Azadirachta Indica in Treating Patients With Chronic Lymphocytic Leukemia

NCT ID: NCT01251250

Last Updated: 2014-01-13

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31

Brief Summary

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

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.

Conditions

Refractory Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

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.

Group Type: EXPERIMENTAL

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

western blotting

Intervention Type: GENETIC

Correlative studies

gene expression analysis

Intervention Type: GENETIC

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

flow cytometry

Intervention Type: OTHER

Correlative studies

fluorescence in situ hybridization

Intervention Type: GENETIC

Correlative studies

azadirachta indica

Intervention Type: BIOLOGICAL

Given orally

reverse transcriptase-polymerase chain reaction

Intervention Type: GENETIC

Correlative studies

Interventions

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

western blotting

Correlative studies

Intervention Type: GENETIC

gene expression analysis

Correlative studies

Intervention Type: GENETIC

pharmacological study

Correlative studies

Intervention Type: OTHER

flow cytometry

Correlative studies

Intervention Type: OTHER

fluorescence in situ hybridization

Correlative studies

Intervention Type: GENETIC

azadirachta indica

Given orally

Intervention Type: BIOLOGICAL

reverse transcriptase-polymerase chain reaction

Correlative studies

Intervention Type: GENETIC

Other Intervention Names

Blotting, Western; Western Blot; pharmacological studies; fluorescence in situ hybridization (FISH); neem; neem tree; RT-PCR

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roswell Park Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Asher Chanan-Khan

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Other Identifiers

NCI-2010-02103

Identifier Type: -

Identifier Source: secondary_id

I 169009

Identifier Type: -

Identifier Source: org_study_id