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

Phase 2

Completed

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

Interventions: Drug: curcumin
Dietary Supplement: cholecalciferol
Other: laboratory biomarker analysis
Other: pharmacological study

Registration Number: NCT02100423

Lead Sponsor: Paolo Caimi, MD

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 35

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (curcumin, cholecalciferol)	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.
Treatment (curcumin, cholecalciferol)	laboratory biomarker analysis	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.
Treatment (curcumin, cholecalciferol)	pharmacological study	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.
Treatment (curcumin, cholecalciferol)	curcumin	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.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate Based on NCI-WG (for CLL) and Cheson Criteria (for SLL)	Up to 2 years	The point estimate of the overall response rate (biologic response rate + complete response \[CR\] + partial response \[PR\]) with 95% confidence intervals will be calculated using binomial distribution theory. The time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented and assessed

Secondary Outcome Measures

Name	Time	Method
Percent of Participants With Progression Free Survival (PFS)	Up to 2 years	Percent of participants that reached 2-year survival without disease progression. PFS is defined as the time from entry onto study until CLL/SLL progression or death from any cause. National Cancer Institute Working Group (NCI-WG) criteria is used for CLL participants and Cheson Criteria is used for SLL participants
Duration of Response	Up to 2 years	Time from achievement of partial response, complete response or biologic response to disease progression
Time to First Cytotoxic Treatment (TFCT)	Up to 2 years	TFCT defined as the time from entry onto study until initiation of treatment with cytotoxic agents because of disease progression. Kaplan-Meier method and Cox proportional hazard model will be used for the data analysis.
Overall Survival (OS)	Up to 2 years	Number of participants still alive at 2 years after treatment discontinuation.