Lenalidomide-Dexamethasone-DLI for Multiple Myeloma

Not currently recruiting at 1 trial location

Overseen By Nathalie Lachapelle, B.Sc. INF

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ciusss de L'Est de l'Île de Montréal

Must be taking: Lenalidomide, Dexamethasone

Disqualifiers: Acute GVHD, Chronic GVHD, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks better methods to control multiple myeloma (a type of blood cancer) after it returns following a bone marrow transplant. It tests a combination of two drugs, Lenalidomide and Dexamethasone (a corticosteroid), to create an environment where donor immune cells can fight the cancer more effectively. The goal is to improve survival and slow disease progression. This trial suits those who have relapsed multiple myeloma after a sibling or unrelated donor bone marrow transplant and currently have measurable disease. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific situation with the trial investigators.

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

Research shows that using lenalidomide, dexamethasone, and donor lymphocyte infusions (DLIs) is generally safe for patients with relapsed multiple myeloma. Previous studies found this treatment both feasible and safe for these patients. Patients who used this combination after a stem cell transplant did not encounter major problems.

However, like any treatment, side effects can occur. For instance, if severe side effects arise with lenalidomide, doctors can adjust the dose to enhance safety. This means that if patients experience harmful effects, the dose can be lowered.

Overall, past studies suggest that this treatment approach is reasonable and can be tolerated by patients. Since individual reactions can vary, patients should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Lenalidomide-Dexamethasone-DLI treatment for multiple myeloma because it combines three powerful approaches: medication and targeted immune cell infusions. While standard treatments like chemotherapy and stem cell transplants focus on eliminating cancer cells, this regimen also involves donor lymphocyte infusions (DLIs) to boost the patient's immune response. By adjusting the dose of Lenalidomide based on the presence of graft-versus-host disease (GVHD), the treatment aims to maximize its effectiveness while minimizing side effects. This unique combination offers potential for enhanced control of the disease and may improve long-term outcomes for patients.

What evidence suggests that this treatment might be an effective treatment for multiple myeloma?

Research has shown that using lenalidomide with dexamethasone is promising for treating multiple myeloma, a type of blood cancer. Studies have found that about 50% of patients respond well to this treatment, experiencing better disease control. In one study, 31 out of 34 patients had positive results, with some showing no detectable cancer after treatment. Lenalidomide boosts the immune system and may also inhibit blood vessels from feeding the tumor, slowing its growth. This trial will evaluate the combination of lenalidomide, dexamethasone, and donor lymphocyte infusions (DLI) to determine if it can help patients live longer without disease progression and improve overall survival. ^{6 7 8 9 10}

Who Is on the Research Team?

Jean Roy, MD

Principal Investigator

Ciusss de L'Est de l'Île de Montréal

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with multiple myeloma in first relapse post-allogeneic stem cell transplant. Participants must not be pregnant, planning pregnancy, or breastfeeding and must follow strict contraception guidelines. They should have measurable disease but no recent participation in other drug trials, no early post-transplant relapse, no Lenalidomide resistance or active severe infections.

Inclusion Criteria

My myeloma has returned after my first stem cell transplant.

You have a detectable disease based on specific criteria at the time of a relapse.

All study participants must comply with the Revlimid Pregnancy Prevention Plan

Exclusion Criteria

Your bilirubin, AST and ALT levels are too high, unless it's due to a condition called Gilbert's disease or hemolysis. Your alkaline phosphatase level is also too high.

I do not have an active infection with HIV, HTLV-1 or 2, hepatitis B, or hepatitis C.

You are currently struggling with drug or alcohol abuse.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lenalidomide and Dexamethasone daily for 21 days with Dexamethasone 40 mg once weekly for 6 cycles of 28 days each

24 weeks

6 visits (in-person) for each cycle

Donor Lymphocyte Infusions (DLIs)

Participants receive 3 donor lymphocyte infusions at specified doses

3 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including bone marrow aspirates and PET scans

5 years

Every 3 months for 1 year, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• DLI
• Lenalidomide

Trial Overview

The study tests a two-step treatment combining Lenalidomide (Len) and Dexamethasone (Dex), followed by Donor Leukocytes Infusions (DLIs). This aims to control the disease after relapse from stem cell transplant by creating an environment that allows DLIs to work better while reducing the risk of graft-versus-host disease.

How Is the Trial Designed?

