Lenalidomide as Initial Treatment of Patients With Chronic Lymphocytic Leukemia (CLL) Age 65 and Older

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00535873
• Collaborator: Celgene (Industry)
• Enrollment: 61
• Location: 1
• Arm: 1
• Duration (Months): 64.1
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

Primary Objective:

• To assess the activity of lenalidomide in patients with previously untreated chronic lymphocytic leukemia (CLL) age 65 and older.

Secondary Objective:

• To assess the tolerability of lenalidomide in patients with untreated CLL age 65 and older

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

Detailed Description

The Study Drug:

Lenalidomide is designed to change the body's immune system and may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may decrease or prevent the growth of cancer cells.

Drug Administration:

If you are found to be eligible to take part in this study, you will take lenalidomide by mouth every morning at about the same time each day for 28 days. Twenty-eight (28) days is considered 1 cycle. The dose and schedule of lenalidomide may be adjusted up or down, depending on how the disease responds and the side effects you may experience. Swallow lenalidomide capsules whole with water at the same time each day. Do not break, chew or open the capsules. If you miss a dose of lenalidomide, take it as soon as you remember on the same day. If you miss taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose).

Concomitant Medications:

Allopurinol will be prescribed for you during the first 14 days of treatment. This medication is taken by mouth and will help protect your kidney function.

Study Visits:

During this study, you will have blood (about 1 tablespoon each) drawn every other week until the best dose of lenalidomide has been found. Blood tests (about 1 tablespoon each) may be done more often if the dose of medication needs to be changed or if you experience intolerable side effects. Women who are able to have children must have a negative urine or blood (less than 1 teaspoon) pregnancy test 10 - 14 days and 24 hours before starting lenalidomide therapy, even if they have not had a menstrual period due to treatment of the disease or had as little as one menstrual period in the past 24 months. If you have regular or no menstrual cycles, you will then have pregnancy tests every week for the first 4 weeks, then every 4 weeks while taking lenalidomide, again when you have been taken off of lenalidomide therapy, and then 28 days after you have stopped taking lenalidomide. If you have irregular menstrual cycles, you will have pregnancy tests every week for the first 4 weeks, then every 2 weeks while taking lenalidomide, again when you have been taken off of lenalidomide therapy, and then 14 days and 28 days after you have stopped taking lenalidomide. Every month for the first 3 months, then at Months 6, 9, 12, and 15 you will have a physical exam to see how you are doing. After the 15-month visit, you will have a physical exam every 6 months.

After the first 3 months, and then every 6 months after that (unless your study doctor does not think it is necessary), you will have a bone marrow biopsy and aspirate performed to check the status of the disease.

Length of Study:

You may stay on this study for as long as you are benefitting. You will be taken off this study early if the disease gets worse or intolerable side effects occur.

This is an investigational study. Lenalidomide is FDA approved and commercially available. Lenalidomide is approved for the treatment of patients with transfusion-dependent anemia due to Low- or Intermediate-1-risk myelodysplastic syndromes associated with the chromosome 5 abnormality with or without other chromosome abnormalities. Lenalidomide is also approved in combination with dexamethasone for the treatment of patients with multiple myeloma that have received at least one prior therapy. Its use in this study, for this disease, is investigational. Up to 60 patients will take part in this study. All will be enrolled at M.

1. Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Lenalidomide as Initial Treatment of Patients With Chronic Lymphocytic Leukemia Age 65 or Older.
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide Lenalidomide starting dose of 5 mg (capsules) by mouth daily for 28 days, one cycle.	Drug: Lenalidomide; Starting dose of 5 mg (capsules) by mouth daily for 28 days, one cycle.; Other Names: Revlimid CC-5013

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [From 3 cycles (90 days) up to 6 cycles (approximately 180 days)]

