders
Enteritis
|
2.9%
1/35 • Number of events 1
|
|
Gastrointestinal disorders
Mucositis oral
|
2.9%
1/35 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
5.7%
2/35 • Number of events 2
|
|
General disorders
Edema limbs
|
88.6%
31/35 • Number of events 188
|
|
General disorders
Fatigue
|
94.3%
33/35 • Number of events 320
|
|
General disorders
Fever
|
2.9%
1/35 • Number of events 1
|
|
General disorders
Gait abnormal
|
2.9%
1/35 • Number of events 1
|
|
Infections and infestations
Bladder infection
|
2.9%
1/35 • Number of events 1
|
|
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)
|
2.9%
1/35 • Number of events 1
|
|
Infections and infestations
Gingival infection
|
2.9%
1/35 • Number of events 1
|
|
Infections and infestations
Infection
|
2.9%
1/35 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
8.6%
3/35 • Number of events 3
|
|
Infections and infestations
Sepsis
|
25.7%
9/35 • Number of events 11
|
|
Infections and infestations
Sinusitis
|
8.6%
3/35 • Number of events 4
|
|
Infections and infestations
Skin infection
|
5.7%
2/35 • Number of events 4
|
|
Infections and infestations
Tooth infection
|
2.9%
1/35 • Number of events 1
|
|
Infections and infestations
Upper respiratory infection
|
14.3%
5/35 • Number of events 5
|
|
Injury, poisoning and procedural complications
Bruising
|
2.9%
1/35 • Number of events 1
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
2.9%
1/35 • Number of events 1
|
|
Investigations
Alkaline phosphatase increased
|
5.7%
2/35 • Number of events 3
|
|
Investigations
Aspartate aminotransferase increased
|
42.9%
15/35 • Number of events 45
|
|
Investigations
Creatinine increased
|
51.4%
18/35 • Number of events 156
|
|
Investigations
INR increased
|
2.9%
1/35 • Number of events 1
|
|
Investigations
Leukocyte count decreased
|
82.9%
29/35 • Number of events 180
|
|
Investigations
Lipase increased
|
2.9%
1/35 • Number of events 1
|
|
Investigations
Lymphocyte count decreased
|
5.7%
2/35 • Number of events 6
|
|
Investigations
Neutrophil count decreased
|
60.0%
21/35 • Number of events 128
|
|
Investigations
Platelet count decreased
|
68.6%
24/35 • Number of events 207
|
|
Metabolism and nutrition disorders
Anorexia
|
2.9%
1/35 • Number of events 1
|
|
Metabolism and nutrition disorders
Blood uric acid increased
|
2.9%
1/35 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum albumin decreased
|
5.7%
2/35 • Number of events 3
|
|
Metabolism and nutrition disorders
Serum calcium decreased
|
5.7%
2/35 • Number of events 3
|
|
Metabolism and nutrition disorders
Serum calcium increased
|
2.9%
1/35 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum potassium decreased
|
2.9%
1/35 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
2.9%
1/35 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
22.9%
8/35 • Number of events 10
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
5.7%
2/35 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.7%
2/35 • Number of events 2
|
|
Nervous system disorders
Cognitive disturbance
|
28.6%
10/35 • Number of events 56
|
|
Nervous system disorders
Memory impairment
|
2.9%
1/35 • Number of events 1
|
|
Nervous system disorders
Peripheral motor neuropathy
|
25.7%
9/35 • Number of events 52
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
57.1%
20/35 • Number of events 176
|
|
Nervous system disorders
Syncope
|
11.4%
4/35 • Number of events 6
|
|
Psychiatric disorders
Anxiety
|
5.7%
2/35 • Number of events 3
|
|
Psychiatric disorders
Depression
|
8.6%
3/35 • Number of events 8
|
|
Psychiatric disorders
Insomnia
|
28.6%
10/35 • Number of events 22
|
|
Renal and urinary disorders
Cystitis
|
17.1%
6/35 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
2.9%
1/35 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
5.7%
2/35 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
37.1%
13/35 • Number of events 29
|
|
Vascular disorders
Hypertension
|
2.9%
1/35 • Number of events 1
|
|
Vascular disorders
Hypotension
|
2.9%
1/35 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place