Cholecalciferol in Improving Survival in Patients With Newly Diagnosed Cancer With Vitamin D Insufficiency

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.

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