Lenalidomide Plus Melphalan as a Preparative Regimen for Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma: A Phase 1 / 2 Study

NCT01054196 | Active Not Recruiting Phase 1 Results FDA Drug

• 1 other identifier: 0909010623
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Lenalidomide That Can be Added to Melphalan

  The primary endpoint for the phase 1 portion of this study is to determine the maximum tolerated dose of lenalidomide that can be added to melphalan.

  12 months

• Duration of Overall Response (DoR)

  The primary endpoint for the phase 2 portion of this study is to determine the duration of overall response (DoR). The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

  Until disease progression, death, or for a maximum of 3 years, whichever occurs first

Secondary Outcomes (3)

• Overall Response Rate

  Until disease progression or a maximum of 3 years, whichever occurs first

• Overall Survival

  Until death or date of last contact with the subject

• Mean Functional Assessment of of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Score

  Cycle 6, day 1, at approximately 4.5 months

Study Arms (7)

Phase 1 Dose level 1

EXPERIMENTAL

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).

Drug: lenalidomide; Drug: melphalan

Phase 1 Dose level 2

EXPERIMENTAL

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).

Drug: lenalidomide; Drug: melphalan

Phase 1 Dose level 3

EXPERIMENTAL

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).

Drug: lenalidomide; Drug: melphalan

Phase 1 Dose level 4

EXPERIMENTAL

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).

Drug: lenalidomide; Drug: melphalan

Phase 1 Dose level 5

EXPERIMENTAL

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).

Drug: lenalidomide; Drug: melphalan

Phase 1 Dose level 6

EXPERIMENTAL

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).

Drug: lenalidomide; Drug: melphalan

Phase 2 Expansion

EXPERIMENTAL

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

Drug: lenalidomide; Drug: melphalan

Interventions

lenalidomide DRUG

daily dose dependent on dose-escalation schedule

Also known as: Revlimid

Phase 1 Dose level 1; Phase 1 Dose level 2; Phase 1 Dose level 3; Phase 1 Dose level 4; Phase 1 Dose level 5; Phase 1 Dose level 6; Phase 2 Expansion

melphalan DRUG

100 mg/m2 given Days -2 and -1

Phase 1 Dose level 1; Phase 1 Dose level 2; Phase 1 Dose level 3; Phase 1 Dose level 4; Phase 1 Dose level 5; Phase 1 Dose level 6; Phase 2 Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed relapsed, primary refractory, or relapsed and refractory multiple myeloma.
• Patients must have measurable disease as defined by the International Uniform Response Criteria,defined as any of the following:
• serum M-protein of \> = 500mg/dL
• urine M-protein of \> = 200mg/ 24 hours
• involved free light chain \> = 10mg/dL provided serum free light chain ratio is abnormal
• Patients must have received at least one prior line of therapy.
• Age \> = 18 years.
• Life expectancy of greater than 12 weeks.
• ECOG performance status \< = 2.
• All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist.
• Patients must have normal organ and marrow function as defined below:
• ANC \> = 1,000/uL
• platelets \> = 50,000/uL
• total bilirubin \< = 1.5 X upper limit of normal
• AST(SGOT)/ALT(SGPT) \< = 2.5 X upper limit of normal

You may not qualify if:

• Patients who have had myeloma therapy within 14 days prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier. Patients may have received bisphosphonate therapy as part of routine myeloma care at any time prior to study entry.
• 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.
• Known positive for HIV or infectious hepatitis, type B or C.
• Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.
• History of thrombosis or thromboembolic event within last 60 days prior to study entry.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Celgene: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Roger Pearse, M.D. PhD
• Organization: Weill Cornell Medicine

rnp2001@med.cornell.edu

646-962-6500

Study Officials

• Roger Pearse, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2010
• First Posted: January 22, 2010
• Study Start: August 1, 2010
• Primary Completion: October 1, 2021
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 8, 2026
• Results First Posted: May 13, 2025

Record last verified: 2026-03

Locations

US (1)