Clinical trial NCT01787409: Cholecalciferol in Improving Survival in Patients With Newly Diagnosed Cancer With Vitamin D Insufficiency
Official title: Effect of Vitamin D Replacement on Tumor Response and Survival Parameters for Vitamin D Insufficient Patients With Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: 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
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-02-08
Enrollment: 565
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Event free survival (EFS) (Study I)
timeFrame: 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
measure: Treatment free status (Study II)
timeFrame: At 36 months
Secondary outcomes:
measure: Bio-R response rate (Study II)
timeFrame: Up to 5 years
measure: EFS time (Study I)
timeFrame: 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
measure: OS (Study II)
timeFrame: From registration to death due to any cause, assessed up to 5 years
measure: Overall response rate (Study II)
timeFrame: Up to 5 years
measure: Overall survival (OS) time (Study I)
timeFrame: From registration to death due to any cause, assessed up to 5 years
measure: Time to first treatment (Study II)
timeFrame: From study registration to initiation of anti-CLL therapy, assessed up to 5 years
Other outcomes:
measure: Gene expression profiles
timeFrame: Baseline
measure: Immune effector cell levels
timeFrame: Up to 36 months
measure: Serum cytokine profile
timeFrame: Up to 36 months
measure: Vitamin D metabolism single nucleotide polymorphisms (SNPs)
timeFrame: Up to 36 months
measure: Vitamin D receptor expression on tumor cells
timeFrame: Baseline
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Mayo Clinic
name: Thomas E. Witzig, MD
role: PRINCIPAL_INVESTIGATOR
References: