Lenalidomide as Chemoprevention in Treating Patients With High-Risk, Early-Stage B-Cell Chronic Lymphocytic Leukemia

• Sponsor: Roswell Park Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01649791
• Collaborator: National Cancer Institute (NCI) (NIH), Celgene Corporation (Industry)
• Enrollment: 8
• Location: 1
• Arm: 1
• Duration (Months): 57
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This clinical trial studies lenalidomide as chemoprevention in treating patients with high-risk, early stage B-cell chronic lymphocytic leukemia (B-CLL). Chemoprevention is the use of certain drugs to keep cancer from forming. The use of lenalidomide may slow disease progression in patients with early stage B-cell chronic lymphocytic leukemia

Condition or Disease	Intervention/Treatment	Phase
B-cell Chronic Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia	Drug: lenalidomide; Other: laboratory biomarker analysis; Procedure: lymph node biopsy; Procedure: bone marrow aspiration; Other: pharmacological study; Other: flow cytometry	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. To determine time to progression in patients with high risk CLL.

SECONDARY OBJECTIVES:

1. Overall response rate including (complete remission [CR]+partial remission [PR]) of lenalidomide.

2. To determine the incidence of immune mediated flare reaction. III. To characterize the toxicity profile of single agent lenalidomide in previously untreated B-CLL.

3. To correlate expression of B-CLL co-stimulatory ligands and clinical efficacy of lenalidomide in this patient population.

4. To conduct correlative studies.

OUTLINE: Patients receive lenalidomide orally (PO) once daily for 4 weeks. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Lenalidomide as a Chemopreventive Agent for Patients With High-Risk, Early Stage B-Chronic Lymphocytic Leukemia (CLL)
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (lenalidomide as chemoprevention) Patients receive lenalidomide PO once daily for 4 weeks. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Drug: lenalidomide; Given orally; Other Names: CC-5013 IMiD-1 Revlimid ; Other: laboratory biomarker analysis; Correlative study; Procedure: lymph node biopsy; Correlative study; Other Names: Biopsy of Lymph Node ; Procedure: bone marrow aspiration; Correlative study; Other: pharmacological study; Correlative study; Other Names: pharmacological studies ; Other: flow cytometry; Correlative study

Outcome Measures

Primary Outcome Measures

1. Median Progression-free Survival [24 months]

Secondary Outcome Measures

1. Overall Response Rate (CR+PR) [24 months]

2. Incidence of Immune Mediated Flare Reaction [24 months]

   Number of participants with Tumour flare.

3. Expression of B-CLL Co-stimulatory Ligands, Mic-A, and Mic-B Assessed by Flow Cytometry [8 days]

   PI left the institute and the data was not collected.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Patients must have a definitive diagnosis of B-CLL as defined by the International Workshop on CLL (IWCll) criteria Patient must have early stage B-CLL defined as Rai stage 0, 1 or 2 Patients must not have received any prior treatment for management of B-CLL

Patients must be assessed to have high risk B-CLL as defined by either one of the following criterion:

• High-risk cytogenetics (either 17p deletion or 11q deletion);

• Unmutated immunoglobulin heavy chain gene rearrangement Patents must understand and voluntarily sign an informed consent form Able to adhere to the study visit schedule and other protocol requirements Patients must have measurable disease either an absolute lymphocyte counts (ALC) of more than 5,000/ul or measurable lymphadenopathy or organomegaly Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL 10-14 days prior to and again within 24 hours before starting lenalidomide and must either commit to continue abstinence 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 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure Able to take aspirin (81 or 325mg) or warfarin sodium daily as prophylactic anticoagulation Absolute neutrophil count >= 1.0 x 10^{9/L Platelet count >= 30 x 10}9/L Serum creatinine =< 1.5 x upper limit of normal (ULN) Total bilirubin =< 1.5 mg/dL Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) < 2 x ULN or =< 5 x ULN if hepatic metastases are present

Exclusion Criteria:

Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form Pregnant or lactating females (lactating females must agree not to breast feed while taking lenalidomide) Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study Use of any other experimental drug or therapy within 28 days of baseline Known hypersensitivity to thalidomide or lenalidomide Prior history of development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs Patients who have been treated with any prior therapy for B-CLL Patients with history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix, unless in complete remission and off therapy for that disease for > 3 years) Patient with history of cardiac arrest within the past 6 months Any prior use of lenalidomide Concurrent use of other anti-cancer agents or treatments Known history of hepatitis B or C Known human immunodeficiency virus (HIV) positive status

