Vitamin D + Lenalidomide for Multiple Myeloma

Overseen By GCC Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Amany Keruakous, MD, MS.

Must be taking: Lenalidomide

Must not be taking: Investigational agents

Disqualifiers: Amyloidosis, Progressive disease, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 120

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding Vitamin D to the cancer drug lenalidomide (Revlimid) can help people with multiple myeloma, a type of blood cancer, live longer without disease progression. After a stem cell transplant, one group will receive both Vitamin D and lenalidomide, while the other will receive only lenalidomide. The main goal is to determine if Vitamin D aids immune recovery and extends the time patients remain free from cancer progression. People who have had multiple myeloma requiring treatment before a stem cell transplant might be suitable for this trial. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering a unique opportunity to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must be able to take and swallow oral medication and comply with certain requirements related to lenalidomide. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study linked lenalidomide to some side effects. About 23% of patients experienced a loss of appetite, while only 3% faced issues with weight loss or malnutrition. Another study showed that lenalidomide, combined with dexamethasone (a type of steroid), improved response rates and survival for patients with multiple myeloma. This suggests lenalidomide is generally well-tolerated, though some side effects can occur.

Research has shown that vitamin D is important for patients with multiple myeloma. Many of these patients have low vitamin D levels, which can lead to worse health outcomes. High doses of vitamin D effectively increase levels in patients. However, specific data on side effects from vitamin D supplements in this context is limited.

Overall, lenalidomide has a strong safety record for treating multiple myeloma, and vitamin D is generally safe, especially when used to correct deficiencies. Patients should always consult a healthcare provider about any concerns with side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for multiple myeloma because it combines Vitamin D with lenalidomide, which is already a standard therapy for this condition. Unlike traditional approaches that focus solely on lenalidomide, adding Vitamin D might enhance the body's immune response and improve patient outcomes. The unique aspect of this approach is its potential to optimize overall response rates and reduce measurable residual disease by leveraging the immune-modulating effects of Vitamin D alongside lenalidomide's proven efficacy. This combination could offer a more comprehensive strategy to manage multiple myeloma effectively.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research suggests that Vitamin D might benefit people with multiple myeloma, a type of blood cancer. Studies have shown that higher doses of Vitamin D can significantly raise vitamin levels in patients, potentially linking to better health outcomes. Many people with multiple myeloma have low Vitamin D levels, which correlate with poorer health results. In this trial, one group of participants will receive maintenance Vitamin D before autologous transplantation (ASCT), while another group will not.

Lenalidomide is another treatment proven to help multiple myeloma patients. Research shows that it can improve overall survival when used continuously over several treatment cycles. Patients often respond well to lenalidomide, making it an important part of multiple myeloma treatment plans. In this trial, all participants will receive lenalidomide, with or without maintenance Vitamin D. ^{1 2 6 7 8}

Who Is on the Research Team?

Amany Keruakous, MD

Principal Investigator

Georgia Cancer Center at Augusta University

Are You a Good Fit for This Trial?

This trial is for adults with multiple myeloma who can take blood clot prevention meds and comply with specific program requirements. They must be eligible for or have completed a stem cell transplant within the last 120 days, able to swallow pills, and not have other cancers or known allergies to Vitamin D supplements.

Inclusion Criteria

I have been diagnosed with multiple myeloma and do not have amyloidosis.

I can swallow pills without any issues.

I am willing to take blood clot prevention medication and follow the lenalidomide program.

Exclusion Criteria

I have been diagnosed with another type of cancer before.

I have had a previous organ or stem cell transplant.

I am allergic to the study drug (Vitamin D3).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Transplantation

Participants receive maintenance Vitamin D3 or no maintenance Vitamin D prior to autologous stem cell transplantation (ASCT)

Up to 120 days

Regular visits for assessment

Post-Transplantation Treatment

Participants receive lenalidomide with or without maintenance Vitamin D post-ASCT

3 years

Regular follow-up visits

Follow-up

Participants are monitored for safety, overall response rate, progression-free survival, and overall survival

3 years

Periodic assessments at 120 days, 2 years, and 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Lenalidomide
• Vitamin D - Intensified
• Vitamin D - Therapeutic

Trial Overview The study compares two groups: one taking lenalidomide with high-dose Vitamin D (intensified regimen) and another taking lenalidomide with standard-dose Vitamin D (therapeutic regimen). It aims to see how these affect immune recovery post-transplant and survival without disease progression over three years.

How Is the Trial Designed?

Group I: Maintenance Vitamin D Experimental Treatment 2 Interventions

In this arm, patients will receive maintenance Vitamin D3 prior to autologous transplantation (ASCT). Within 120 days after ASCT the following will be assessed: vitamin D level, Overall Response Rate (ORR) and Measurable Residual Disease (MRD). Then patients will receive lenalidomide and continuation of maintenance Vitamin D.

Group II: No Maintenance Vitamin D Active Control 2 Interventions

In this arm, patients will receive no maintenance vitamin D prior to ASCT. Within 120 days after ASCT the following will be assessed: vitamin D level, ORR, and MRD. Then patients will receive the standard lenalidomide dose along with no maintenance vitamin D.

Lenalidomide is already approved in European Union, United States for the following indications:

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Who Is Running the Clinical Trial?

Amany Keruakous, MD, MS.

Lead Sponsor

Trials

1

Recruited

100+

Published Research Related to This Trial

Lenalidomide maintenance therapy significantly prolongs progression-free survival (PFS) in patients with newly diagnosed multiple myeloma after autologous stem-cell transplantation, as shown in pivotal phase 3 trials like IFM 2005-02 and CALGB 100104.

