Lenalidomide (Revlimid®, CC-5013) in Subjects With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

• ClinicalTrials.gov Identifier: NCT00179673
• Recruitment Status: Completed
• First Posted: September 16, 2005
• Results First Posted: October 14, 2013
• Last Update Posted: November 28, 2013
• Sponsor: Celgene Corporation
• Collaborator: Prologue Research International
• Information provided by (Responsible Party): Celgene ( Celgene Corporation )

• Study Type: Interventional
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Hodgkins Lymphoma
• Intervention: Drug: Lenalidomide
• Enrollment: 43

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Period Title: Overall Study
Started	43
Received Study Drug	43
Completed	0 [1]
Not Completed	43
Reason Not Completed
Adverse Event	7
Lack of Efficacy	15
Withdrawal by Subject	3
Death	4
Other Observations and options	14
[1] Completed refers to participants ongoing in the study at the time of analysis.

Baseline Characteristics

Arm/Group Title		Lenalidomide
Arm/Group Description		Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Overall Number of Baseline Participants		43
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	43 participants
		64.6 (10.95)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	43 participants
<65 years		24
65 - 75		10
>75 years		9
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	43 participants
	Female	17 39.5%
	Male	26 60.5%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	43 participants
White		37
Black		4
Hispanic		0
Asian/Pacific Islander		1
American Indian/Alaska Native		0
Other = Unspecified		1
NHL Duration; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	43 participants
		5.6 (4.38)
Non-Hodgkin's Lymphoma (NHL) Histology [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	43 participants
Follicular lymphoma grade 1 or 2		22
Small Lymphocytic lymphoma		18
Nodal marginal-zone B-cell lymphoma		2
Extranodal marginal-zone B-cell type (MALT)		1
		[1] Measure Description: I: The lymphoma is in only 1 lymph node area or 1 area of a single organ outside the lymph system. II: The lymphoma is in 2 or more groups of lymph nodes on the same side of the diaphragm, or extends from a single group of node(s) into a nearby organ. III: The lymphoma is found in lymph node areas on both sides of the diaphragm, or may also have spread into an area or organ next to the lymph nodes, the spleen, or both. IV: The lymphoma has spread outside the lymph system into an organ that is not next to an involved node or has spread to bone marrow, liver, brain, spinal cord or the pleura.
Non-Hodgkin's Lymphoma (NHL)-Stage [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	43 participants
Stage I		1
Stage II		11
Stage III		6
Stage IV		25
		[1] Measure Description: I: The lymphoma is in only 1 lymph node area or 1 area of a single organ outside the lymph system. II: The lymphoma is in 2 or more groups of lymph nodes on the same side of the diaphragm, or extends from a single group of node(s) into a nearby organ. III: The lymphoma is found in lymph node areas on both sides of the diaphragm, or may also have spread into an area or organ next to the lymph nodes, the spleen, or both. IV: The lymphoma has spread outside the lymph system into an organ that is not next to an involved node or has spread to bone marrow, liver, brain, spinal cord or the pleura.
International Prognostic Index (IPI)] [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	43 participants
Low (0 to 1)		14
Low/Intermediate (2)		15
High/Intermediate (3)		6
High (4 to 5)		8
		[1] Measure Description: A clinical tool to aid in predicting the prognosis of patients with NHL. One point is assigned for each of the following risk factors: Age greater than 60 years; Stage III or IV disease; Elevated serum lactate dehydrogenase; ECOG performance status of 2, 3, or 4; 1 extranodal site The sum of the points allotted correlates with the following risk groups: Low risk (0-1 points): 5-year survival of 73%; Low-intermediate risk (2 points): 5-year survival of 51%; High-intermediate risk (3 points): 5-year survival of 43%; High risk (4-5 points): 5-year survival of 26%.
Eastern Cooperative Oncology Group (ECOG) performance status [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	43 participants
0 = fully active, no restrictions;		27
1 = restricted but ambulatory and capable of light		12
2 = ambulatory and capable of self care but unable		4
		[1] Measure Description: ECOG-Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determines appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Response
Description	Response was defined as participants with a complete response (CR), unconfirmed complete response (Cru) or partial response (PR), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. CR: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities. Cru: Criteria for CR above but with 1 or more of the following: A residual lymph node mass > 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the products of diameters (SPD); Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia). PR: ≥ 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD.
Time Frame	From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population, which included all enrolled patients who received at least 1 dose of study drug. Patients who dropped out without having a response assessment or who had a response after they had received other anti-cancer treatments were considered non-responders.

