Lenalidomide + Melphalan for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Weill Medical College of Cornell University

Must be taking: Lenalidomide, Low-dose aspirin

Must not be taking: Investigational agents

Disqualifiers: HIV, Hepatitis B/C, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: Unknown

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a potential new treatment combination for people with relapsed multiple myeloma, a type of blood cancer. The goal is to determine the safest dose of lenalidomide (a drug that modifies the body’s immune response) when combined with melphalan (a chemotherapy drug) before a stem cell transplant. Participants will help researchers assess whether this combination improves response rates and how long the benefits last. Individuals whose multiple myeloma has returned or not responded to initial treatments, and who have tried at least one prior therapy, might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

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

Research has shown that lenalidomide and melphalan are often used together to treat multiple myeloma. Studies have found this combination effective, but it may also cause side effects. Lenalidomide is generally well-tolerated but can lead to low blood counts, tiredness, or skin rashes. Melphalan, a chemotherapy drug, effectively kills myeloma cells, especially before stem cell transplants, but it can also cause nausea, vomiting, and hair loss.

Earlier research identified myelosuppression (a decrease in bone marrow activity) as a main side effect of lenalidomide, limiting the safe dosage. Trials noted no major side effects at certain dose levels, suggesting they were manageable.

Both drugs are regularly used for multiple myeloma, with well-documented safety profiles. This trial is in the early stages, focusing on safety and determining the right dose. Prospective participants should discuss potential side effects and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of lenalidomide and melphalan for treating multiple myeloma because it offers a potent, multi-faceted approach. Unlike standard treatments, which often rely on a single mechanism, this combination utilizes lenalidomide to enhance the immune system's response and melphalan to directly target cancer cells, potentially leading to more effective outcomes. Additionally, this regimen is unique because it involves a high-dose lenalidomide protocol that gradually escalates, potentially improving patient tolerance and minimizing side effects. By combining these strategies, researchers hope to achieve better remission rates and improve overall survival for multiple myeloma patients.

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

Research has shown that using lenalidomide with melphalan might improve treatment outcomes for multiple myeloma, a type of blood cancer. This trial will explore various dose levels of lenalidomide combined with melphalan to determine the most effective regimen. Studies have found that adding lenalidomide to standard treatments can increase the chances of a positive response. This combination is believed to be more effective than melphalan alone. Additionally, lenalidomide can help maintain long periods without disease progression, even if the dose is reduced over time. These findings suggest that the lenalidomide and melphalan combination could be a promising option for those whose multiple myeloma has returned. ^{1 2 3 4 6}

Who Is on the Research Team?

Roger Pearse, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed multiple myeloma who've had at least one prior treatment. They must have measurable disease, adequate organ/marrow function, and a good performance status. Participants need to agree to birth control measures and anticoagulation therapy. Exclusions include recent myeloma therapy, HIV/hepatitis infection, uncontrolled illnesses, pregnancy/lactation, history of thrombosis or allergies to the drugs tested.

Inclusion Criteria

All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist

My organ and bone marrow functions are normal.

I have enough CD34+ stem cells collected for a transplant.

Exclusion Criteria

I have not had a blood clot in the last 60 days.

Patients may not be receiving any other investigational agents

History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide (including thalidomide) or melphalan

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Dose escalation of lenalidomide to determine the maximal tolerated dose prior to autologous stem cell transplantation

5 days

Daily visits for dose administration

Phase 2 Treatment

Administration of high-dose lenalidomide and melphalan followed by autologous stem cell transplantation

5 days for lenalidomide, 2 days for melphalan, followed by stem cell infusion

Daily visits for drug administration and stem cell infusion

Maintenance

Maintenance lenalidomide begins at Day +100 with 28-day cycles

Until disease progression or a maximum of 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years or until disease progression

What Are the Treatments Tested in This Trial?

Interventions

• Lenalidomide
• Melphalan

Trial Overview The study aims to find the highest safe dose of lenalidomide combined with high-dose melphalan before stem cell transplantation in Phase 1. In Phase 2, it tests if this combination followed by maintenance lenalidomide can improve response rates and duration in relapsed multiple myeloma patients.

How Is the Trial Designed?

Group I: Phase 2 Expansion Experimental Treatment 2 Interventions

Early studies noted a dose response relationship and found myelosuppression to be the dose limiting toxicity. In this Phase 1 study of high dose lenalidomide (HDLEN) with HDM in conditioning for ASCT shown no DLT noted up to 350mg PO daily of LEN. In Phase 2, HDLEN was dosed at 350mg PO daily from day -5 to day -1 and HDM was dosed 100mg/m2 on days -2 and -1. After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles). lenalidomide: daily dose dependent on dose-escalation schedule melphalan: 100 mg/m2 given Days -2 and -1

Group II: Phase 1 Dose level 6 Experimental Treatment 2 Interventions

Oral lenalidomide 150mg qAM, 200mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles).

Group III: Phase 1 Dose level 5 Experimental Treatment 2 Interventions

Oral lenalidomide 100mg qAM, 150mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles).

Group IV: Phase 1 Dose level 4 Experimental Treatment 2 Interventions

Oral lenalidomide 75mg qAM, 100mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles).

Group V: Phase 1 Dose level 3 Experimental Treatment 2 Interventions

Oral lenalidomide 50mg qAM, 75mg qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles).

Group VI: Phase 1 Dose level 2 Experimental Treatment 2 Interventions

Oral lenalidomide 25mg qAM, 50mq qPM x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles).

Group VII: Phase 1 Dose level 1 Experimental Treatment 2 Interventions

Oral lenalidomide 25mg twice daily x 5 days (designated as days -5 to -1). On days-2 and -1, all patients will receive 100mg/m2 of intravenous melphalan once daily for a total of 2 doses (200mg/m2total). After a period of 24-72 hours has elapsed from the last melphalan dose (designated as Day 0) each patient will receive infusion of at least 2.0 x 106/kg of autologous CD34+ stem cells. Maintenance lenalidomide will begin at Day +100 at a dose of 25 mg/day, orally for 1-21 days followed by a 7-day rest period (28 day cycles).

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?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

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

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8123041/

Treatment of Multiple Myeloma and the Role of Melphalan in ... Therapy based on 211At-OKT10-B10 in combination with melphalan before a stem cell transplant may be more effective than melphalan monotherapy in MM. NCT03556332 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00843310

Combination of Revlimid, Melphalan and Dexamethasone ... This study is to determine whether addition of Revlimid to standard therapy will increase overall and complete response rates compared to historical ...

3. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2006-001865-41/AT

Clinical Trials Register A clinical study to compare the effectiveness and safety of the combination of lenalidomide, melphalan and prednisone with placebo, melphalan ...

4. myeloma.org myeloma.org/revlimid-lenalidomide

Revlimid (Lenalidomide) Results from clinical trials show that with dose reductions after 12 months or longer of Revlimid therapy, treatment benefit is retained. Long remissions ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT01079936/lenalidomide-and-high-dose-melphalan

Lenalidomide and High-Dose Melphalan The goal of this clinical research study is to find the highest tolerable dose of the combination of Revlimid (lenalidomide) and high-dose ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00112827

Study Details | NCT00112827 | Melphalan and Radiation ... RATIONALE: Melphalan, a chemotherapeutic agent, has been found to be an effective treatment choice for destroying myeloma cells, especially when given at ...