Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Study Overview
=================
Brief Summary
-----------------
This phase II trial studies the efficacy (activity), and tolerability of curcumin and cholecalciferol combination in treating patients with previously untreated stage 0-II chronic lymphocytic leukemia or small lymphocytic lymphoma. Curcumin and cholecalciferol may prevent or slow the growth of cancer cells.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To determine the overall response rate (ORR) based on National Cancer Institute-Working Group (NCI-WG) criteria in chronic lymphocytic leukemia (CLL) or the Cheson criteria in small lymphocytic lymphoma (SLL). SECONDARY OBJECTIVES: I. To determine the time to first cytotoxic treatment (TFCT), progression free survival (PFS), and overall survival (OS) using this regimen. OUTLINE: Patients receive curcumin orally (PO) daily on days 1-28 and cholecalciferol PO daily on days 8-28 of course 1 and days 1-28 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving partial response or better may receive treatment for a total of 2 years. After completion of study treatment, patients are followed up for 30 days and then every 3-6 months for 2 years.

Official Title
-----------------
A Phase II Study of Curcumin and Vitamin D in Previously Untreated Patients With Early Stage Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Conditions
-----------------
Contiguous Stage II Small Lymphocytic Lymphoma, Noncontiguous Stage II Small Lymphocytic Lymphoma, Stage 0 Chronic Lymphocytic Leukemia, Stage I Chronic Lymphocytic Leukemia, Stage I Small Lymphocytic Lymphoma, Stage II Chronic Lymphocytic Leukemia

Intervention / Treatment
-----------------
* Drug: curcumin
* Dietary Supplement: cholecalciferol
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have a diagnosis of CLL based on peripheral blood flow cytometry and/or bone marrow aspiration and biopsy OR diagnosis of SLL based on lymph node or bone marrow biopsy; patients with SLL need to have measurable disease Performance status (Eastern Cooperative Oncology Group [ECOG]) 0-2 Patients must have not received any prior treatment for CLL or SLL Patients must be stage 0-II based on Rai staging system; must have no indication for treatment for SLL per NCI-WG criteria Absolute neutrophil count (ANC) >= 1,500/mm^3 Platelet count >= 100,000/mm^3 Hemoglobin >= 10 g/dL Serum creatinine =< 2.0 g/dL or calculated creatinine clearance (CrCl) >= 60mL/min (Cockcroft-Gault method) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal (ULN) Bilirubin < 2.0 x ULN, unless subject has Gilbert's disease Calcium < 10.1 mg/dL (corrected to serum albumin) Females will be either postmenopausal for at least 1 year or surgically sterile for at least 3 months OR females of child-bearing potential must have a negative pregnancy test at screening and agree to take appropriate precautions to avoid pregnancy (double barrier method of birth control or abstinence) from screening through 3 months after the last dose of treatment Able to comprehend and willing to sign an Informed Consent Form (ICF) Subjects must be off any steroids 7 days prior to the initiation of treatment Subjects must be off any curcumin, tumeric, or vitamin D supplements for 14 days prior to the initiation of treatment Subjects must be able to take oral medications Exclusion Criteria: Presence of malignancy (other than the one treated in this study) which required systemic treatment within the past 3 years Any indication to start treatment for CLL based on NCI-WG criteria Prior therapy for CLL/SLL Subjects who are pregnant or breast-feeding; breastfeeding should be discontinued if the mother is treated with curcumin Concurrent medical condition which may increase the risk of toxicity, including: Hypercalcemia of any cause Untreated hyperparathyroidism Paget's disease of bone Uncontrolled intercurrent illness including, but not limited to, ongoing active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician; subjects receiving antibiotics that are under control may be included in the study Inability to take oral medications Patients receiving other investigational agent History of allergic reactions attributed to compounds of similar chemical or biologic composition to curcumin or vitamin D or other agents used in this study Patients on therapeutic anticoagulation, with heparin (or low-molecular weight heparin), warfarin, or a direct thrombin inhibitor as the safety of concurrent administration of curcumin has not been established Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (curcumin, cholecalciferol)<br>Patients receive curcumin PO daily on days 1-28 and cholecalciferol PO daily on days 8-28 of course 1 and days 1-28 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving partial response or better may receive treatment for a total of 2 years. | Drug: curcumin<br>* Given PO<br>* Other names: Diferuloylmethane;Dietary Supplement: cholecalciferol<br>* Given PO<br>* Other names: Vitamin D3;Other: laboratory biomarker analysis<br>* Correlative studies<br>Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (biologic response rate + complete response [CR] + partial response [PR]) based on NCI-WG (for CLL) and Cheson criteria (for SLL) | The point estimate of the overall response rate and biologic response rate along with 95% confidence intervals will be calculated using binomial distribution theory. | The time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first cytotoxic treatment | Kaplan-Meier method and Cox proportional hazard model will be used for the data analysis. | Time from entry onto study until initiation of treatment with cytotoxic agents because of disease progression, assessed up to 2 years | 
| Progression free survival | Kaplan-Meier method and Cox proportional hazard model will be used for the data analysis. | Time from entry onto study until CLL/SLL progression or death from any cause, assessed up to 2 years | 
| Overall survival | Kaplan-Meier method and Cox proportional hazard model will be used for the data analysis. | Up to 2 years | 
| Duration of response |  | Up to 2 years |