Arm/Group Title	Lenalidomide
Arm/Group Description:	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Overall Number of Participants Analyzed	43
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	23.3; (11.8 to 38.6)

2. Secondary Outcome

Title	Percentage of Participants With Tumor Control
Description	Tumor control was defined as participants with a complete response, unconfirmed complete response, partial response or stable disease (SD), assessed using the International Workshop Lymphoma Response Criteria (IWLRC) and based on best responses as determined by the investigator. SD was defined as a response less than a PR (see above) but not Progressive Disease (PD). PD was defined as; ≥ 50 % increase from nadir in the SPD of any previously identified abnormal node for partial responders or non-responders.; Appearance of any new lesion during or at the end of therapy.
Time Frame	From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population. Patients who dropped out without having a response assessment or who had a response after they had received other anti-cancer treatments were considered non-responders

Arm/Group Title	Lenalidomide
Arm/Group Description:	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Overall Number of Participants Analyzed	43
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	60.5; (44.4 to 75.0)

3. Secondary Outcome

Title	The Duration of Response
Description	The duration of response was calculated as the first response assessment demonstrating evidence of at least a partial response to the first documentation of progressive disease (as determined by computed tomography scan) or death due to NHL, whichever occurred first. For participants without documentation of progression, the duration of response was censored at the last date of tumor assessment indicating no progression. Median was based on the Kaplan-Meier estimate.
Time Frame	From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months

Outcome Measure Data

Analysis Population Description

Includes participants with a response to treatment

Arm/Group Title	Lenalidomide
Arm/Group Description:	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Overall Number of Participants Analyzed	10
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (15.5 to NA)

[1]

The median was not reached due to the low number of events.

4. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Progression-free survival was defined as the time from the start of study drug therapy to the first observation of disease progression or death due to any cause, whichever came first. Participants who withdrew for any reason or received another NHL therapy including stem cell transplantation without documented progressive disease were censored on the date of their last adequate response assessment indicating no progression (or last adequate assessment prior to receiving other NHL therapy). Participants who were still active without progressive disease at the time of the data cut-off date were censored on the date of their last adequate response assessment.
Time Frame	From enrollment through study completion. Median duration on study was 4.4 months with a maximum of 32 months

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Lenalidomide
Arm/Group Description:	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Overall Number of Participants Analyzed	43
Median (95% Confidence Interval); Unit of Measure: months
	4.4; (2.5 to 10.4)

5. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	The Investigator determined the relationship between the administration of study drug and the occurrence of an AE as suspected if the temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other drugs, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event. The Investigator graded the severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria and the following scale: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death A Serious AE is defined as any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or constitutes an important medical event.
Time Frame	From the start of study drug through 30 days after the last dose of study drug. Maximum time on study drug was 13.8 months.

Outcome Measure Data

Analysis Population Description

Safety Population, which includes all participants who received at least one dose of study drug.

Arm/Group Title	Lenalidomide
Arm/Group Description:	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
Overall Number of Participants Analyzed	43
Measure Type: Number; Unit of Measure: participants
At least one Adverse Event (AE)	42
≥ 1 AE related to study drug	37
Grade (GR) 3-5 AE	27
Grade 3-5 AE related to study drug	24
Serious adverse event (SAE)	18
SAE related to study drug	10
AE leading to discontinuation of study drug	9
Related AE leading to study drug discontinuation	5
AE leading to dose reduction or interruption	27