   ORR defined as number of participants with best response of Complete Response (CR) or Partial Response (PR) out of total number of participants. CR is defined as absence of lymphadenopathy, hepatomegaly or splenomegaly on physical exam. Normal Complete Blood Count (CBC) with polymorphonuclear leukocytes >1500/µL, platelets >100,000/µL, hemoglobin >11.0 g/dL (untransfused); lymphocyte count <5,000/µL; Bone marrow aspirate and biopsy must be normocellular for age with <30% of nucleated cells being lymphocytes. Lymphoid nodules must be absent. PR requires a 50% decrease in peripheral lymphocyte count from , 50% reduction in lymphadenopathy, and/or 50% reduction in splenomegaly/hepatomegaly for a period of at least two months from completion of therapy. These patients must have one of the following: Polymorphonuclear leukocytes 1,500/µL or 50% improvement ; Platelets >100,000/µL or 50% improvement ; Hemoglobin >11.0 g/dL (untransfused) or 50% improvement from pre-treatment value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with untreated CLL or small lymphocytic lymphoma (SLL) with indication to treatment according to NCI Working Group guidelines.Patients that have received single agent rituximab will be allowed to participate in this study.

2. Age 65 or older

3. Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status of 0-2.

4. Adequate renal function indicated by serum creatinine less or equal to 2 and adequate hepatic function indicated as total bilirubin less or equal to upper level of normal and as alanine aminotransferase (ALT) less or equal 2 upper limit of normal (ULN).

5. Able to understand and sign Informed Consent after the investigational nature, study design, risks and benefits have been explained.

6. Able to adhere to the study visit schedule and other protocol requirements.

7. Disease free of prior malignancies for 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. Patients with malignancies with indolent behavior such as prostate cancer treated with radiation can be enrolled in the study as long as they have a reasonable expectation to have been cured with treatment modality received.

8. Females of childbearing potential (FCBP). A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). Must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence

9. Continued from above. from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing.

10. Men must agree to use a condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy.

11. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.

12. All patients must be able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to Acetylsalicylic Acid (ASA) may use warfarin or low molecular weight heparin.

Exclusion Criteria:

1. Known sensitivity to thalidomide or its derivatives.

2. Documented prolymphocytic leukemia (prolymphocytes more than 55% in the blood).

3. Known positivity for HIV or active hepatitis (B or C).

4. A serious medical condition, laboratory abnormality or psychiatric illness that would interfere with the ability of the patient to participate in this program according to the judgement of the Principal Investigator.

5. Active cardiovascular disease as defined by the New York Heart Association Class 3 or

7. History of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.

8. Concurrent use of other chemotherapy agents.

9. Pregnant or breast feeding females. Lactating females must agree not to breast feed while taking lenalidomide.

10. No known history of tuberculosis or recent exposure to tuberculosis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UT MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Celgene

Investigators

• Principal Investigator: Alessandra Ferrajoli, M.D., M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• M.D. Anderson Cancer Center's website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00535873
• Other Study ID Numbers: 2006-0715
• First Posted: Sep 26, 2007
• Last Update Posted: Aug 21, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by M.D. Anderson Cancer Center: Leukemia; CLL; chronic lymphocytic leukemia; SLL; small lymphocytic lymphoma; Untreated CLL; Lenalidomide; CC-5013; Revlimid; Oral
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lenalidomide

Study Results

Participant Flow

Recruitment Details	Recruitment Period: 10/3/2007 through 7/10/2009. All participants recruited at The University of Texas (UT) MD Anderson Cancer Center.
Pre-assignment Detail	Sixty-one participants were registered and signed consent for this study. One participant signed consent but never received study medication.

