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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: lenalidomide; Drug: melphalan

Detailed Description

Experimental: Phase 1 Subjects will dose escalate lenalidomide in a series of subjects in a 3+3 design through 6 dose levels of lenalidomide (as per modified Fibonacci escalation) to determine the maximal tolerated dose (MTD)of lenalidomide prior to ASCT.

Planned dose levels of lenalidomide in Phase 1 portion of study:

Dose Level/ Lenalidomide Dose / Schedule

-1: 25mg daily x 5 days

1. 25mg twice daily x 5 days
2. 25mg qAM, 50mq qPM x 5 days
3. 50mg qAM, 75mg qPM x 5 days
4. 75mg qAM, 100mg qPM x 5 days
5. 100mg qAM, 150mg qPM x 5 days
6. 150mg qAM, 200mg qPM x 5 days

Experimental: Phase 2 The MTD determine for lenalidomide in the phase 1 portion of this study will be used in the transplant phase of the phase 2 portion.

In the transplant phase of the study, all participants will receive oral lenalidomide at the pre-determined dose level for phase 1 and MTD for phase 2 for 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).

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
  • Cardiac Ejection Fraction > = 45 %
  • Creatinine clearance > 60 cc/min
• Patients must have an adequate number of CD34+ stem cells collected to allow for transplantation. This number is defined as ≥ 2 x 106 CD34+ cells / kg body weight. If not previously collected and stored, the patient must be willing to undergo stem cell mobilization and collection as per standard practice.
• The effects of lenalidomide on the developing human fetus at the recommended therapeutic dose are unknown; however, it has been shown to be teratogenic other primates. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. The treating physician will follow the adverse reporting guidelines as outlined in further detail below for pregnancies.
• Lenalidomide has been shown to carry a risk of thromboembolic events, especially when used in combination with either corticosteroids or alkylating chemotherapeutic agents. All patients who participate in this study must be willing and able to tolerate prophylactic anticoagulation with low-molecular weight heparin (LMWH) for the required dates in treatment protocol. Patients also must be able to tolerate low-dose aspirin, 81 mg daily, during the maintenance phase of the treatment protocol.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Dose level 1; 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; daily dose dependent on dose-escalation schedule; Other Names: Revlimid; Drug: melphalan; 100 mg/m2 given Days -2 and -1
Experimental: Phase 1 Dose level 2; 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; daily dose dependent on dose-escalation schedule; Other Names: Revlimid; Drug: melphalan; 100 mg/m2 given Days -2 and -1
Experimental: Phase 1 Dose level 3; 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; daily dose dependent on dose-escalation schedule; Other Names: Revlimid; Drug: melphalan; 100 mg/m2 given Days -2 and -1
Experimental: Phase 1 Dose level 4; 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; daily dose dependent on dose-escalation schedule; Other Names: Revlimid; Drug: melphalan; 100 mg/m2 given Days -2 and -1
Experimental: Phase 1 Dose level 5; 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; daily dose dependent on dose-escalation schedule; Other Names: Revlimid; Drug: melphalan; 100 mg/m2 given Days -2 and -1
Experimental: Phase 1 Dose level 6; 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; daily dose dependent on dose-escalation schedule; Other Names: Revlimid; Drug: melphalan; 100 mg/m2 given Days -2 and -1
Experimental: Phase 2 Expansion; 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; daily dose dependent on dose-escalation schedule; Other Names: Revlimid; Drug: melphalan; 100 mg/m2 given Days -2 and -1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Overall response rate is the number of patients with complete response and partial response. Response is defined by the International Uniform Response Criteria for Multiple Myeloma (IURC)	Until disease progression or a maximum of 3 years, whichever occurs first
Overall Survival	Overall survival is defined as the interval between the day of transplantation (Day 0) and date of death. If the date of death is uncertain, the date of last contact with the subject will be used.	Until death or date of last contact with the subject
Mean Functional Assessment of of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Score	quality of life will be evaluated and scored using the questionnaire from the bone marrow transplant subscale of the Functional Assessment of Cancer Therapy available from w ww.facit.org. The FACT-BMT is a 50 item questionnaire that measures five dimensions of quality of life in bone marrow transplant patients, including physical well-being, social and family well-being, emotional well-being, functional well-being, and additional concerns. It is scored on a 5 point Likert scale. Total scores range from 0 to 148, with a higher score indicating higher quality of life.	Cycle 6, day 1, at approximately 4.5 months

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Celgene
• Investigators: Principal Investigator: Roger Pearse, MD, Weill Medical College of Cornell University

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2010
• Primary Completion (Actual): October 1, 2021
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 19, 2010
• First Submitted That Met QC Criteria: January 19, 2010
• First Posted (Estimated): January 22, 2010

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Carboxylic Acids; Piperidines; Amino Acids; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Melphalan
• Other Study ID Numbers: 0909010623

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No