Azadirachta Indica in Treating Patients With Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Azadirachta indica may be an effective treatment for chronic lymphocytic leukemia. PURPOSE: This phase I trial is studying the side effects and best dose of Azadirachta indica in treating patients with chronic lymphocytic leukemia.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the lowest dose of neem leaf extract (NLE) with antileukemic effect and acceptable toxicity in patients with chronic lymphocytic leukemia (CLL). II. Establish the safety and toxicity of NLE in patients with CLL. SECONDARY OBJECTIVES: I. Determine the efficacy of NLE in patients with CLL defined as overall clinical response (CR + PR) by the IWCLL criterion. II. To develop a pharmacokinetic/pharmacodynamic model relating neem leaf extract exposure to toxicity and pharmacodynamic endpoints in CLL patients that will allow personalized dosing to target optimal drug exposure. III. To conduct correlative studies. OUTLINE: This is a dose-escalation study. Patients receive oral Azadirachta indica once daily on days 1-28. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year.

Official Title
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Phase I Clinical Trial of Neem Leaf Extract for the Treatment of Chronic Lymphocytic Leukemia

Conditions
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Refractory Chronic Lymphocytic Leukemia, Stage II Chronic Lymphocytic Leukemia, Stage III Chronic Lymphocytic Leukemia, Stage IV Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Other: laboratory biomarker analysis
* Genetic: western blotting
* Genetic: gene expression analysis
* Other: pharmacological study
* Other: flow cytometry
* Genetic: fluorescence in situ hybridization
* Biological: azadirachta indica
* Genetic: reverse transcriptase-polymerase chain reaction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a definitive diagnosis of CLL as defined by the IWCLL criteria Patients may not have received any prior treatment for management of CLL; (no more than 30 patients with treatment naive disease will be included in this study) Patients with advance stage disease (Rai Stage II-IV) may be included in this clinical trial if they refuse to take standard chemotherapeutic regimens Patients with relapsed or relapsed/ resistant may be included in this clinical trial if they refuse to take standard chemotherapeutic regimens Patients must understand and voluntarily sign an informed consent form Have an ECOG Performance Status of =< 2 at study entry Able to adhere to the study visit schedule and other protocol requirements Leukocytes >= 3,000/mcL Absolute neutrophil count >= 1,500/mcL Hemoglobin >= 10g/dl Platelets >= 50,000/mcl Total bilirubin within normal institutional limits AST (SGOT)/ ALT (SGPT) =< 2.5 X institutional ULN Patients of childbearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form 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 Trying to conceive, pregnant or breast feeding female patients Unwilling or unable to follow protocol requirements Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug Patients who are consuming other herbals or non-traditional therapies (i.e. green tea extracts and cumin) within the last 4 weeks(28 days) of initiating this clinical study; note: patient must have stopped herbal or other non-traditional therapies for CLL at least 28 days prior to initiating therapy on this study Patients with high-risk cytogenetic (del 17p, del 11q) determined by FISH analysis Prior organ transplant

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral Azadirachta indica once daily on days 1-28. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. | Other: laboratory biomarker analysis<br>* Correlative studies<br>Genetic: western blotting<br>* Correlative studies<br>* Other names: Western Blot;Genetic: gene expression analysis<br>* Correlative studies<br>Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: flow cytometry<br>* Correlative studies<br>Genetic: fluorescence in situ hybridization<br>* Correlative studies<br>* Other names: fluorescence in situ hybridization (FISH);Biological: azadirachta indica<br>* Given orally<br>* Other names: neem tree;Genetic: reverse transcriptase-polymerase chain reaction<br>* Correlative studies<br>* Other names: RT-PCR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lowest clinically active and tolerable dose |  | After patients have completed at least 2 treatment courses |