Lenalidomide and Obinutuzumab in Treating Patients With Recurrent or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Study Overview
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Brief Summary
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This phase II trial studies how well lenalidomide and obinutuzumab work in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as obinutuzumab, may interfere with the ability of cancer cells to grow and spread. Giving lenalidomide and obinutuzumab may work better in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

Detailed Description
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PRIMARY OBJECTIVES: I. Overall response defined as achievement of complete response (CR) or partial response (PR). SECONDARY OBJECTIVES: I. Safety of the combination. II. Response according to prognostic markers at diagnosis. III. Time to next treatment. IV. Overall survival. OUTLINE: Patients receive obinutuzumab intravenously (IV) over 3-4 hours on days 1, 2, 8, and 15 of course 1 and day 1 of courses 2-6 and lenalidomide orally (PO) once daily (QD) on days 9-28 of course 1 and days 1-28 of all subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may continue to receive lenalidomide PO QD in the absence of disease progression or unacceptable toxicity.

Official Title
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Combination of Lenalidomide and Obinutuzumab (GA101) in Patients With Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Conditions
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Recurrent Chronic Lymphocytic Leukemia, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Small Lymphocytic Lymphoma

Intervention / Treatment
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* Drug: Lenalidomide
* Biological: Obinutuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand and to provide voluntarily informed consent Have documented chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) according to National Cancer Institute (NCI) criteria Recurrent or refractory disease according to NCI criteria Patient are eligible if they have received one or more prior treatment Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Life expectancy > 6 months Serum creatinine less or equal to 2 mg/dl Total bilirubin less or equal to 2 mg/dl Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) less or equal to two times the upper normal limit Disease free of prior malignancies for 3 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 or surgery can be enrolled in the study as long as they have a reasonable expectation to have been cured with the treatment modality received No prior history of myelodysplastic syndrome or other myeloid malignancy All participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS) program, and be willing and able to comply with the requirements of the Revlimid REMS Females of childbearing potential (FCBP) must have a negative serum and/or urine pregnancy test with a sensitive of at least 50 mIU/mL within 10-14 days and again within 24 hours prior to prescribe lenalidomide for cycle 1 (prescriptions must be filled within 7 days as required by Revlimid REMS) 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 Exclusion Criteria: Known sensitivity to lenalidomide or other thalidomide derivatives or anti cluster of differentiation (CD)20 Documented prolymphocytic leukemia (prolymphocytes more than 55% in the blood) Known history of infection with human immunodeficiency virus (HIV) or human T cell leukemia virus 1 (HTLV-1) Serologic status reflecting active hepatitis B or C; patients with hepatitis B (HBV) antibody positive but who have positivity for hepatitis B surface antigen (HBsAg) or anti hepatitis B core antibody (anti-HBc) and patients who are positive for anti-hepatitis C (HCV) will need to have a negative polymerase chain reaction (PCR) (viral HBV deoxyribonucleic acid [DNA] or HCV ribonucleic acid [RNA]) result prior to enrollment; those who are HBsAg positive or HBV DNA positive and those who are positive for HCV (RNA) will be excluded Pregnant or breast feeding females History of tuberculosis treated within the last five years or recent exposure to tuberculosis Any serious medical condition, laboratory abnormality, or psychiatric illness that places the subject unacceptable risk if he/she were to participate to the study Patients with a recent history of deep vein thrombosis or pulmonary embolus, in the six months prior to enrollment are not eligible for this study

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: Treatment (lenalidomide, obinutuzumab)<br>Patients receive obinutuzumab IV over 3-4 hours on days 1, 2, 8, and 15 of course 1 and day 1 of courses 2-6 and lenalidomide PO QD on days 9-28 of course 1 and days 1-28 of all subsequent courses. Treatment with obinutuzumab repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may continue to receive lenalidomide PO QD in the absence of disease progression or unacceptable toxicity. | Drug: Lenalidomide<br>* Given PO<br>* Other names: Revlimid;Biological: Obinutuzumab<br>* Given IV<br>* Other names: RO 5072759;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Response | Response is Complete Response or Partial Response. CR is absence of Lymphadenopathy, Hepatomegaly or Splenomegaly, lymphocytes < 4000/ul, normocellular, <30% lymphocytes, no B-lymphoid nodules, Platelets > 100,000/ul, hemoglobin >11.0 g/dl and Neutrophils >1500/ul. PR is >/= 50% decrease in lymphadenopathy, hepatomegaly, splenomegaly and Blood Lymphocytes from baseline, 50% reduction in marrow infiltrate or B-lymphoid nodules. Platelet count > 100,000/ul, Hemoglobin > 11 g/dl and Neutrophils >1500/ul or increase >/= 50% of all over base. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Next Treatment | The time-to-event outcomes (such as time to next treatment or overall survival). Time to Next Treatment is from start of study medication to the start of the next treatment, or last follow up if no next therapy. | Up to 5 years, 2 months | 
| Overall Survival | Time from date of treatment start until date of death due to any cause or last Follow-up. Survival will be measured by the estimated median survival computed by Kaplan-Meier (K-M) analysis, which is the time point at which the cumulative survival drops below 50%, if present. If not present then the median Overall Survival is not reached and not available (NA) as there are an insufficient number of participants with events. In either case ranges are provided for observed survival intervals used in the K-M analysis. | Up to 5 years, 2 months |