Aggressive Non-Hodgkin Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-Cell Lymphoma, Chronic Lymphocytic Leukemia, Diffuse Large B-Cell Lymphoma, Enteropathy-Associated T-Cell Lymphoma, Hepatosplenic T-Cell Lymphoma, Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma, Mediastinal (Thymic) Large B-Cell Lymphoma, Nasal Type Extranodal NK/T-Cell Lymphoma, Peripheral T-Cell Lymphoma, Not Otherwise Specified, Primary Cutaneous Anaplastic Large Cell Lymphoma, Refractory Anaplastic Large Cell Lymphoma, Small Lymphocytic Lymphoma, Subcutaneous Panniculitis-Like T-Cell Lymphoma
Conditions
Brief summary
This partially randomized clinical trial studies cholecalciferol in improving survival in patients with newly diagnosed cancer with vitamin D insufficiency. Vitamin D replacement may improve tumor response and survival and delay time to treatment in patients with cancer who are vitamin D insufficient.
Detailed description
PRIMARY OBJECTIVES: I. To determine if vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated diffuse large B-cell lymphoma (DLBCL) can improve event free survival at 12 months to be equivalent to that of a control population of vitamin D sufficient patients. (Study I) II. To assess the percentage of patients requiring treatment with conventional therapy at 36 in months in vitamin D insufficient patients with early stage chronic lymphocytic leukemia (CLL) being managed with observation who undergo vitamin D replacement. (Study II) SECONDARY OBJECTIVES: I. To assess the effect of vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated DLBCL on overall survival. (Study I) II. To assess the effect of vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated DLBCL on event free survival. (Study I) III. To assess the effect of vitamin D replacement in vitamin D insufficient patients with newly diagnosed untreated T cell lymphoma on event free and overall survival. (Study I) IV. To assess the effect of vitamin D replacement in vitamin D insufficient CLL patients on Bio-r response rate and overall response rate. (Study II) V. To assess time to treatment and overall survival in vitamin D insufficient CLL patients who received vitamin D replacement. (Study II) TERTIARY OBJECTIVES: I. To study immune effector cells (lymphocytes, monocytes), serum cytokines, and tumor cells from vitamin D deficient and sufficient patients to learn the effects of vitamin D on both tumor cells and the patient's immune system. (Study I-II) OUTLINE: Vitamin D sufficient patients receive no intervention. Vitamin D insufficient patients receive cholecalciferol orally (PO) once weekly for 12 weeks and then once monthly for a total of 36 months. After completion of study treatment, patients are followed up for 2 years.
Interventions
DIETARY_SUPPLEMENTCholecalciferol
Given PO
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
Mayo Clinic
National Cancer Institute (NCI)
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
* Newly diagnosed aggressive lymphoma or CLL/small lymphocytic lymphoma (SLL) that meets disease specific criteria below: * Study 1 - Aggressive lymphoma * Newly diagnosed de-novo DLBCL or primary mediastinal B-cell lymphoma that will be treated with an anthracycline-containing regimen (rituximab-cyclophosphamide, doxorubicin hydrochloride, prednisone \[R-CHOP\] or equivalent); patients with composite lymphomas can also be enrolled as long as they have large cell component and will be treated with an anthracycline; in addition, patients with "B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma" or post-transplant DLBCL are also eligible as long as they meet other criteria; patients with typical Burkitt lymphoma are not eligible * NOTE: patients can be enrolled up through day 1 of cycle 3 of therapy; the patient is permitted to participate in any other therapeutic therapy for their disease as long as it does not concern vitamin D; patients can begin their chemotherapy while awaiting vitamin D results and treatment arm assignment or * Newly diagnosed untreated peripheral T-cell non-Hodgkin lymphoma (NHL) that will be treated with chemotherapy; NOTE: patients can be enrolled up through day 1 of cycle 3 of therapy; this includes the following disease types: * Peripheral T cell lymphoma, unspecified * Anaplastic large cell lymphoma (T and null cell type) * Extranodal NK/T-cell lymphoma, nasal type * Enteropathy-type T-cell lymphoma * Hepatosplenic T-cell lymphoma * Subcutaneous panniculitis-like T-cell lymphoma * Angioimmunoblastic T-cell lymphoma * Anaplastic large cell lymphoma - primary cutaneous type and * Willing to provide tissue for correlative research purposes * Study 2 - CLL/SLL * Newly diagnosed (\< 12 months from pre-registration on this study) CLL according to the National Cancer Institute (NCI) criteria or SLL according to the World Health Organization (WHO) criteria; this includes previous documentation of: * Biopsy-proven small lymphocytic lymphoma * Diagnosis of CLL according to NCI working group criteria as evidenced by all of the following: * Peripheral blood lymphocyte count