Study Examining the Combination of Revlimid (Lenalidomide)and Vidaza (Azacitidine) for Relapsed/Refractory CLL and SLL

Study Overview
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Brief Summary
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To determine the response to the combination of Revlimid (Lenalidomide)+ Vidaza (Azacitidine) in patients with relapsed/refractory CLL and SLL Hypothesis- lenalidomide's activity in combination with azacitidine may further enhance its activity and the durability of treatment response.

Detailed Description
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Treatment response of lenalidomide's activity in combination with azacitidine may further enhance its activity and the durability of treatment response.

Official Title
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A Phase II, Single Arm Study Examining the Combination of Revlimid (Lenalidomide) and Vidaza (Azacitidine) (RA-CLL) for the Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)

Conditions
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Chronic Lymphocytic Leukemia(CLL), Small Lymphocytic Lymphoma

Intervention / Treatment
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* Drug: Revlimid
* Drug: Azacitidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be age ≥ 18 must have an ECOG PS ≤ 2 must understand and voluntarily sign informed consent adhere to the study protocol requirements and schedule must carry the diagnosis of B-CLL/SLL, SLL/CLL must be defined as relapsed or refractory disease Pts. must have received and failed at least one purine-based treatment regimen (ie. FCR, FR, PCR, Fludarabine) or alemtuzumab-based regimen or bendamustine-based regimen prior to study enrollment Serum bilirubin levels <1.5 times the upper limit of the normal range for the laboratory (ULN) Higher levels are acceptable if these can be attributed to active hemolysis, ineffective erythropoiesis or Gilbert's disease.Serum (SGOT) [AST])(SGPT) [ALT]) levels <2 x ULN or <5 x ULN if hepatic metastases are present) Subjects must have calculated creatinine clearance ≥ 30ml/min Absolute neutrophil count > 1.0 x 109 / L Platelet count > 50x 109 / L (unless bone marrow is heavily infiltrated with underlying disease (50% or more) Disease free of prior malignancies for > 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma insitu of the cervix or breast All participants must be registered into the mandatory RevAssist® program Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin) 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. Exclusion Criteria: - Patient must not have any serious medical condition, laboratory abnormality, or psychiatric illness that would places the subject at unacceptable risk or confound the interpretation of data from the study Patients must be lenalidomide / azacitidine naïve prior to study enrollment Patients must not be HIV, Hepatitis B or Hepatitis C positive, except for Patients who are seropositive because of hepatitis B virus vaccine are eligible Patients must not have received chemotherapy, immunotherapy or any experimental study drug for CLL or SLL at least 4 weeks prior to study enrollment and initiation of treatment Patients with history of B-CLL and the development of prolymphocytic leukemia or Richter's transformation Known or suspected hypersensitivity to azacitidine, mannitol, thalidomide or Lenalidomide Pregnant or breast feeding females are not eligible or lactating females must agree not to breast feed while taking Lenalidomide Evidence of laboratory TLS by Cairo-Bishop Definition of Tumor Lysis Syndrome Subjects may be enrolled upon correction of electrolyte abnormalities Patients with advanced malignant hepatic tumors; Concurrent use of other anti-cancer agents or treatments, or Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.

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: response to Vidaza + Revlimid<br>response to combination of azacitidine + lenalidomide A Phase II, Single Arm Study Examining the Combination of Revlimid (Lenalidomide) and Vidaza (Azacitidine) (RA-CLL) for the Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) | Drug: Revlimid<br>* Lenalidomide PO daily Day 1-21. For patients with baseline calculated creatinine clearance ≥ 30 ml/min and < 60 ml/min the starting dose is 5 mg every other day (odd numbered days during Days 1-21). For patients with baseline calculated creatinine clearance ≥ 60 ml/min the starting dose is 5 mg daily on Days 1-21).<br>* Other names: Lenalidomide;Drug: Azacitidine<br>* Azacitidine 75 mg/m2 IV or SC D 1-5<br>* Other names: Vidaza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Rate of Response to the Combination of Azacitidine + Lenalidomide in Select Patients | the rate of response to the combination of azacitidine + lenalidomide in select patients with relapsed/refractory CLL and small lymphocytic lymphoma (SLL). | 9 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess for Treatment Related Toxicity Following Administration of Lenalidomide/ Azacitidine. |  | 30 days after treatment completion (up to 10 Months) | 
| The Progression Free Survival of Patients Treated With the Combination of Lenalidomide and Azacitidine |  | 9 Months | 
| The Overall Survival of Patients Treated With the Combination of Lenalidomide and Azacitidine |  | 9 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic lymphocytic leukemia (CLL), Small Lymphocytic Lymphoma