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

Sponsor

Paolo Caimi, MD (Other)

Overall Status

Completed

CT.gov ID

NCT02100423

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

50.6

Actual Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: curcumin Dietary Supplement: cholecalciferol Other: laboratory biomarker analysis Other: pharmacological study	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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:

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Sep 26, 2014

Actual Primary Completion Date :

Apr 4, 2018

Actual Study Completion Date :

Dec 13, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (curcumin, cholecalciferol) 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 Given PO Other Names: C.I. 75300 C.I. Natural Yellow 3 CU Diferuloylmethane Dietary Supplement: cholecalciferol Given PO Other Names: Calciol Vitamin D3 Other: laboratory biomarker analysis Correlative studies Other: pharmacological study Correlative studies Other Names: pharmacological studies

Arm

Intervention/Treatment

Experimental: Treatment (curcumin, cholecalciferol)

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

Given PO

Other Names:

C.I. 75300

C.I. Natural Yellow 3

Diferuloylmethane

Dietary Supplement: cholecalciferol

Given PO

Other Names:

Calciol

Vitamin D3

Other: laboratory biomarker analysis

Correlative studies

Other: pharmacological study

Correlative studies

Other Names:

pharmacological studies

Outcome Measures

Primary Outcome Measures

Overall response rate (biologic response rate + complete response [CR] + partial response [PR]) based on NCI-WG (for CLL) and Cheson criteria (for SLL) [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]
The point estimate of the overall response rate and biologic response rate along with 95% confidence intervals will be calculated using binomial distribution theory.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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