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

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)

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.

Study Overview

• Status: Completed
• Conditions: Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage I Small Lymphocytic Lymphoma
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Dietary supplement: cholecalciferol; Drug: curcumin

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106-5065
      • Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Dietary supplement: cholecalciferol; Given PO; Other Names: Vitamin D3; Calciol; Drug: curcumin; Given PO; Other Names: C.I. 75300; C.I. Natural Yellow 3; Diferuloylmethane; CU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate Based on NCI-WG (for CLL) and Cheson Criteria (for SLL)	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	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Cytotoxic Treatment (TFCT)	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.	Up to 2 years
Percent of Participants With Progression Free Survival (PFS)	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	Up to 2 years
Overall Survival (OS)	Number of participants still alive at 2 years after treatment discontinuation.	Up to 2 years
Duration of Response	Time from achievement of partial response, complete response or biologic response to disease progression	Up to 2 years

Collaborators and Investigators

• Sponsor: Paolo Caimi, MD
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Paolo Caimi, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2014
• Primary Completion (Actual): April 4, 2018
• Study Completion (Actual): December 13, 2018

Study Registration Dates

• First Submitted: March 27, 2014
• First Submitted That Met QC Criteria: March 27, 2014
• First Posted (Estimated): April 1, 2014

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: March 17, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; Leukemia, B-Cell; Chronic Disease; Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Curcumin
• Other Study ID Numbers: CASE5913 (Case Comprehensive Cancer Center); P30CA043703 (U.S. NIH Grant/Contract); NCI-2014-00266 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No