Lenalidomide and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndromes

• Sponsor: Mikkael Sekeres MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT00352001
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 37
• Locations: 3
• Arm: 1
• Duration (Months): 64
• Patients Per Site: 12.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Lenalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Lenalidomide may also stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Azacitidine may also cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving lenalidomide together with azacitidine may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of lenalidomide and azacitidine in treating patients with advanced myelodysplastic syndromes.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Myelodysplastic Syndromes	Drug: azacitidine; Drug: lenalidomide	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and dose-limiting toxicity of lenalidomide and azacitidine in patients with advanced myelodysplastic syndromes (MDS).

Secondary

• Review clinical outcomes, as defined by the International Working Group criteria, in patients treated with this regimen.

• Determine time to transformation to acute myeloid leukemia or death in patients treated with this regimen.

• Determine time to relapse after achieving complete or partial remission in patients treated with this regimen.

• Determine time to disease progression in patients treated with this regimen.

• Determine the effect of this regimen on hematologic status (including peripheral blood counts and the need for platelet and/or red blood cell transfusions) in these patients.

OUTLINE: This is an open-label, multicenter, dose-escalation study.

Patients receive oral lenalidomide once daily on days 1-14 or days 1-21 and azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses and/or increasing dosing frequencies of lenalidomide and azacitidine until the maximum tolerated dose (MTD) is determined or the sixth dose level is reached, whichever occurs first. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course of therapy.

After completion of study treatment, patients are followed annually.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of Revlimid (Lenalidomide) in Combination With Vidaza (Azacitidine) in Patients With Advanced Myelodysplastic Syndrome (MDS)
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Lenalidomide and Azacitidine

Drug: azacitidine; Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.; Other Names: Vidaza® ; Drug: lenalidomide; Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.; Other Names: Revlimid®

Outcome Measures

Primary Outcome Measures

1. PHASE I: Maximum Tolerated Dose of Azacitidine [After 1 courses (1 months)]

   Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard "3+3" design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here.

2. PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate) [After 4 courses (4 months)]

   For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement. Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones. Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality. Hematologic Improvement (HI) is defined as: red blood cell increase of >=1.5g/dL, a platelet response of >=30X10^9/L or by at least 100% for values starting <20X10^9/L, or a neutrophil response of at least 100% and absolute increase of >0.5X10^9/L

3. PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate) [After 7 courses (months)]

   For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement) Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones. Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality. Hematologic Improvement (HI) is defined as: red blood cell increase of >=1.5g/dL, a platelet response of >=30X10^9/L or by at least 100% for values starting <20X10^9/L, or a neutrophil response of at least 100% and absolute increase of >0.5X10^9/L

4. PHASE I: Maximum Tolerated Dose of Lenalidomide [After 1 courses (1 months)]

   Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard "3+3" design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here.

Secondary Outcome Measures

1. Time to Transformation to Acute Myeloid Leukemia or Death [After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months]

   Time (in months) patients took to evolve to myeloid leukemia or death after achieving a complete response using the RECIST criteria

2. Time to Relapse After Achieving Complete Response [After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months]

3. Number of Patients That Experience Grade 3 or 4 Treatment Related Non-hematologic Adverse Events [After 7 months]

4. Overall Survival Among Patients With Complete Response [After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months]

   Time (in months) patients who achieved a complete response using the RECIST criteria were alive on study

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of myelodysplastic syndromes (MDS) meeting one of the following criteria:

• French-American-British histological classification criteria

• Refractory anemia with excess blasts (RAEB), defined as 5-19% myeloblasts in the bone marrow

• Patients with 20% blasts are considered to have acute myeloid leukemia (per WHO classification system) and are therefore excluded in this study

• Chronic myelomonocytic leukemia (CMML), defined as 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood

• WHO histological classification criteria

• RAEB-1, defined as 5-9% myeloblasts in the bone marrow

• RAEB-2, defined as 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood

• CMML-2, defined as 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood

• International Prognostic Scoring System (IPSS) score of intermediate 2 (1.5-2.0 points based on karyotype, cytopenias, and bone marrow blast percentage) or high (≥ 2.5 points), in the setting of ≥ 5% myeloblasts

• Considered ineligible for bone marrow transplantation as first-line therapy

PATIENT CHARACTERISTICS:

• Life expectancy ≥ 3 months

• ECOG performance status 0-2

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective double-method contraception for 4 weeks before, during, and for 4 weeks after completion of study treatment

• No serious medical condition, laboratory abnormality, or psychiatric illness that, in the opinion of the treating physician, would preclude study participation or preclude giving informed consent

• No preexisting neurotoxicity or neuropathy ≥ grade 2

• No rash or prior hypersensitivity or allergic reaction ≥ grade 3 to thalidomide

• Creatinine ≤ 2.0 mg/dL

• AST and ALT ≤ 2.0 times upper limit of normal

• Bilirubin ≤ 2 mg/dL

• Platelet count ≥ 50,000/mm^3

• Absolute neutrophil count ≥ 500/mm^3

• No other malignancy within the past 3 years except curatively treated carcinoma in situ of the cervix or nonmelanoma skin cancer

• No history of thromboembolic event or other condition requiring use of anticoagulation with warfarin or low molecular-weight heparin

• No known or suspected hypersensitivity to azacitidine or mannitol

PRIOR CONCURRENT THERAPY:

• More than 28 days since prior and no other concurrent investigational agents for MDS

• More than 28 days since prior approved therapy for MDS

• More than 14 days since prior growth factors

• More than 28 days since prior and no concurrent supraphysiologic doses (equivalent to

10 mg/day of prednisone) of corticosteroids

• More than 12 months since prior radiotherapy, chemotherapy, or cytotoxic therapy for treatment of conditions other than MDS

• No prior lenalidomide or azacitidine

• No prior stem cell or bone marrow transplantation

• No concurrent androgens, epoetin alfa, or chemotherapy for MDS

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California at Los Angeles	Los Angeles	California	United States	90095-1781
2	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida	United States	33612-9497
3	Cleveland Clinic Taussig Cancer Instititute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Mikkael Sekeres MD
• National Cancer Institute (NCI)

Investigators

• Study Chair: Mikkael A. Sekeres, MD, MS, The Cleveland Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mikkael Sekeres MD, Principal Investigator, Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00352001
• Other Study ID Numbers: CASE17Z05; P30CA016042; UCLA-0511032-01; UCLA-RDN-5405; UCLA-05011032-01; CASE17Z05; NCT00326846
• First Posted: Jul 14, 2006
• Last Update Posted: Sep 19, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Mikkael Sekeres MD, Principal Investigator, Case Comprehensive Cancer Center: refractory anemia with excess blasts; previously treated myelodysplastic syndromes; chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; secondary myelodysplastic syndromes
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome; Lenalidomide; Azacitidine

Study Results

Participant Flow

Arm/Group Title	Lenalidomide and Azacitidine
Arm/Group Description	azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity. lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.
Period Title: Overall Study
STARTED	37
Azacitidine 75mg/Lenalidomide 5mg-14 Day	3
Azacitidine 75mg/Lenalidomide 5mg-21 Day	3
Azacitidine 75mg/Lenalidomide 10mg-14day	3
COMPLETED	37
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Lenalidomide and Azacitidine
Arm/Group Description	azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity. lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.
Overall Participants	37
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	76.5
Sex: Female, Male (Count of Participants)
Female	13 35.1%
Male	24 64.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.4%
Not Hispanic or Latino	28 75.7%
Unknown or Not Reported	7 18.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 2.7%
White	36 97.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	37 100%

Outcome Measures

1. Primary Outcome

Title	PHASE I: Maximum Tolerated Dose of Azacitidine
Description	Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard "3+3" design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here.
Time Frame	After 1 courses (1 months)

