Clinical Trials /

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

NCT01787409

Description:

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.

Related Conditions:
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-Cell Lymphoma
  • B-Cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma
  • B-Cell Non-Hodgkin Lymphoma
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Mature T-Cell and NK-Cell Lymphoma/Leukemia
  • Mediastinal Large B-Cell Lymphoma
  • Peripheral T-Cell Lymphoma
  • T-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: LS1293
  • SECONDARY ID: NCI-2013-00037
  • SECONDARY ID: LS1293
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT01787409

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

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (cholecalciferol)ExperimentalVitamin D sufficient patients receive no intervention. Vitamin D insufficient patients receive cholecalciferol PO once weekly for 12 weeks and then once monthly for a total of 36 months.

    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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Event free survival (EFS) (Study I)
    Time Frame: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
    Safety Issue:
    Description: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 Outcome Measures

    Measure:Bio-R response rate (Study II)
    Time Frame:Up to 5 years
    Safety Issue:
    Description: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.
    Measure:EFS time (Study I)
    Time Frame: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
    Safety Issue:
    Description: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.
    Measure:OS (Study II)
    Time Frame:From registration to death due to any cause, assessed up to 5 years
    Safety Issue:
    Description: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-)].
    Measure:Overall response rate (Study II)
    Time Frame:Up to 5 years
    Safety Issue:
    Description: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.
    Measure:Overall survival (OS) time (Study I)
    Time Frame:From registration to death due to any cause, assessed up to 5 years
    Safety Issue:
    Description: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-)].
    Measure:Time to first treatment (Study II)
    Time Frame:From study registration to initiation of anti-CLL therapy, assessed up to 5 years
    Safety Issue:
    Description: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-)].

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Mayo Clinic

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