While lenalidomide is associated with some increased risks, such as grade 3/4 adverse events and a higher chance of second primary cancers, the overall survival benefits outweigh these risks, making it a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: A Review in Newly Diagnosed Multiple Myeloma as Maintenance Therapy After ASCT. Syed, YY.[2018]

Lenalidomide significantly improves progression-free survival (PFS) in patients with newly diagnosed multiple myeloma not eligible for stem-cell transplantation, as shown in randomized trials like the FIRST and MM-015 trials.

Continuous lenalidomide therapy is associated with less toxicity compared to thalidomide, maintaining tolerability without increasing the risk of neutropenia or second primary malignancies, making it a safer long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: a review of its continuous use in patients with newly diagnosed multiple myeloma not eligible for stem-cell transplantation. McCormack, PL.[2018]

Lenalidomide, when combined with dexamethasone, significantly improves time to progression in patients with multiple myeloma compared to placebo, as shown in two randomized, double-blind studies.

However, the treatment is associated with serious side effects, including increased risks of neutropenia, thrombocytopenia, and thromboembolic events, leading to its restricted distribution under the RevAssist program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of multiple myeloma after one prior therapy. Hazarika, M., Rock, E., Williams, G., et al.[2020]

Lenalidomide is an effective treatment for patients with relapsed or refractory multiple myeloma, showing promising clinical activity and is approved by the FDA.

Common side effects of lenalidomide include neutropenia, thrombocytopenia, and thromboembolic events, necessitating careful monitoring to prevent serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: a new agent for patients with relapsed or refractory multiple myeloma. Tariman, JD.[2018]

Lenalidomide is a powerful treatment for multiple myeloma (MM) that works by directly causing cancer cell death, preventing cancer cells from sticking to bone marrow, and enhancing the body's immune response against tumors.

In combination with dexamethasone, lenalidomide has shown superior effectiveness in clinical trials, leading to improved patient outcomes such as longer survival and FDA approval for treating relapsed MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of lenalidomide in combination with dexamethasone for the treatment of multiple myeloma. Hideshima, T., Raje, N., Richardson, PG., et al.[2021]

Lenalidomide is a more potent and less toxic alternative to thalidomide, showing significant efficacy in treating relapsed or refractory multiple myeloma, both as a single agent and in combination with other treatments.

While lenalidomide leads to high response rates and improved survival in multiple myeloma patients, it carries a risk of thromboembolism, particularly when used with steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of plasma cell dyscrasias with lenalidomide. Dimopoulos, MA., Kastritis, E., Rajkumar, SV.[2018]

Lenalidomide has become a crucial treatment option for multiple myeloma and del-5q myelodysplastic syndromes, and it has been tested for various other cancers, showcasing its broad therapeutic potential.

The drug received FDA approval for use in combination with dexamethasone for previously treated multiple myeloma, highlighting its efficacy and safety in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: a novel anticancer drug with multiple modalities. Galustian, C., Dalgleish, A.[2019]

Lenalidomide (Revlimid) has been rapidly developed and recently approved for treating relapsed multiple myeloma, showing durable clinical responses, especially when combined with dexamethasone.

Clinical trials indicate that lenalidomide is generally well tolerated by patients, with manageable side effects, making it a promising option for those with relapsed and refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in multiple myeloma. Richardson, PG., Mitsiades, C., Hideshima, T., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9972020/

Real‐world data on lenalidomide dosing and outcomes in ... The objective of our study was to understand the dosing, efficacy, and tolerability of lenalidomide among TI NDMM patients in the real‐world setting.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924017647

Characteristics and outcomes in patients with lenalidomide ... Outcomes were suboptimal: 55 % response rate, 10-mo median PFS, and 28-mo median OS. •. New, effective therapies are needed for this difficult-to-treat ...

3. esmoopen.com esmoopen.com/article/S2059-7029(25)01383-3/fulltext

A network meta-analysis of randomized clinical trials in ... Comparative efficacy of lenalidomide-free regimens in patients with relapsed/refractory multiple myeloma (RRMM) previously exposed to ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5774211/

Final analysis of survival outcomes in the phase 3 FIRST ... Key Points. Rd continuous significantly extended OS compared with MPT and resulted in comparable OS to that with Rd18 in patients with multiple myeloma.

5. bloodcancerstoday.com bloodcancerstoday.com/post/clinical-study-finds-continuous-lenalidomide-delivery-effective-and-well-tolerated-in-rrmm

Clinical Study Finds Continuous Lenalidomide Delivery ... Administration of lenalidomide continuously for six or more cycles shows meaningful efficacy in patients with relapsed or refractory multiple myeloma (RRMM) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3256976/

Safety and Efficacy of Lenalidomide in Relapsed or ... Combination lenalidomide and dexamethasone (Len+Dex) has been shown to increase response rates and prolong survival compared with dexamethasone alone.

7. myeloma.org myeloma.org/revlimid-lenalidomide

Revlimid (Lenalidomide) In the phase III FIRST clinical trial, 23% of the newly diagnosed patients experienced a decreased appetite. Of those, only 3% had weight loss or malnutrition.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2152265022017529

Generic Lenalidomide Rivelime Versus Brand-name ... This study aimed to compare use of original brand-name lenalidomide (Revlimid®) vs. generic equivalent (Rivelime®) in terms of efficacy, safety and survival ...