Outcome Measure Data

Analysis Population Description

Participants in Phase I

Arm/Group Title	Lenalidomide and Azacitidine
Arm/Group Description	azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity. lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.
Measure Participants	18
Number [mg/m2 subcutaneously for 5 days]	75

2. Primary Outcome

Title	PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)
Description	For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement. Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones. Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality. Hematologic Improvement (HI) is defined as: red blood cell increase of >=1.5g/dL, a platelet response of >=30X10^9/L or by at least 100% for values starting <20X10^9/L, or a neutrophil response of at least 100% and absolute increase of >0.5X10^9/L
Time Frame	After 4 courses (4 months)

Outcome Measure Data

Analysis Population Description

Intention to Treat

Arm/Group Title	Lenalidomide and Azacitidine
Arm/Group Description	azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity. lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.
Measure Participants	37
Number [participants]	26 70.3%

3. Primary Outcome

Title	PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)
Description	For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement) Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones. Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality. Hematologic Improvement (HI) is defined as: red blood cell increase of >=1.5g/dL, a platelet response of >=30X10^9/L or by at least 100% for values starting <20X10^9/L, or a neutrophil response of at least 100% and absolute increase of >0.5X10^9/L
Time Frame	After 7 courses (months)

Outcome Measure Data

Analysis Population Description

Intention to Treat

Arm/Group Title	Lenalidomide and Azacitidine
Arm/Group Description	azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity. lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.
Measure Participants	37
Number [participants]	26 70.3%

4. Secondary Outcome

Title	Time to Transformation to Acute Myeloid Leukemia or Death
Description	Time (in months) patients took to evolve to myeloid leukemia or death after achieving a complete response using the RECIST criteria
Time Frame	After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months

Outcome Measure Data

Analysis Population Description

Patients who achieved a complete response

Arm/Group Title	Lenalidomide and Azacitidine
Arm/Group Description	azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity. lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.
Measure Participants	16
Median (Full Range) [months]	13.6

5. Secondary Outcome

Title	Time to Relapse After Achieving Complete Response
Time Frame	After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months

Outcome Measure Data

Analysis Population Description

Only patients with a complete response were analysed

Arm/Group Title	Lenalidomide and Azacitidine
Arm/Group Description	azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity. lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.
Measure Participants	16
Median (Full Range) [months]	17

6. Secondary Outcome

Title	Number of Patients That Experience Grade 3 or 4 Treatment Related Non-hematologic Adverse Events
Time Frame	After 7 months

Outcome Measure Data

Analysis Population Description

Intention to Treat

Arm/Group Title	Lenalidomide and Azacitidine
Arm/Group Description	azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity. lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.
Measure Participants	37
Number [participants]	9 24.3%

7. Primary Outcome

Title	PHASE I: Maximum Tolerated Dose of Lenalidomide
Description	Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard "3+3" design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here.
Time Frame	After 1 courses (1 months)

Outcome Measure Data

Analysis Population Description

Participants in Phase I

Arm/Group Title	Lenalidomide and Azacitidine
Arm/Group Description	azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity. lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.
Measure Participants	18
Number [mg orally for 21 days]	10

8. Secondary Outcome

Title	Overall Survival Among Patients With Complete Response
Description	Time (in months) patients who achieved a complete response using the RECIST criteria were alive on study
Time Frame	After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months

Outcome Measure Data

Analysis Population Description

Only patients with complete response

Arm/Group Title	Lenalidomide and Azacitidine
Arm/Group Description	azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity. lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.
Measure Participants	16
Median (Full Range) [months]	37