Adverse Events

Time Frame	From the start of study drug through 30 days after the last dose of study drug. Maximum time on study drug was 13.8 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Lenalidomide
Arm/Group Description	Participants received single-agent lenalidomide 25 mg orally once daily on Days 1 to 21 of every 28-day cycle for up to 52 weeks or until disease progression developed, lenalidomide treatment was discontinued for any reason, or the study was terminated.
All-Cause Mortality
	Lenalidomide
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Lenalidomide
	Affected / at Risk (%)
Total	10/43 (23.26%)
Blood and lymphatic system disorders
Anemia Not Otherwise Specified (NOS) † 1	1/43 (2.33%)
Lymph Node Pain † 1	1/43 (2.33%)
Febrile Neutropenia † 1	1/43 (2.33%)
Pancytopenia † 1	1/43 (2.33%)
Thrombocytopenia † 1	1/43 (2.33%)
Gastrointestinal disorders
Abdominal Pain NOS † 1	2/43 (4.65%)
Constipation † 1	1/43 (2.33%)
Diarrhoea NOS † 2	1/43 (2.33%)
General disorders
Pyrexia † 1	1/43 (2.33%)
Infections and infestations
Sepsis NOS † 1	1/43 (2.33%)
Nervous system disorders
Transient Ischaemic Attack † 1	1/43 (2.33%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism † 1	1/43 (2.33%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA; 2 Term from vocabulary, MedDRA V 5.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Lenalidomide
	Affected / at Risk (%)
Total	41/43 (95.35%)
Blood and lymphatic system disorders
Neutropenia † 1	19/43 (44.19%)
Thrombocytopenia † 1	15/43 (34.88%)
Leukopenia NOS † 1	10/43 (23.26%)
Anaemia NOS † 1	7/43 (16.28%)
Gastrointestinal disorders
Constipation † 1	13/43 (30.23%)
Diarrhoea NOS † 1	13/43 (30.23%)
Nausea † 1	8/43 (18.60%)
Abdominal Pain NOS † 1	5/43 (11.63%)
General disorders
Fatigue † 1	20/43 (46.51%)
Oedema Peripheral † 1	4/43 (9.30%)
Pain NOS † 1	4/43 (9.30%)
Pyrexia † 1	4/43 (9.30%)
Investigations
Haemoglobin Decreased † 1	8/43 (18.60%)
Neutrophil Count Decreased † 1	8/43 (18.60%)
Alanine Aminotransferase Increased † 1	5/43 (11.63%)
Blood Alkaline Phosphatase NOS Increased † 1	4/43 (9.30%)
White Blood Cell Count Decreased † 1	4/43 (9.30%)
Aspartate Aminotransferase Increased † 1	3/43 (6.98%)
Platelet Count Decreased † 1	3/43 (6.98%)
Metabolism and nutrition disorders
Hyperglycaemia NOS † 1	5/43 (11.63%)
Hyperkalemia † 1	3/43 (6.98%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	7/43 (16.28%)
Muscle Cramp † 1	5/43 (11.63%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour Flare † 1	4/43 (9.30%)
Nervous system disorders
Headache † 1	4/43 (9.30%)
Hypoaesthesia † 1	3/43 (6.98%)
Psychiatric disorders
Insomnia † 1	6/43 (13.95%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	7/43 (16.28%)
Pharyngitis † 1	5/43 (11.63%)
Skin and subcutaneous tissue disorders
Rash NOS † 1	10/43 (23.26%)
Pruritus † 1	5/43 (11.63%)
Night Sweats † 1	3/43 (6.98%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (5.1)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS 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.

The investigator shall have the right to publish and/or present study data provided that the investigator shall (i) furnish the sponsor a copy of any proposed publication or presentation generally thirty (60) days in advance of the submission, (ii) delete any confidential information of the sponsor, and (iii) delay submission for generally up to ninety (90) days to permit the preparation and filing of intellectual property applications or until sponsor gives its consent in a timely manner.

Results Point of Contact

• Name/Title: Senior Manager, Clinical Trials Disclosure
• Organization: Celgene Corporation
• Phone: 888-260-1599
• EMail: clinicaltrialdisclosure@celgene.com

Publications of Results:

Witzig TE, Wiernik PH, Moore T, Reeder C, Cole C, Justice G, Kaplan H, Voralia M, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Vose JM. Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin's Lymphoma. J Clin Oncol. 2009 Nov 10;27(32):5404-9. doi: 10.1200/JCO.2008.21.1169. Epub 2009 Oct 5.

• Responsible Party: Celgene ( Celgene Corporation )
• ClinicalTrials.gov Identifier: NCT00179673 History of Changes
• Other Study ID Numbers: CC-5013-NHL-001
• First Submitted: September 10, 2005
• First Posted: September 16, 2005
• Results First Submitted: August 9, 2013
• Results First Posted: October 14, 2013
• Last Update Posted: November 28, 2013