Lenalidomide + Melphalan for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Weill Medical College of Cornell University

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

Compensation: Varies

Number of Visits: Unknown

52 Participants Needed

Trial Summary

What is the purpose of this trial?

A) Phase 1: To determine the maximal tolerated dose (MTD) of lenalidomide that can be safely added to high-dose melphalan prior to autologous stem cell transplantation (ASCT). B) Phase 2: To determine whether the addition of high-dose lenalidomide to ASCT followed by maintenance standard-dose lenalidomide improves the response rate and duration of response for relapsed multiple myeloma (RMM).

Research Team

Roger Pearse, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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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