VitD3 Supplementation in Patients With Multiple Myeloma

Study Overview
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Brief Summary
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The goal of this clinical trial is to evaluate post-transplant immune reconstitution and lymphocyte recovery as well as the 3-year progression-free survival of patients with multiple myeloma in two treatment arms. One arm will receive lenalidomide and an intensified regimen of maintenance VitD, and the other arm will receive lenalidomide and a therapeutic regimen of VitD. This clinical trial will also evaluate the overall response rate and survival for both treatment arms.

Detailed Description
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Management of multiple myeloma (MM) has changed significantly over the past 10 years. The use of three drug induction therapy followed by autologous stem cell transplantation (ASCT) has become standard of care for transplant eligible patients with MM since randomized trials showed improved progression-free survival (PFS) and overall survival (OS) with three drugs, albeit in the non-transplant setting. Evidence suggests Vitamin D deficiency is correlated with poorer outcomes in this population; however, it is unknown if intensified Vitamin D supplementation improves outcomes. This clinical trial aims to address this question and will postulate the impact of Vitamin D on immunoregulatory functions and the hematopoietic niche microenvironment.

Official Title
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EVALUATION OF CHOLECALCIFEROL (VitD3) MAINTENANCE SUPPLEMENTATION IN PATIENTS WITH MULTIPLE MYELOMA (MM) UNDERGOING TRANSPLANTATION AND IN COMBINATION WITH LENALIDOMIDE MAINTENANCE

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Lenalidomide
* Drug: Vitamin D - Intensified
* Drug: Vitamin D - Therapeutic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of multiple myeloma without amyloidosis. Willing and able to take medication to prevent blood clots (example: aspirin, low molecular weight heparin, etc.) and comply with lenalidomide REMS program requirements. 18 years or older. Eligible for autologous stem cell transplantation or have completed ASCT within 120 days prior to starting the study. Be able to take and swallow oral medication (capsules) whole with no impairment of gastrointestinal function. Exclusion Criteria: Prior transplant (solid organ or stem cell) Known allergy to study drug (cholecalciferol) Other prior cancer diagnosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenalidomide + intensified VitD<br>In this arm, patients will receive the standard lenalidomide dose along with an intensified level of Vitamin D maintenance regimen. | Drug: Lenalidomide<br>* For first three cycles, taken orally once daily for 28 days at 10mg/day dose. After cycle 4, taken orally once daily at 15 mg/day dose<br>* Other names: Revlimid;Drug: Vitamin D - Intensified<br>* After replacement of vitamin D deficiency with weekly cholecalcefirol 50,000 units untill levels are > 30, will start maintenance therapy with Monthly replacement with 50,000 IU<br>* Other names: Cholecalciferol;|
| Active Comparator: Lenalidomide + therapeutic VitD<br>In this arm, patients will receive the standard lenalidomide dose along with a therapeutic level of Vitamin D regimen. | Drug: Lenalidomide<br>* For first three cycles, taken orally once daily for 28 days at 10mg/day dose. After cycle 4, taken orally once daily at 15 mg/day dose<br>* Other names: Revlimid;Drug: Vitamin D - Therapeutic<br>* After replacement of vitamin D deficiency with weekly cholecalcefirol 50,000 units untill levels are > 30, stop replacement and continue monitoring levels<br>* Other names: Cholecalciferol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To describe the lymphocyte subset analysis for the two treatment arms at 120 days post autologous stem cell transplant [120 days] | Evaluate absolute lymphocyte count and the difference in subset analysis (absolute CD4 count, absolute CD8 count) 120 days after ASCT | 120 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To report the 3-year progression-free survival for both treatment arms - intensified vs. therapeutic Vitamin D supplementation |  | 3 years | 
| To report the overall response rate for both treatment arms 120 days after ASCT for adult patients with multiple myeloma. |  | 120 Days | 
| To report the overall response rate for both treatment arms 2 years after transplantation |  | Two Years | 
| To report the 3-year overall survival for the two treatment arms after transplantation. |  | Three Years | 
| To report the minimal residual disease status for the two treatment arms at randomization, and within 120 days after transplantation and 2 years after transplantation. |  | Randomization; 120 days after transplantation; two years after transplantation. | 
| To report the vitamin D levels between the two treatments arms before autologous stem cell transplant, within 120 days, and 3-years post-transplantation |  | Before autologous stem cell transplant; 120 days after transplantation; three years post-transplantation | 
| To describe the adverse events for the two treatment arms |  | Three years | 
| To report time to neutrophil and platelet engraftment as well as transfusion independence after transplantation in both treatment arms |  | After transplantation, an average of 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myeloma, Multiple, Vitamin D, Vitamins, Lenalidomide, Revlimid, Cholecalciferol, Transplantation, Autologous, Vitamin D Deficiency