Contiguous Stage II Small Lymphocytic Lymphoma, Noncontiguous Stage II Small Lymphocytic Lymphoma, Stage 0 Chronic Lymphocytic Leukemia, Stage I Chronic Lymphocytic Leukemia, Stage II Chronic Lymphocytic Leukemia, Stage I Small Lymphocytic Lymphoma
Conditions
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.
Interventions
DRUGcurcumin
Given PO
DIETARY_SUPPLEMENTcholecalciferol
Given PO
OTHERlaboratory biomarker analysis
Correlative studies
OTHERpharmacological study
Correlative studies
Sponsors
Paolo Caimi, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| Overall Survival (OS) | Up to 2 years | Number of participants still alive at 2 years after treatment discontinuation. |
| Duration of Response | Up to 2 years | Time from achievement of partial response, complete response or biologic response to disease progression |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
curcumin: Given PO
cholecalciferol: Given PO
laboratory biomarker analysis: Correlative studies
pharmacological study: Correlative studies | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Treatment (Curcumin, Cholecalciferol) |
|---|---|
| Age, Customized 40-49 years | 1 Participants |
| Age, Customized 50-59 years | 17 Participants |
| Age, Customized 60-69 years | 12 Participants |
| Age, Customized 70-79 years | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Region of Enrollment United States | 35 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 35 |
| other Total, other adverse events | 33 / 35 |
| serious Total, serious adverse events | 1 / 35 |
Outcome results
Primary
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
Time frame: Up to 2 years
Population: Participants enrolled in study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Curcumin, Cholecalciferol) | Overall Response Rate Based on NCI-WG (for CLL) and Cheson Criteria (for SLL) | 0 percentage of participants |
Secondary
Duration of Response
Time from achievement of partial response, complete response or biologic response to disease progression
Time frame: Up to 2 years
Population: No participants analyzed because there was no therapeutic response
Secondary
Overall Survival (OS)
Number of participants still alive at 2 years after treatment discontinuation.
Time frame: Up to 2 years
Population: Participants enrolled on study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Curcumin, Cholecalciferol) | Overall Survival (OS) | 35 participants |
Secondary
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
Time frame: Up to 2 years
Population: Participants enrolled in study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Curcumin, Cholecalciferol) | Percent of Participants With Progression Free Survival (PFS) | 57.5 percentage of participants |
Secondary
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.
Time frame: Up to 2 years
Population: Evaluable participants who progressed. Two additional participants were recorded to have progressed but data are missing regarding TFCT and all efforts to retrieve information have been exhausted.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Curcumin, Cholecalciferol) | Time to First Cytotoxic Treatment (TFCT) | 10.5 Months |
Post Hoc
Median Overall Survival (OS)
Number of participants still alive at 2 years after treatment discontinuation.
Time frame: Up to 2 years post-treatment
Population: Participants who received the Curcumin and Cholecalciferol treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Curcumin, Cholecalciferol) | Median Overall Survival (OS) | 35 Participants |