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263

Sponsors and Collaborators

• Roswell Park Cancer Institute
• National Cancer Institute (NCI)
• Celgene Corporation

Investigators

• Principal Investigator: Myron Czuczman, Roswell Park Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT01649791
• Other Study ID Numbers: I 136908; NCI-2009-01327; NCT01003821
• First Posted: Jul 25, 2012
• Last Update Posted: Jun 30, 2016
• Last Verified: May 1, 2016

• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lenalidomide

Study Results

Participant Flow

Arm/Group Title	Treatment (Lenalidomide as Chemoprevention)
Arm/Group Description	Patients receive lenalidomide PO once daily for 4 weeks. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. lenalidomide: Given orally laboratory biomarker analysis: Correlative study lymph node biopsy: Correlative study bone marrow aspiration: Correlative study pharmacological study: Correlative study flow cytometry: Correlative study
Period Title: Overall Study
STARTED	8
COMPLETED	5
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Treatment (Lenalidomide as Chemoprevention)
Arm/Group Description	Patients receive lenalidomide PO once daily for 4 weeks. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. lenalidomide: Given orally laboratory biomarker analysis: Correlative study lymph node biopsy: Correlative study bone marrow aspiration: Correlative study pharmacological study: Correlative study flow cytometry: Correlative study
Overall Participants	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63 (8.8)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 37.5%
>=65 years	5 62.5%
Sex: Female, Male (Count of Participants)
Female	1 12.5%
Male	7 87.5%

Outcome Measures

1. Primary Outcome

Title	Median Progression-free Survival
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

All treated and eligible patients.

Arm/Group Title	Treatment (Lenalidomide as Chemoprevention)
Arm/Group Description	Patients receive lenalidomide PO once daily for 4 weeks. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. lenalidomide: Given orally laboratory biomarker analysis: Correlative study lymph node biopsy: Correlative study bone marrow aspiration: Correlative study pharmacological study: Correlative study flow cytometry: Correlative study
Measure Participants	8
Median (95% Confidence Interval) [months]	43.7

2. Secondary Outcome

Title	Overall Response Rate (CR+PR)
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

All treated and eligible patients.

Arm/Group Title	Treatment (Lenalidomide as Chemoprevention)
Arm/Group Description	Patients receive lenalidomide PO once daily for 4 weeks. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. lenalidomide: Given orally laboratory biomarker analysis: Correlative study lymph node biopsy: Correlative study bone marrow aspiration: Correlative study pharmacological study: Correlative study flow cytometry: Correlative study
Measure Participants	8
Number [percentage of participants]	100 1250%

3. Secondary Outcome

Title	Incidence of Immune Mediated Flare Reaction
Description	Number of participants with Tumour flare.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

All treated and eligible patients.

Arm/Group Title	Treatment (Lenalidomide as Chemoprevention)
Arm/Group Description	Patients receive lenalidomide PO once daily for 4 weeks. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. lenalidomide: Given orally laboratory biomarker analysis: Correlative study lymph node biopsy: Correlative study bone marrow aspiration: Correlative study pharmacological study: Correlative study flow cytometry: Correlative study
Measure Participants	8
Number [participants]	4 50%

4. Secondary Outcome

Title	Expression of B-CLL Co-stimulatory Ligands, Mic-A, and Mic-B Assessed by Flow Cytometry
Description	PI left the institute and the data was not collected.
Time Frame	8 days

Outcome Measure Data

Analysis Population Description

No participants were analyzed.

Arm/Group Title	Treatment (Lenalidomide as Chemoprevention)
Arm/Group Description	Patients receive lenalidomide PO once daily for 4 weeks. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. lenalidomide: Given orally laboratory biomarker analysis: Correlative study lymph node biopsy: Correlative study bone marrow aspiration: Correlative study pharmacological study: Correlative study flow cytometry: Correlative study
Measure Participants	0