Adverse Events

Time Frame	28 weeks
Arm/Group Title	Lenalidomide and Azacitidine
Arm/Group Description	azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity. lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.
All Cause Mortality
	Lenalidomide and Azacitidine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lenalidomide and Azacitidine
	Affected / at Risk (%)	# Events
Total	10/37 (27%)
Blood and lymphatic system disorders
Febrile Neutropenia	5/37 (13.5%)	6
Cardiac disorders
Congestive Heart Failure	1/37 (2.7%)	1
Myocardial Infarction	1/37 (2.7%)	1
General disorders
general disorder	1/37 (2.7%)	1
Fatigue (lethargy, malaise, asthenia)	1/37 (2.7%)	1
Constitutional Symptom	1/37 (2.7%)	1
Infections and infestations
Pneumonia	1/37 (2.7%)	1
Infection	1/37 (2.7%)	1
Investigations
Hemoglobin for leukemia studies	1/37 (2.7%)	1
Increased blood urea nitrogen (BUN)	1/37 (2.7%)	1
Neutrophils/granulocytes	2/37 (5.4%)	4
Platelets	2/37 (5.4%)	4
Nervous system disorders
CNS Hemorrhage/bleeding	1/37 (2.7%)	1
weakness/dizziness	1/37 (2.7%)	1
Renal and urinary disorders
Acute kidney injury	1/37 (2.7%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonitis/pulmonary infiltrates	1/37 (2.7%)	1
Skin and subcutaneous tissue disorders
Rash/desquamation	2/37 (5.4%)	2
Vascular disorders
Deep vein or cardiac thrombosis	1/37 (2.7%)	1
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia	1/37 (2.7%)	1
Other (Not Including Serious) Adverse Events
	Lenalidomide and Azacitidine
	Affected / at Risk (%)	# Events
Total	37/37 (100%)
Blood and lymphatic system disorders
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe	11/37 (29.7%)	14
Hemoglobin	16/37 (43.2%)	29
Cardiac disorders
Cardiac Arrhythmia - Other	3/37 (8.1%)	3
Cardiac General - Other	3/37 (8.1%)	4
Gastrointestinal disorders
Heartburn/dyspepsia	4/37 (10.8%)	4
Vomiting	4/37 (10.8%)	5
Gastrointestinal - Other	5/37 (13.5%)	9
Nausea	10/37 (27%)	11
Diarrhea	18/37 (48.6%)	24
Constipation	20/37 (54.1%)	22
General disorders
Rigors/chills	5/37 (13.5%)	5
Edema: limb	5/37 (13.5%)	5
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	6/37 (16.2%)	6
Constitutional Symptoms - Other	8/37 (21.6%)	23
Injection site reaction/extravasation changes	17/37 (45.9%)	20
Pain	19/37 (51.4%)	36
Fatigue (asthenia, lethargy, malaise)	21/37 (56.8%)	24
Infections and infestations
Infection with unknown ANC	3/37 (8.1%)	3
Infection - Other	6/37 (16.2%)	8
Investigations
Weight loss	4/37 (10.8%)	4
Leukocytes (total WBC)	12/37 (32.4%)	34
Neutrophils/granulocytes (ANC/AGC)	17/37 (45.9%)	29
Platelets	18/37 (48.6%)	43
Metabolism and nutrition disorders
Anorexia	7/37 (18.9%)	7
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft Tissue - Other	3/37 (8.1%)	3
Nervous system disorders
Taste alteration (dysgeusia)	4/37 (10.8%)	5
Dizziness	10/37 (27%)	10
Psychiatric disorders
Neurology - Other	5/37 (13.5%)	7
Insomnia	6/37 (16.2%)	6
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory - Other	6/37 (16.2%)	6
Cough	8/37 (21.6%)	8
Dyspnea (shortness of breath)	11/37 (29.7%)	11
Skin and subcutaneous tissue disorders
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)	3/37 (8.1%)	4
Sweating (diaphoresis)	4/37 (10.8%)	4
Dermatology/Skin - Other	11/37 (29.7%)	19
Pruritus/itching	12/37 (32.4%)	17
Rash/desquamation	12/37 (32.4%)	19
Vascular disorders
Hemorrhage/Bleeding - Other	4/37 (10.8%)	7
Hypotension	6/37 (16.2%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.