Arm/Group Title	Lenalidomide
Arm/Group Description	Lenalidomide starting dose of 5 mg (capsules) by mouth daily for 28 days, one cycle.
Period Title: Overall Study
STARTED	60
COMPLETED	60
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Lenalidomide
Arm/Group Description	Lenalidomide starting dose of 5 mg (capsules) by mouth daily for 28 days, one cycle.
Overall Participants	60
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	71
Sex: Female, Male (Count of Participants)
Female	26 43.3%
Male	34 56.7%
Region of Enrollment (participants) [Number]
United States	60 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	ORR defined as number of participants with best response of Complete Response (CR) or Partial Response (PR) out of total number of participants. CR is defined as absence of lymphadenopathy, hepatomegaly or splenomegaly on physical exam. Normal Complete Blood Count (CBC) with polymorphonuclear leukocytes >1500/µL, platelets >100,000/µL, hemoglobin >11.0 g/dL (untransfused); lymphocyte count <5,000/µL; Bone marrow aspirate and biopsy must be normocellular for age with <30% of nucleated cells being lymphocytes. Lymphoid nodules must be absent. PR requires a 50% decrease in peripheral lymphocyte count from , 50% reduction in lymphadenopathy, and/or 50% reduction in splenomegaly/hepatomegaly for a period of at least two months from completion of therapy. These patients must have one of the following: Polymorphonuclear leukocytes 1,500/µL or 50% improvement ; Platelets >100,000/µL or 50% improvement ; Hemoglobin >11.0 g/dL (untransfused) or 50% improvement from pre-treatment value.
Time Frame	From 3 cycles (90 days) up to 6 cycles (approximately 180 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide
Arm/Group Description	Lenalidomide starting dose of 5 mg (capsules) by mouth daily for 28 days, one cycle.
Measure Participants	60
Number [participants]	39 65%

Adverse Events

Time Frame	5 years 4 months
Arm/Group Title	Lenalidomide
Arm/Group Description	Lenalidomide starting dose of 5 mg (capsules) by mouth daily for 28 days, one cycle.
All Cause Mortality
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	24/60 (40%)
Blood and lymphatic system disorders
Abnormal Coagulation tests	1/60 (1.7%)	1
Neutropenia	2/60 (3.3%)	2
Gastrointestinal disorders
Anorexia	1/60 (1.7%)	1
Constipation	1/60 (1.7%)	1
Dehydration	1/60 (1.7%)	1
Necrosis	1/60 (1.7%)	1
General disorders
Fatigue	3/60 (5%)	3
Fever	4/60 (6.7%)	4
Pain	1/60 (1.7%)	1
Infections and infestations
Febrile Neutropenia	1/60 (1.7%)	1
Pneumonia	7/60 (11.7%)	7
Metabolism and nutrition disorders
Hyperbilirubinemia	1/60 (1.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostatic Adenocarcinoma	1/60 (1.7%)	1
Nervous system disorders
Cerebrovascular Ischemia	1/60 (1.7%)	1
Confusion	1/60 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/60 (1.7%)	1
Dyspnea	2/60 (3.3%)	2
Surgical and medical procedures
Hernia Repair	2/60 (3.3%)	2
Hip Replacement Surgery	1/60 (1.7%)	1
Vascular disorders
Embolism	1/60 (1.7%)	1
Vessel injury lower extremity	1/60 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	60/60 (100%)
Blood and lymphatic system disorders
Peripheral Edema	6/60 (10%)	6
Gastrointestinal disorders
Diarrhea	22/60 (36.7%)	22
Constipation	11/60 (18.3%)	11
Nausea	10/60 (16.7%)	10
Anorexia	9/60 (15%)	9
Heartburn	6/60 (10%)	6
General disorders
Fatigue	32/60 (53.3%)	32
Tumor Flare	16/60 (26.7%)	16
GI Pain	7/60 (11.7%)	7
Headache	6/60 (10%)	6
Metabolism and nutrition disorders
Metabolic Laboratory abnormality	9/60 (15%)	9
Hyperglycemia	8/60 (13.3%)	8
Elevated Serum Creatinine	7/60 (11.7%)	7
Hypomagnesemia	7/60 (11.7%)	7
Hyperbilirubinemia	6/60 (10%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	10/60 (16.7%)	10
Nervous system disorders
Sencory Neuropathy	14/60 (23.3%)	14
Neurologic - Other	10/60 (16.7%)	10
Respiratory, thoracic and mediastinal disorders
Dyspnea	6/60 (10%)	6
Skin and subcutaneous tissue disorders
Rash	13/60 (21.7%)	13
Pruritus	8/60 (13.3%)	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.