Azadirachta Indica in Treating Patients With Chronic Lymphocytic Leukemia

Phase 1

Withdrawn

• Conditions: Refractory Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia
• Interventions: 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

• Registration Number: NCT01251250
• Lead Sponsor: Roswell Park Cancer Institute

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.

Study Timeline

• Study First Submitted: 2010-11-30
• Study First Submitted QC: 2010-11-30
• Study Start: 2010-12
• Study First Posted: 2010-12-01
• Primary Completion: 2011-07
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-10
• Last Update Posted: 2014-01-13

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	laboratory biomarker analysis	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.
Arm I	western blotting	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.
Arm I	azadirachta indica	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.
Arm I	pharmacological 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.
Arm I	flow cytometry	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.
Arm I	fluorescence in situ hybridization	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.
Arm I	reverse transcriptase-polymerase chain reaction	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.
Arm I	gene expression analysis	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.

Primary Outcome Measures

Name	Time	Method
Lowest clinically active and tolerable dose	After patients have completed at least 2 treatment courses