Group I: Lenalidomide-Dexamethasone-DLI Experimental Treatment 1 Intervention

1. Patients will receive Len (10 mg in the presence of ≤ grade I acute GVHD or absence of chronic GVHD; 5 mg in presence of controlled mild or moderate chronic GVHD) daily x 21 days with Dex 40 mg once weekly for a total of 6 cycles of 28 days each 1. For grade ≥III non hematologic or grade IV hematologic toxicity, Len can be reduced to 5 mg 2. In absence of these toxicities, acute GVHD (using Glucksberg modified criteria) or severe chronic GVHD (using NIH criteria), Len dose can be increased by 5 mg per cycle to a maximum of 25 mg 2. If eligibility is confirmed, sibling and unrelated donor transplant recipients will both receive 3 donor lymphocyte infusions (DLIs) at the following doses: 5 x 106 CD3+/kg; 1 x 107 CD3+/kg; 5 x 107 CD3+/kg 3. Patient will be followed for 5 years post relapse.

Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

Ciusss de L'Est de l'Île de Montréal

Lead Sponsor

Trials

81

Recruited

6,400+

C3i Center Inc.

Collaborator

Trials

1

Recruited

10+

Celgene

Industry Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

In a large observational study of 2150 patients with relapsed/refractory multiple myeloma, lenalidomide plus dexamethasone demonstrated a favorable safety profile, with lower incidence rates of neuropathy and infections compared to other treatments like bortezomib and thalidomide.

The study confirmed that lenalidomide's safety profile in a real-world setting is consistent with previous clinical trial data, with no new safety concerns identified, although it did show a higher incidence of neutropenia compared to bortezomib and thalidomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. Gamberi, B., Berthou, C., Hernandez, M., et al.[2021]

Lenalidomide, when combined with dexamethasone, significantly improves response rates and survival in patients with relapsed/refractory multiple myeloma, showing a response rate of 60% compared to 20% with placebo in Phase III trials.

While lenalidomide is effective, it is associated with common adverse events such as hematologic toxicity and venous thromboembolism, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatment strategies with lenalidomide in multiple myeloma and future perspectives. Larocca, A., Cavallo, F., Mina, R., et al.[2018]

In a phase 2 trial and extended access program involving Chinese patients with relapsed/refractory multiple myeloma, lenalidomide plus low-dose dexamethasone (Rd) demonstrated a manageable safety profile, with 60% of patients experiencing Grade 3-4 adverse events, but no patients discontinued treatment due to these adverse effects.

Rd provided sustained efficacy, with a median duration of response of 35.1 months, median time to progression of 36.9 months, and median progression-free survival of 36.0 months, indicating that long-term treatment can be effective for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term use of lenalidomide and low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: MM-024 Extended Access Program. Du, X., Jin, J., Cai, Z., et al.[2018]

Lenalidomide, when combined with dexamethasone, has shown superior efficacy in treating relapsed multiple myeloma compared to dexamethasone alone, as demonstrated in two large phase III studies that reported improved response rates, progression-free survival, and overall survival.

The drug is administered orally in a 21-day cycle and has manageable side effects, such as neutropenia and venous thrombotic events, making it a viable treatment option for patients who have undergone at least one prior therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

United Kingdom myeloma forum position statement on the use of lenalidomide in multiple myeloma. Davies, F., Morris, C., Bird, J., et al.[2018]

Lenalidomide combined with dexamethasone has been shown to be effective for treating relapsed/refractory multiple myeloma, and it has received approval from both the FDA and EMA for patients who have undergone at least one prior therapy.

The most common serious side effects include cytopenias and infections, but an expert panel has provided management strategies to minimize these risks, ensuring that patients can receive the full benefits of the treatment without unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Palumbo, A., Dimopoulos, M., San Miguel, J., et al.[2018]

Lenalidomide, in combination with dexamethasone, was administered to 1438 patients with relapsed or refractory multiple myeloma, showing a median treatment duration of 15.4 weeks and confirming its efficacy in this patient population.

The most common adverse events included hematological issues (49%), gastrointestinal problems (59%), and fatigue (55%), with serious adverse events like pneumonia occurring in 8% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded safety experience with lenalidomide plus dexamethasone in relapsed or refractory multiple myeloma. Chen, C., Reece, DE., Siegel, D., et al.[2021]

In a study involving 792 patients with relapsed multiple myeloma, the combination of carfilzomib with lenalidomide and dexamethasone significantly improved progression-free survival, with a median of 26.3 months compared to 17.6 months for the control group.

The carfilzomib group also showed a higher overall response rate (87.1% vs. 66.7%) and better health-related quality of life, indicating a favorable risk-benefit profile despite similar rates of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. Stewart, AK., Rajkumar, SV., Dimopoulos, MA., et al.[2022]

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]

In a study involving 98 relapsed refractory multiple myeloma patients, treatment with lenalidomide plus dexamethasone resulted in a 52% overall response rate, with 49% achieving partial remission and 3% achieving complete remission, despite patients having undergone a median of 5 prior treatments.

The combination therapy not only provided rapid responses but also extended overall survival by nearly six months, demonstrating its efficacy and safety regardless of previous treatments with thalidomide and bortezomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. Delforge, M., Michiels, A., Doyen, C., et al.[2018]

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