Treatment of Chronic Lymphocytic Leukemia in Patients Previously Exposed to Rituximab

Study Overview
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Brief Summary
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The purpose of this research is to evaluate the safety and effectiveness of the drugs lenalidomide and ofatumumab in the treatment of chronic lymphocytic leukemia (CLL).

Official Title
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Phase 2 Trial of Intracycle Sequential Ofatumumab and Lenalidomide for the Treatment of Chronic Lymphocytic Leukemia in Patients Previously Exposed to Rituximab

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Ofatumumab
* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have confirmed diagnosis of chronic lymphocytic leukemia (CLL). Prior therapy with at least one regimen containing rituximab Age > 18 years. Life expectancy greater than 12 months. ECOG performance status <2 Patients must have normal organ function as defined in the protocol. Patients must have adequate bone marrow function as defined in the protocol. Ability to understand and the willingness to sign a written informed consent document. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®. Females of childbearing potential (FCBP)† 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 prior to prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued 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. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin. Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 4 weeks or received any monoclonal antibody within 6 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients may not be receiving any other investigational agents or other anti-cancer agents or treatments. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ofatumumab or lenalidomide. Uncontrolled concomitant illness. Pregnant women are excluded from this study because lenalidomide is believed to be teratogenic. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ofatumumab or lenalidomide. Prior treatment with lenalidomide Evidence of laboratory TLS by Cairo-Bishop Definition of Tumor Lysis Syndrome. Subjects may be enrolled upon correction of electrolyte abnormalities. All patients will undergo screening for hepatitis B and may or may not be eligible based on the results as outlined in the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oratumumab and Lenalidomide<br>Single arm, non randomized study Ofatumumab, Lenalidomide: -Ofatumumab 2000 mg (300 mg on first cycle) IV on day 1. Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28. Treatment to be administered for up to 6 cycles | Drug: Ofatumumab<br>* Ofatumumab 2000 mg (300 mg on first cycle) IV on day 1 for up to 6 cycles (28 day cycles) Treatment to be administered for up to 6 cycles<br>* Other names: Arzerra;Drug: Lenalidomide<br>* -Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28 for up to 6 cycles (28 day cycles)<br>* Other names: Revlimid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Obtain early assessment of the efficacy of the intracycle sequential administration of ofatumumab and lenalidomide in the treatment of chronic lymphocytic leukemia (CLL) after prior use of rituximab. Response was categorized according to the IW-CLL criteria which includes the following: Complete remission (CR), CR with incomplete marrow recovery (CRi)Partial remission (PR), Progressive disease (PD), Stable disease (SD). Overall response rate was defined as those who experienced a response of CR, CRi or PR. | 30 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Adverse and Severe Adverse Events | Frequency of adverse and severe adverse events | 30 weeks | 
| Biomarkers Changes During Treatment. | Biomarkers changes during treatment. A minimum of 5 subjects will be enrolled in the biomarkers sub-study. Only those subjects enrolled at MUSC will be considered for the biomarkers sub-study. At day 1 of cycle 1, day 8 of cycle 1, day 1 of cycle 2 and day 8 of cycles 2, blood samples will be obtained for assessment of biomarkers. | 30 Weeks | 
| Frequency of Adverse Events | Number of adverse events occuring in greater than 20% of subjects | 30 weeks | 
| Dose Reductions Due to Adverse Events. | Number of dose reductions due to toxicity. | 30 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed chronic lymphocytic leukemia