Lenalidomide in Previously Treated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

• Sponsor: Georg Aue, M.D. (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00439231
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 33
• Location: 1
• Arm: 1
• Duration (Months): 45
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study will evaluate the safety and effectiveness of a new drug called lenalidomide (Revlimid) for treating patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) who relapsed after their initial treatment.

Patients 21 years of age and older with CLL or SLL who have previously received standard treatment may be eligible for this study.

Participants take lenalidomide capsules once a day for 21 days, followed by 21 days off the drug. This constitutes one treatment cycle. Treatment continues for four cycles as long as the medicine is tolerated. After four cycles, patients who respond completely continue treatment for another two cycles; patients who respond partially continue treatment for another four cycles; and patients who do not respond stop treatment but continue to be followed for safety.

...

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma	Drug: Lenalidomide	Phase 2

Detailed Description

There is evidence that lenalidomide has single agent activity in chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL). Optimal dosing of lenalidomide in CLL has not been established yet. A pilot clinical trial in CLL studied single agent lenalidomide cycled every 4 weeks with 25 mg for three weeks on and one week off drug. In this trial dose reductions have been necessary secondary to prolonged neutropenia or thrombocytopenia in a majority of patients. However, there was also remarkable efficacy and evidence for an immune stimulatory effect of lenalidomide. Therefore, we propose this phase II trial using 20 mg lenalidomide (Revlimid(Registered Trademark)) 3 weeks on and 3 weeks off for 4 cycles in subjects who have been previously treated for chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL). Subjects with at least partial response (PR) may go on to receive 4 additional cycles.

The primary objective of the trial is to test the efficacy of a more tolerable dosing scheme of lenalidomide.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Lenalidomide Revlimid(Registered Trademark) in Previously Treated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide (Revlimid) subjects Lenalidomide regimen testing to determine efficacy for CLL/ SLL subjects	Drug: Lenalidomide; Lenalidomide (Revlimid) regimen testing to determine efficacy for SLL/ CLL subjects; Other Names: Revlimid

Outcome Measures

Primary Outcome Measures

1. To Establish the Overall Response Rate Measured at 24 Weeks After First Dose of Lenalidomide Using This Dosing Regimen [24 weeks of lenalidomide therapy]

   To establish the overall response rate based on peripheral blood measures (absolute neutrophil count, platelets, and/or hemoglobin), lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; and bone marrow biopsy measured at 24 weeks after first dose of lenalidomide using this dosing regimen

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

1. Diagnosed with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL).

2. Failed prior standard of care therapy for CLL.

3. Neutrophil count (ANC) greater than or equal to 500/microliter (mcL).

4. Platelet count greater than or equal to 20,000/mcL.

5. Age 21-99.

EXCLUSION CRITERIA:

1. Chronic or current clinically significant infection, including HIV positivity or uncontrolled infection.

2. Eastern Cooperative Oncology Group (ECOG) performance greater than 2.

3. Other concurrent anticancer therapies.

4. Less than 4 weeks from last systemic therapy for CLL. Steroids up to 2 weeks before the start of treatment are permissible.

5. Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient's ability to tolerate protocol therapy.

6. Creatinine greater than 1.5 times the upper limit of normal.

7. Women who are pregnant or nursing, as well as women of childbearing potential who are unwilling to use a dual method of contraception.

8. Men who are unwilling to use a barrier protection.

9. Inability to understand the investigational nature of the study; inability to provide informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• Georg Aue, M.D.
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Georg Aue, MD, NIH National Heart, Lung and Blood Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

None provided.

• Responsible Party: Georg Aue, M.D., NHLBI Hematolgy Clinician, National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT00439231
• Other Study ID Numbers: 070104; 07-H-0104; NCT00465127
• First Posted: Feb 23, 2007
• Last Update Posted: Jan 13, 2014
• Last Verified: Nov 1, 2013

• Keywords provided by Georg Aue, M.D., NHLBI Hematolgy Clinician, National Heart, Lung, and Blood Institute (NHLBI): Monoclonal Antibody Therapy; Biologic Response Modifier Therapy; CLL; SLL; chemo-care (CC) 5013- Revlimid; Chronic Lymphocytic Leukemia; Small Lymphocytic Leukemia
• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lenalidomide

