Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, Untreated Chronic Lymphocytic Leukemia, Vitamin D Deficiency
Conditions
Brief summary
This randomized pilot early phase I trial studies how well cholecalciferol works in treating patients with newly diagnosed non-Hodgkin lymphoma or chronic lymphocytic leukemia with low levels of vitamin D (vitamin D deficiency). Cholecalciferol may increase levels of vitamin D and improve survival in patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia receiving standard of care chemotherapy.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the 3 year progression-free survival (PFS), defined as time from the time of study entry of watch and wait or newly diagnosed non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) until relapse, progression, or death from any cause. SECONDARY OBJECTIVES: I. To evaluate changes in the levels of serum vitamin D levels during therapy with daily oral vitamin D supplementation (cholecalciferol). II. To evaluate the overall survival (OS), defined as time from the time of study entry of watch and wait patients or newly diagnosed NHL or CLL until death from any cause. OUTLINE: Patients with low levels of vitamin D are randomized to 1 of 2 arms and patients with normal levels are assigned to Arm III. ARM I: Patients receive high-dose cholecalciferol orally (PO) daily for 3 years in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive low-dose cholecalciferol PO daily for 3 years in the absence of disease progression or unacceptable toxicity. ARM III: Patients receive no intervention.
Interventions
DIETARY_SUPPLEMENTCholecalciferol
Given PO
OTHERLaboratory Biomarker Analysis
Optional correlative studies
Sponsors
University of Nebraska
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically confirmed newly diagnosed or previously untreated (patients may be under no treatment ?wait and watch? or have received two cycles of chemotherapy or localized radiation therapy before going on this study) non-Hodgkin?s lymphoma or CLL * Patients must have serum 25-hydroxyvitamin D (25\[OH\]D) drawn at time of enrollment; (NOTE: subjects currently taking vitamin D supplements are eligible for screening) * Simultaneous participation in other therapeutic clinical trials will be allowed * Patients must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts
Exclusion criteria
* History of uncontrollable allergic reactions to vitamin D * History of Paget?s disease * Hypercalcemia * Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the investigator?s opinion, may interfere with protocol adherence or a subject?s ability to give informed consent * Inability to cooperate with the requirements of the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Time from the time of study entry of watch and wait or diagnosed non-Hodgkin lymphoma or chronic lymphocytic leukemia until relapse, progression, or death from any cause, assessed at 3 years | The 3-year progression-free survival will be presented using Kaplan-Meier curves and will be presented for the normal serum vitamin D control group and the low and high dose randomized groups. Each randomized group (low and high dose) will be compared to a historical fixed expected 3-year progression-free survival of 45% using a one-sample logrank test following the method of Woolson (1981). Progression was determined by Investigator assessment based on clinical evidence of disease relapse, progression requiring new therapy, or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events and Serious Events Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 | Up to 30 days | Will be described for the low dose and high dose groups and compared between groups using a Chi-square. The frequency of occurrence of overall toxicity, categorized by toxicity grades, will be described for the low dose and high dose groups and compared between groups using a Chi-square. |
| Overall Survival | Time from the time of study entry of watch and wait or newly diagnosed non-Hodgkin lymphoma or chronic lymphocytic leukemia administered on trial until death from any cause, assessed at 3 years | The 3-year overall survival will be presented using Kaplan-Meier curves and will be presented for the normal serum vitamin D control group and the low and high dose randomized groups. Each randomized group (low and high dose) will be compared to a historical fixed expected 3-year overall survival of 80% using a one-sample logrank test following the method of Woolson (1981). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJulie M Vose, MD, MBA
University of Nebraska
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 12.81 |
| BMI | 32.7 kg/m2 STANDARD_DEVIATION 7.64 |
| Disease Group, n(%) Aggressive | 13 Participants |
| Disease Group, n(%) Indolent | 84 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 173 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 participants |
| Race/Ethnicity, Customized Asian | 0 participants |
| Race/Ethnicity, Customized Black or African American | 6 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 participants |
| Race/Ethnicity, Customized Other | 2 participants |
| Race/Ethnicity, Customized White | 33 participants |
| Serum 25-Hydroxyvitamin D | 20.1 ng/ml STANDARD_DEVIATION 6.52 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 19 Participants |
| Weight, kg | 99.1 kg STANDARD_DEVIATION 30.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 35 | 6 / 36 | 1 / 108 |
| other Total, other adverse events | 1 / 35 | 0 / 36 | 0 / 108 |
| serious Total, serious adverse events | 0 / 35 | 0 / 36 | 0 / 108 |
Outcome results
None listed