Adverse Events

Arm/Group Title	Treatment (Lenalidomide as Chemoprevention)
Arm/Group Description	Patients receive lenalidomide PO once daily for 4 weeks. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. lenalidomide: Given orally laboratory biomarker analysis: Correlative study lymph node biopsy: Correlative study bone marrow aspiration: Correlative study pharmacological study: Correlative study flow cytometry: Correlative study
All Cause Mortality
	Treatment (Lenalidomide as Chemoprevention)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Lenalidomide as Chemoprevention)
	Affected / at Risk (%)	# Events
Total	2/8 (25%)
Musculoskeletal and connective tissue disorders
Muscular weakness	1/8 (12.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Lenalidomide as Chemoprevention)
	Affected / at Risk (%)	# Events
Total	8/8 (100%)
Blood and lymphatic system disorders
Anaemia	1/8 (12.5%)	4
Lymphadenopathy	1/8 (12.5%)	1
Neutropenia	5/8 (62.5%)	19
Thrombocytopenia	1/8 (12.5%)	1
Gastrointestinal disorders
Abdominal distension	1/8 (12.5%)	1
Abdominal pain	1/8 (12.5%)	2
Constipation	2/8 (25%)	2
Diarrhoea	7/8 (87.5%)	9
Dry mouth	1/8 (12.5%)	1
Dyspepsia	1/8 (12.5%)	1
Faeces hard	1/8 (12.5%)	1
Flatulence	1/8 (12.5%)	1
Gastrooesophageal reflux disease	1/8 (12.5%)	1
Nausea	1/8 (12.5%)	4
Vomiting	1/8 (12.5%)	1
General disorders
Chills	1/8 (12.5%)	1
Fatigue	7/8 (87.5%)	8
Injection site pain	1/8 (12.5%)	1
Oedema	2/8 (25%)	2
Oedema peripheral	2/8 (25%)	2
Pain	1/8 (12.5%)	2
Pyrexia	1/8 (12.5%)	4
Immune system disorders
Hypersensitivity	1/8 (12.5%)	1
Infections and infestations
Cellulitis	1/8 (12.5%)	3
Ear infection	1/8 (12.5%)	1
Infection	2/8 (25%)	2
Pharyngitis	1/8 (12.5%)	1
Pneumonia	1/8 (12.5%)	2
Sinusitis	3/8 (37.5%)	3
Upper respiratory tract infection	5/8 (62.5%)	5
Vulvovaginal mycotic infection	1/8 (12.5%)	1
Injury, poisoning and procedural complications
Skin laceration	1/8 (12.5%)	1
Investigations
Alanine aminotransferase increased	1/8 (12.5%)	1
Aspartate aminotransferase increased	1/8 (12.5%)	1
Blood phosphorus increased	2/8 (25%)	2
Blood potassium decreased	1/8 (12.5%)	1
Blood potassium increased	1/8 (12.5%)	1
Weight decreased	3/8 (37.5%)	6
Metabolism and nutrition disorders
Anorexia	1/8 (12.5%)	1
Hyperkalaemia	1/8 (12.5%)	4
Hyperphosphataemia	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/8 (25%)	3
Back pain	1/8 (12.5%)	2
Bursitis	1/8 (12.5%)	1
Muscle spasms	4/8 (50%)	5
Muscular weakness	1/8 (12.5%)	2
Myalgia	2/8 (25%)	2
Pain in extremity	1/8 (12.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour flare	4/8 (50%)	8
Nervous system disorders
Dizziness	1/8 (12.5%)	1
Headache	1/8 (12.5%)	1
Hypoaesthesia	2/8 (25%)	3
Hypogeusia	3/8 (37.5%)	4
Lethargy	1/8 (12.5%)	1
Paraesthesia	1/8 (12.5%)	1
Tremor	1/8 (12.5%)	2
Psychiatric disorders
Insomnia	1/8 (12.5%)	1
Libido decreased	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	3/8 (37.5%)	3
Dysphonia	1/8 (12.5%)	1
Dyspnoea	4/8 (50%)	4
Nasal congestion	1/8 (12.5%)	1
Pharyngolaryngeal pain	2/8 (25%)	4
Rhinorrhoea	4/8 (50%)	4
Sinus congestion	1/8 (12.5%)	1
Throat irritation	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/8 (12.5%)	2
Night sweats	2/8 (25%)	4
Pruritus	2/8 (25%)	2
Rash	5/8 (62.5%)	11
Rash erythematous	1/8 (12.5%)	1
Rash papular	1/8 (12.5%)	1
Rash pruritic	1/8 (12.5%)	1
Surgical and medical procedures
Tooth extraction	1/8 (12.5%)	1
Vascular disorders
Hot flush	1/8 (12.5%)	1

Limitations/Caveats

This trial did not reach full accrual.

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.