Study Results

Participant Flow

Arm/Group Title	CLL Subjects Response to Lenalidomide (Revlimid)
Arm/Group Description	To establish a response rate to lenalidomide (Revlimid) in subjects with CLL/SLL using a 3 week on, 3 week off dosing regimen. The responses will be categorized using the revised 1996 National Cancer Institute - sponsored working guidelines. The response rate will be based on changes in peripheral blood measures (ANC, platelets and/or hemoglobin), lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; and bone marrow biopsy measured at 24 weeks after the first dose of lenalidomide using the protocol dosing regimen. Complete responders will respond to treatment after 2 cycles. Partial responders will respond to treatment after 4 cycles.
Period Title: Overall Study
STARTED	33
COMPLETED	5
NOT COMPLETED	28

Baseline Characteristics

Arm/Group Title	CLL Subjects Response to Lenalidomide (Revlimid)
Arm/Group Description	To establish a response rate to lenalidomide (Revlimid) in subjects with chronic lymphocytic leukemia (CLL)/ small lymphocytic leukemia (SLL) using a 3 week on, 3 week off dosing regimen. The responses will be categorized using the revised 1996 National Cancer Institute - sponsored working guidelines. The response rate will be based on changes in peripheral blood measures (ANC, platelets and/or hemoglobin), lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; and bone marrow biopsy measured at 24 weeks after the first dose of lenalidomide using the protocol dosing regimen. Complete responders will respond to treatment after 2 cycles. Partial responders will respond to treatment after 4 cycles.
Overall Participants	33
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	19 57.6%
>=65 years	14 42.4%
Sex: Female, Male (Count of Participants)
Female	7 21.2%
Male	26 78.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	29 87.9%
Unknown or Not Reported	4 12.1%
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	4 12.1%
White	26 78.8%
More than one race	0 0%
Unknown or Not Reported	3 9.1%

Outcome Measures

1. Primary Outcome

Title	To Establish the Overall Response Rate Measured at 24 Weeks After First Dose of Lenalidomide Using This Dosing Regimen
Description	To establish the overall response rate based on peripheral blood measures (absolute neutrophil count, platelets, and/or hemoglobin), lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; and bone marrow biopsy measured at 24 weeks after first dose of lenalidomide using this dosing regimen
Time Frame	24 weeks of lenalidomide therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CLL Subject Response Rate After Lenalidomide Therapy
Arm/Group Description	To establish a response rate to lenalidomide (Revlimid) in subjects with chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) using a 3 week on, 3 week off dosing regimen. Complete responders will respond to treatment after 2 cycles. Partial responders will respond to treatment after 4 cycles.
Measure Participants	33
Complete response	0 0%
Partial response	5 15.2%
No response	28 84.8%