of \> 5,000/mm\^3; if present, prolymphocytes should be \< 55% * Immunophenotyping consistent with CLL defined as: * The predominant population of lymphocytes share both B-cell antigens (cluster of differentiation \[CD\]19, CD20, or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.) * Dim surface immunoglobulin expression * Restricted surface kappa or lambda light chain expression * Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescent in situ hybridization (FISH) analysis for t(11;14)(immunoglobulin H \[IgH\]/cyclin D 1 \[CCND1\]) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy * Rai stage 0 or 1 * Previously untreated * Asymptomatic with the plan for observation * Life expectancy of at least 24 months * Willing to provide tissue for correlative research purposes * Both Studies: * Capable of swallowing intact study medication capsules * Serum calcium \< 11 mg/dL; note: patients with hypercalcemia can be enrolled after the calcium is corrected with standard of care treatments * Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) * Note: During the Active Monitoring Phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up * Willing to provide blood samples for correlative research purposes * Vitamin D level (25 hydroxy D2 + hydroxyl D3) confirmed by central laboratory review
Exclusion criteria
* Patients with Burkitt lymphoma or any patient receiving rituximab-cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate / ifosfamide, etoposide, high-dose cytarabine (R- CODOXM/IVAC) * Patients who previously had indolent lymphoma and now at a separate episode have large cell NHL (i.e. transformation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event free survival (EFS) (Study I) | Time from study registration to lymphoma progression, initiation of new anti-lymphoma therapy after completion or cessation of the original anthracycline based treatment, or death due to any cause, assessed at 12 months | The proportion of successes will be estimated separately in the groups by the number of successes divided by the total number of evaluable patients. 95% confidence intervals for the true success proportion will be calculated by the exact binomial method. |
| Treatment free status (Study II) | At 36 months | The proportion of successes will be estimated separately in the groups by the number of successes divided by the total number of evaluable patients. 95% confidence intervals for the true success proportion will be calculated by the exact binomial method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bio-R response rate (Study II) | Up to 5 years | Bio-R response rate will be calculated as the number of patients with Bio-R response divided by the number of evaluable patients. If a sufficient number of Bio-R responses are seen, differences in Bio-R rate between the two study groups will be evaluated using Fisher's exact test. |
| EFS time (Study I) | From study registration to lymphoma progression, initiation of new anti-lymphoma therapy after completion or cessation of the original anthracycline based treatment, or death due to any cause, assessed up to 5 years | The distribution of event-free survival time in each group will be estimated using the method of Kaplan-Meier. Differences between the groups will be evaluated using Cox proportional hazard models. |
| OS (Study II) | From registration to death due to any cause, assessed up to 5 years | The distribution of survival time will be estimated using the method of Kaplan-Meier. Differences between the groups will be evaluated using Cox proportional hazard models. These models will be assessed both unadjusted and adjusted for Rai stage and FISH \[favorable (13q-, +12, no abnormalities) vs. unfavorable (11q-, 17p-)\]. |
| Overall response rate (Study II) | Up to 5 years | Exact binomial 95% confidence intervals for the true overall response rate will be calculated. If a sufficient number of responses are seen, differences in overall response rate between the two study groups will be evaluated using Fisher's exact test. |
| Overall survival (OS) time (Study I) | From registration to death due to any cause, assessed up to 5 years | The distribution of survival time will be estimated using the method of Kaplan-Meier. Differences between the groups will be evaluated using Cox proportional hazard models. These models will be assessed both unadjusted and adjusted for Rai stage and FISH \[favorable (13q-, +12, no abnormalities) vs. unfavorable (11q-, 17p-)\]. |
| Time to first treatment (Study II) | From study registration to initiation of anti-CLL therapy, assessed up to 5 years | The distribution of time to first treatment will be estimated using the method of Kaplan-Meier. Differences between the two study groups will be evaluated using Cox proportional hazard models. These models will be assessed both unadjusted and adjusted for Rai stage and FISH \[favorable (13q-, +12, no abnormalities) vs. unfavorable (11q-, 17p-)\]. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORThomas E. Witzig, MD
Mayo Clinic
Outcome results
None listed