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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (curcumin, cholecalciferol) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| curcumin | Drug | Given PO |
|
|
| 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 |
| 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) |
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Inclusion Criteria:
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:
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
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| Name | Affiliation | Role |
|---|---|---|
| Paolo Caimi | Case Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Case Comprehensive Cancer Center | Cleveland | Ohio | 44106-5065 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 2, 2018 |
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| cholecalciferol | Dietary Supplement | Given PO |
|
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| laboratory biomarker analysis | Other | Correlative studies |
|
| pharmacological study | Other | Correlative studies |
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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 |
| COMPLETED |
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| NOT COMPLETED |
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Participants enrolled in study
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants | Participants |
| ||||||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Participants enrolled in study | Posted | Number | percentage of participants | Up to 2 years |
|
|
| ||||||||||||||||||||||||||
| 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. | 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. | Posted | Median | Full Range | Months | Up to 2 years |
|
| ||||||||||||||||||||||||||
| 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 | Participants enrolled in study | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 2 years |
|
| ||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) | Number of participants still alive at 2 years after treatment discontinuation. | Participants enrolled on study. | Posted | Number | participants | Up to 2 years |
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| Secondary | Duration of Response | Time from achievement of partial response, complete response or biologic response to disease progression | No participants analyzed because there was no therapeutic response | Posted | Up to 2 years |
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| |||||||||||||||||||||||||||||
| Post-Hoc | Median Overall Survival (OS) | Number of participants still alive at 2 years after treatment discontinuation. | Participants who received the Curcumin and Cholecalciferol treatment | Posted | Count of Participants | Participants | Up to 2 years post-treatment |
|
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Through study completion, which was an average of 4 years.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 1 | 35 | 1 | 35 | 33 | 35 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Hearing Impaired | Ear and labyrinth disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Intermittent night sweats | Endocrine disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Hypothyroidism | Endocrine disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Blurred vision | Eye disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Bloating | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Stomach cramps | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Stool color change | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Rectal pain | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Chills | General disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Edema limbs | General disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Fatigue | General disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Fever | General disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Flu like symptoms | General disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Malaise | General disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Pain | General disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Infection under chin | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
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| Lymph gland infection | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
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| Nail infection | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
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| Papulopustular rash | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
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| Sinusitis | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
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| Skin infection | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
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| Tooth infection | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
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| Upper respiratory infection | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
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| Urinary tract infection | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
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| Bruising | Injury, poisoning and procedural complications | CTCAE v4.0 | Non-systematic Assessment |
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| Alanine aminotransferase increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
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| Alkaline phosphatase increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
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| Blood bilirubin increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
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| Creatinine increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
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| White blood cell count increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
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| Lymphocyte count decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
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| Lymphocyte count increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
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| Neutrophil count decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
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| Platelet count decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
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| Weight gain | Investigations | CTCAE v4.0 | Non-systematic Assessment |
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| Weight loss | Investigations | CTCAE v4.0 | Non-systematic Assessment |
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| White blood cell decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
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| Anorexia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Hypercalcemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Hyperglycemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Hyperkalemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Hypernatremia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Hyperuricemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Hypocalcemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Hyponatremia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
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| low vitamin D level | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Bone pain | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Night sweats | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Dysesthesia | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Flu like symptoms, body aches | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Sinus pain | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Depression | Psychiatric disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Chronic kidney disease | Renal and urinary disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Hematuria | Renal and urinary disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Dysuria | Renal and urinary disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Allergic rhinitis | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Productive cough | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Chest congestion | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Brittle nails | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Skin integrity | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Hot flashes | Vascular disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Hypertension | Vascular disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Night sweats | Vascular disorders | CTCAE v4.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Paolo Caimi | University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center | 1-800-641-2422 | paolo.caimi@uhhospitals.org |
| May 31, 2022 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D003474 | Curcumin |
| D002762 | Cholecalciferol |
| ID | Term |
|---|---|
| D036381 | Diarylheptanoids |
| D006536 | Heptanes |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |
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| Title | Measurements |
|---|---|
|
| 70-79 years |
|
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
|
| Unknown or Not Reported |
|
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