Adverse Events

Arm/Group Title	CLL Subjects Treated With Lenalidomide (Revlimid)
Arm/Group Description
All Cause Mortality
	CLL Subjects Treated With Lenalidomide (Revlimid)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	CLL Subjects Treated With Lenalidomide (Revlimid)
	Affected / at Risk (%)	# Events
Total	8/33 (24.2%)
Blood and lymphatic system disorders
DVT	1/33 (3%)
Tumor flare syndrome	7/33 (21.2%)
Other (Not Including Serious) Adverse Events
	CLL Subjects Treated With Lenalidomide (Revlimid)
	Affected / at Risk (%)	# Events
Total	32/33 (97%)
Blood and lymphatic system disorders
ankle edema	1/33 (3%)
bruising inner arm	1/33 (3%)
decrease in hemoglobin	8/33 (24.2%)
decrease in neutrophils	19/33 (57.6%)
decrease in platelets	19/33 (57.6%)
DVT leg	1/33 (3%)
elbow bruising	1/33 (3%)
flu like symptoms	3/33 (9.1%)
hematoma	2/33 (6.1%)
hypophosphatemia	1/33 (3%)
increase ALT	1/33 (3%)
lymph node swelling	3/33 (9.1%)
lymphedema	1/33 (3%)
swollen lymph node	1/33 (3%)
Tumor flare syndrome	13/33 (39.4%)
Cardiac disorders
hypotension	2/33 (6.1%)
Ear and labyrinth disorders
decreased hearing	1/33 (3%)
ear pressure	1/33 (3%)
middle ear pain	1/33 (3%)
Eye disorders
blurred vision	1/33 (3%)
dry eye	1/33 (3%)
edema ocular	1/33 (3%)
uvietus	1/33 (3%)
Gastrointestinal disorders
abdominal bloating	3/33 (9.1%)
abdominal cramps	3/33 (9.1%)
abdominal distention	2/33 (6.1%)
abdominal pain	8/33 (24.2%)
change in taste	3/33 (9.1%)
constipation	8/33 (24.2%)
decrease in creatinine	1/33 (3%)
diarrhea	9/33 (27.3%)
dry mouth	1/33 (3%)
heartburn	1/33 (3%)
increase ALT	2/33 (6.1%)
increase AST	2/33 (6.1%)
nausea	5/33 (15.2%)
organomegaly	1/33 (3%)
stomach pain	1/33 (3%)
urinary tract infection	1/33 (3%)
vomiting	3/33 (9.1%)
General disorders
ankle swelling	1/33 (3%)
chills	4/33 (12.1%)
cold sore	1/33 (3%)
cough	1/33 (3%)
fatigue	19/33 (57.6%)
fever	5/33 (15.2%)
insomnia	1/33 (3%)
lower extremity edema	1/33 (3%)
mouth lesion	1/33 (3%)
mouth/lip sore	1/33 (3%)
pedal edema	1/33 (3%)
sweating	6/33 (18.2%)
weight loss	9/33 (27.3%)
Infections and infestations
CMV infection	1/33 (3%)
Gastrointestinal infection	1/33 (3%)
gum infection	1/33 (3%)
oral cavity infeciton	1/33 (3%)
oral ulcers	1/33 (3%)
shingles	1/33 (3%)
tooth abscess	1/33 (3%)
upper respiratory infection	1/33 (3%)
Musculoskeletal and connective tissue disorders
arm pain	2/33 (6.1%)
back pain	5/33 (15.2%)
bruising arms & back	1/33 (3%)
chest pain	1/33 (3%)
elbow pain	2/33 (6.1%)
feet pain	1/33 (3%)
foot cramps	1/33 (3%)
foot/ankle pain	1/33 (3%)
general body aches	1/33 (3%)
generalize bruising	1/33 (3%)
hand cramps	1/33 (3%)
joint pain	1/33 (3%)
leg cramp	1/33 (3%)
leg cramps	1/33 (3%)
leg pain	2/33 (6.1%)
lower extremity cramps	1/33 (3%)
lower extremity leg cramps	1/33 (3%)
lower extremity pain	3/33 (9.1%)
lower extremity rash	1/33 (3%)
muscle cramp	1/33 (3%)
muscle cramps	1/33 (3%)
Musculoskeletal pain	2/33 (6.1%)
neck pain	2/33 (6.1%)
ocular infection	1/33 (3%)
petechiae legs	1/33 (3%)
pleuritic back pain	1/33 (3%)
scalp rash	1/33 (3%)
shoulder pain	3/33 (9.1%)
skin rash	1/33 (3%)
Nervous system disorders
agitation	1/33 (3%)
hallucinations	1/33 (3%)
head/ arm nueropathy	1/33 (3%)
headache	6/33 (18.2%)
insomnia	2/33 (6.1%)
syncope	12/33 (36.4%)
Psychiatric disorders
depressed	1/33 (3%)
Reproductive system and breast disorders
upper respiratory infection	1/33 (3%)
Respiratory, thoracic and mediastinal disorders
bronchitis	1/33 (3%)
cough	3/33 (9.1%)
dyspnea	10/33 (30.3%)
mouth lesion	1/33 (3%)
pulmonary infiltrate	1/33 (3%)
rales	1/33 (3%)
sinus infection	1/33 (3%)
sore throat	2/33 (6.1%)
throat pain	1/33 (3%)
upper respiratory infection	16/33 (48.5%)
Skin and subcutaneous tissue disorders
facial rash	1/33 (3%)
hand rash	1/33 (3%)
head rash	1/33 (3%)
knee rash	1/33 (3%)
pruritis	5/33 (15.2%)
rash axilla	1/33 (3%)
rash chest	1/33 (3%)
rash leg	1/33 (3%)
rash scalp	2/33 (6.1%)
rash torso	1/33 (3%)
rash waistband	1/33 (3%)
scalp rash	2/33 (6.1%)
skin rash	14/33 (42.4%)
skin rash lip	1/33 (3%)

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.