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.
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:
P50CA097274
- 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
| Name | Type | Description | Interventions |
|---|
| Treatment (cholecalciferol) | Experimental | Vitamin 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 |
Last Updated
April 6, 2021
