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Trial record 6 of 846 for:    LENALIDOMIDE AND Angiogenesis

Azacitidine + Lenalidomide Combo in the Elderly With Previously Treated AML & High-Risk MDS

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ClinicalTrials.gov Identifier: NCT01442714
Recruitment Status : Terminated (Lack of efficacy - Inability to meet the primary response endpoint)
First Posted : September 28, 2011
Results First Posted : January 3, 2018
Last Update Posted : January 3, 2018
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Bruno C. Medeiros, Stanford University

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Leukemia
Acute Myeloid Leukemia (AML)
Myelodysplastic Syndromes (MDS)
Interventions Drug: Azacitidine
Drug: Lenalidomide
Enrollment 33
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Azacitidine Plus Lenalidomide
Hide Arm/Group Description

Patients will receive a single dose of azacitidine 75mg/m2 SC/IV on d 1 to 7, followed by lenalidomide 50mg PO daily on d 8 to 28 of a 42-day cycle.

Azacitidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death

Lenalidomide: Lenalidomide has been used to successfully treat both inflammatory disorders and cancers. In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of angiogenesis, and immunomodulatory role. In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory

Period Title: Overall Study
Started 33
Completed 21
Not Completed 12
Reason Not Completed
Death             11
Withdrawal by Subject             1
Arm/Group Title Azacitidine Plus Lenalidomide
Hide Arm/Group Description Azacitidine + Lenalidomide Combo
Overall Number of Baseline Participants 33
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants
<=18 years
0
   0.0%
Between 18 and 65 years
3
   9.1%
>=65 years
30
  90.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants
Female
14
  42.4%
Male
19
  57.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   3.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
   6.1%
White
28
  84.8%
More than one race
0
   0.0%
Unknown or Not Reported
2
   6.1%
Eastern Cooperative Oncology Group Performance Status (ECOG PS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants
0
24
  72.7%
1
6
  18.2%
2
3
   9.1%
Not eligible
5
  15.2%
[1]
Measure Description:

ECOG PS Scale:

0 Fully active, able to carry on all pre-disease performance without restriction.

  1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work.
  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.
  3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
  4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
  5. Dead
1.Primary Outcome
Title Overall Response Rate (ORR)
Hide Description Overall response rate was defined as the sum of Complete Response (CR) + CR with incomplete count recovery (CRi) + Partial Response (PR).
Time Frame 203 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Azacitidine Plus Lenalidomide
Hide Arm/Group Description:
Acute myeloid leukemia (AML) ORR was defined as the sum of Complete Response (CR) + CR with incomplete count recovery (CRi) + Partial Response (PR): (CR + CRi + PR)
Overall Number of Participants Analyzed 33
Measure Type: Count of Participants
Unit of Measure: Participants
5
  15.2%
2.Secondary Outcome
Title Median Duration of Response
Hide Description The median duration of response was defined by the median duration of response for participants with Complete Response (CR); CR with incomplete count recovery (CRi); or Partial Response (PR).
Time Frame 203 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Azacitidine Plus Lenalidomide
Hide Arm/Group Description:

Patients will receive a single dose of azacitidine 75mg/m2 SC/IV on d 1-7, followed by lenalidomide 50mg PO daily on d 8-28 of a 42-day cycle.

Azacitidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death. Lenalidomide: Lenalidomide has been used to successfully treat both inflammatory disorders and cancers. In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of angiogenesis, and immunomodulatory role. In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory.

Overall Number of Participants Analyzed 5
Median (95% Confidence Interval)
Unit of Measure: days
118
(56.48 to 349.5)
3.Secondary Outcome
Title Overall Survival
Hide Description Survival was measured from the 1st day of azacitidine treatment to death from any cause.
Time Frame 462 Days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Azacitidine Plus Lenalidomide
Hide Arm/Group Description:

Patients will receive a single dose of azacitidine 75mg/m2 SC/IV on d 1 to 7, followed by lenalidomide 50mg PO daily on d 8 to 28 of a 42-day cycle.

Azacitidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death

Lenalidomide: Lenalidomide has been used to successfully treat both inflammatory disorders and cancers. In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of angiogenesis, and immunomodulatory role. In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory

Overall Number of Participants Analyzed 33
Median (95% Confidence Interval)
Unit of Measure: months
5
(3.7 to 8.6)
Time Frame 16 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Azacitidine Plus Lenalidomide
Hide Arm/Group Description

Patients will receive a single dose of azacitidine 75mg/m2 SC/IV on d 1 to 7, followed by lenalidomide 50mg PO daily on d 8 to 28 of a 42-day cycle.

Azacitidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death

Lenalidomide: Lenalidomide has been used to successfully treat both inflammatory disorders and cancers. In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of angiogenesis, and immunomodulatory role. In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory.

All-Cause Mortality
Azacitidine Plus Lenalidomide
Affected / at Risk (%)
Total   30/33 (90.91%)    
Show Serious Adverse Events Hide Serious Adverse Events
Azacitidine Plus Lenalidomide
Affected / at Risk (%) # Events
Total   33/33 (100.00%)    
Blood and lymphatic system disorders   
Pancytopenia * 1  2/33 (6.06%) 
Disseminated Intravascular Coagulation * 1 [1]  1/33 (3.03%) 
Cardiac disorders   
Cardiac complications * 1 [2]  2/33 (6.06%) 
Gastrointestinal disorders   
Diarrhea * 1  1/33 (3.03%) 
Gastrointestinal Bleeding * 1  1/33 (3.03%) 
Colon Volvulus * 1  1/33 (3.03%) 
Vomitting * 1  1/33 (3.03%) 
General disorders   
Cellulitis * 1 [3]  2/33 (6.06%) 
Graft vs host disease (GvHD) * 1  1/33 (3.03%) 
Rigors secondary to fever * 1  1/33 (3.03%) 
Fever * 1  2/33 (6.06%) 
Infections and infestations   
Neutropenic fever * 1 [4]  25/33 (75.76%) 
Sepsis * 1 [5]  2/33 (6.06%) 
Progressive disease * 1 [6]  2/33 (6.06%) 
Neck complications * 1 [7]  2/33 (6.06%) 
Metabolism and nutrition disorders   
Hyperglycemia * 1  1/33 (3.03%) 
Musculoskeletal and connective tissue disorders   
Neck pain and stiffness * 1  1/33 (3.03%) 
Generalized weakness * 1 [8]  2/33 (6.06%) 
Body pain * 1 [9]  2/33 (6.06%) 
Hypoxia * 1  1/33 (3.03%) 
Nervous system disorders   
Encephalopathy * 1  1/33 (3.03%) 
Respiratory, thoracic and mediastinal disorders   
Respiratory complications * 1 [10]  8/33 (24.24%) 
Death on study * 1  11/33 (33.33%) 
Skin and subcutaneous tissue disorders   
Skin infections * 1 [11]  2/33 (6.06%) 
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
[1]
(DIC)
[2]
Including: atrial flutters, asystole
[3]
right groin and facial (periorbital)
[4]
Including: Neutropenia
[5]
including: sepsis with acute dysfunction
[6]
worsening AML
[7]
Including: abscess, pain and stiffness
[8]
lethargic
[9]
back, abdomen
[10]
Including: dyspnea, pneumonia, aspiration pneumonitis
[11]
sweet syndrome
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Azacitidine Plus Lenalidomide
Affected / at Risk (%) # Events
Total   33/33 (100.00%)    
Blood and lymphatic system disorders   
Epistaxis * 1  1/33 (3.03%)  1
hyperglycemic * 1  1/33 (3.03%)  1
Hypotensive * 1  1/33 (3.03%)  1
Hypertrophy of her gums * 1  1/33 (3.03%)  1
Significant Cytopenias * 1  1/33 (3.03%)  1
Cardiac disorders   
Left carotid * 1 [1]  2/33 (6.06%)  2
Tachycardiac * 1  1/33 (3.03%)  1
episodes of chest pressure * 1 [2]  1/33 (3.03%)  1
Unspecified arrhythmia * 1  1/33 (3.03%)  1
Eye disorders   
Redness and itching of eyes * 1  1/33 (3.03%)  1
Sudden loss of central vision * 1  1/33 (3.03%)  1
Gastrointestinal disorders   
Decreased appetite * 1  1/33 (3.03%)  1
epigastic pain after eating * 1 [2]  1/33 (3.03%)  1
General disorders   
Dehydration * 1  1/33 (3.03%)  1
Fall * 1  1/33 (3.03%)  1
Fever * 1  1/33 (3.03%)  1
fracture of left fibula * 1  1/33 (3.03%)  1
Frontal headache * 1  1/33 (3.03%)  1
Left hip injury * 1  1/33 (3.03%)  1
Left leg pain * 1 [3]  3/33 (9.09%)  3
Mild erythema at abdominal injection site * 1  1/33 (3.03%)  1
Mouth soures/ thrush * 1 [4]  4/33 (12.12%)  4
Night sweat * 1  2/33 (6.06%)  2
stress incontinence * 1  1/33 (3.03%)  1
Swollen Knee * 1  1/33 (3.03%)  1
tender facial skin * 1  1/33 (3.03%)  1
weight loss * 1  1/33 (3.03%)  1
Infections and infestations   
erythema and conjunctival injection of right eye * 1 [5]  2/33 (6.06%)  2
erythematous lesions at injection site at abdomen * 1  1/33 (3.03%)  1
Musculoskeletal and connective tissue disorders   
Edema * 1 [6]  2/33 (6.06%)  2
back pain * 1  1/33 (3.03%)  1
Cramps * 1 [7]  2/33 (6.06%)  2
Tremors * 1  2/33 (6.06%)  2
Nervous system disorders   
Neuropathy * 1 [8]  2/33 (6.06%) 
Renal and urinary disorders   
Difficulty urinating * 1  1/33 (3.03%)  1
Elevated LFT (AST>AST) * 1  1/33 (3.03%)  1
Respiratory, thoracic and mediastinal disorders   
apneic * 1  2/33 (6.06%)  2
Crackles at right base of lung * 1  1/33 (3.03%)  1
cough * 1  3/33 (9.09%)  3
Fungal pneumonia * 1  2/33 (6.06%)  2
Rhinorrhea * 1  2/33 (6.06%)  2
Hoarse voice * 1  3/33 (9.09%)  3
left thyroid nodule * 1  1/33 (3.03%)  1
Nose bleeds * 1  2/33 (6.06%)  2
Open sore of lower lip * 1  1/33 (3.03%)  1
Sore throat * 1  1/33 (3.03%)  1
sore tongue * 1  2/33 (6.06%)  2
Taste changes * 1  1/33 (3.03%)  1
Allergies * 1  1/33 (3.03%)  1
Skin and subcutaneous tissue disorders   
skin nodules * 1  2/33 (6.06%)  2
Ecchymoses on site injections * 1  1/33 (3.03%)  1
Large bruise * 1 [9]  1/33 (3.03%)  1
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
[1]
artery stenosis and endarterectomy
[2]
intermittent
[3]
including sciatica and cramping
[4]
including oral ulcer
[5]
including hemorrhaging and swelling
[6]
on lower extremities
[7]
Upper and lower extremities
[8]
In feet and fingers. Includes Peripheral Neuropathy.
[9]
on right tight
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. Bruno Medeiros
Organization: Stanford University
Phone: 650-723-5007
EMail: brunom@stanford.edu
Layout table for additonal information
Responsible Party: Bruno C. Medeiros, Stanford University
ClinicalTrials.gov Identifier: NCT01442714     History of Changes
Other Study ID Numbers: IRB-21686
SU-08122011-8268 ( Other Identifier: Stanford University )
HEM0022 ( Other Identifier: OnCore Number )
VIREL2 ( Other Identifier: Stanford University )
First Submitted: September 23, 2011
First Posted: September 28, 2011
Results First Submitted: October 17, 2016
Results First Posted: January 3, 2018
Last Update Posted: January 3, 2018