Azadirachta Indica in Treating Patients With Chronic Lymphocytic Leukemia
Primary Purpose
Refractory Chronic Lymphocytic Leukemia, Stage II Chronic Lymphocytic Leukemia, Stage III Chronic Lymphocytic Leukemia
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
laboratory biomarker analysis
western blotting
gene expression analysis
pharmacological study
flow cytometry
fluorescence in situ hybridization
azadirachta indica
reverse transcriptase-polymerase chain reaction
Sponsored by
About this trial
This is an interventional treatment trial for Refractory Chronic Lymphocytic Leukemia
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm I
Arm Description
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.
Outcomes
Primary Outcome Measures
Lowest clinically active and tolerable dose
Secondary Outcome Measures
Full Information
NCT ID
NCT01251250
First Posted
November 30, 2010
Last Updated
January 10, 2014
Sponsor
Roswell Park Cancer Institute
1. Study Identification
Unique Protocol Identification Number
NCT01251250
Brief Title
Azadirachta Indica in Treating Patients With Chronic Lymphocytic Leukemia
Official Title
Phase I Clinical Trial of Neem Leaf Extract for the Treatment of Chronic Lymphocytic Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Withdrawn
Why Stopped
lost sponsor support
Study Start Date
December 2010 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Chronic Lymphocytic Leukemia, Stage II Chronic Lymphocytic Leukemia, Stage III Chronic Lymphocytic Leukemia, Stage IV Chronic Lymphocytic Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
western blotting
Other Intervention Name(s)
Blotting, Western, Western Blot
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
gene expression analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
flow cytometry
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
fluorescence in situ hybridization
Other Intervention Name(s)
fluorescence in situ hybridization (FISH)
Intervention Description
Correlative studies
Intervention Type
Biological
Intervention Name(s)
azadirachta indica
Other Intervention Name(s)
neem, neem tree
Intervention Description
Given orally
Intervention Type
Genetic
Intervention Name(s)
reverse transcriptase-polymerase chain reaction
Other Intervention Name(s)
RT-PCR
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Lowest clinically active and tolerable dose
Time Frame
After patients have completed at least 2 treatment courses
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Asher Chanan-Khan
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Azadirachta Indica in Treating Patients With Chronic Lymphocytic Leukemia
We'll reach out to this number within 24 hrs