Melphalan, Prednisone, and Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma

This study is ongoing, but not recruiting participants.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic Identifier:
First received: May 23, 2007
Last updated: October 1, 2015
Last verified: October 2015

RATIONALE: Drugs used in chemotherapy, such as melphalan, prednisone, and lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of melphalan and lenalidomide when given together with prednisone and to see how well they work in treating patients with newly diagnosed multiple myeloma.

Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: lenalidomide
Drug: melphalan
Drug: prednisone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Melphalan, Prednisone Plus Lenalidomide in Patients With Newly Diagnosed Multiple Myeloma Who Are Not Candidates for Stem Cell Transplant

Resource links provided by NLM:

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Patients With Overall Confirmed Response [ Time Frame: Every cycle during treatment ] [ Designated as safety issue: No ]

    Response that was confirmed on 2 consecutive evaluations.

    • Complete Response (CR): Complete disappearance of M-protein from serum and urine on immunofixations, normalization of Free Light Chain (FLC) ratio and <=5% plasma cells in bone marrow
    • Very Good Partial Response (VGPR): >=90% reduction in serum M-spike, Urine M-spike <100mg per 24 hours
    • Partial Response (PR): >=50% reduction in serum M-spike, Urine M-spike >=90% reduction or < 200mg per 24 hours, or >=50% decrease in difference between involved and uninvolved FLC levels or 50% decrease in bone marrow plasma cells

Secondary Outcome Measures:
  • Time to Progression (TTP) [ Time Frame: registration to progressive disease (up to 3 years) ] [ Designated as safety issue: No ]
    TTP was defined as the time from registration to disease progression. Patients who died were considered to have disease progression at time of death unless documented evidence clearly indicates no progression has occurred

  • Overall Survival (OS) [ Time Frame: registration to death (up to 3 years) ] [ Designated as safety issue: No ]
    OS was defined as the time from registration to death due to any cause. Patients who were alive were censored at date of last follow-up.

  • Duration of Response (DOR) [ Time Frame: from first response to progression or death (up to 3 years) ] [ Designated as safety issue: No ]
    Duration of response was calculated from documentation of first response to date of progression in the subset of patients who responded. Patients without progression were censored at the date of last tumor evaluation.

  • Patients With Grade 3 or Higher Adverse Events [ Time Frame: Every cycle during treatment ] [ Designated as safety issue: Yes ]
    Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0.

Enrollment: 33
Study Start Date: June 2005
Estimated Study Completion Date: December 2016
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (Lenalidomide, Melphalan, Prednisone)

Intervention: Drug: lenalidomide Dose determined by Phase I treatment schedule. Taken orally days 1-21 every 28 days until progression

Intervention: Drug: melphalan Dose determined by Phase I treatment schedule. Taken orally days 1-4 every 28 days until progression

Intervention: Drug: prednisone 60mg/m^2, orally days 1-4 every 28 days until progression

Drug: lenalidomide

Phase I - dose escalating: 5mg level -1, 10mg level 0, 10mg level 1, 15mg level 2, 20mg level 3, 25mg level 4, orally days 1-21 every 28 days until progression

Phase II - 10 mg orally days 1-21 every 28 days until progression

Drug: melphalan

Phase I - dose escalating: 5mg/m^2 dose level -1, 5 mg/m^2 dose level 0, 8 mg/m^2 dose level 1 - 4, daily x 4 orally days every 28 days until progression

Phase II - 5mg/m^2 orally days 1-4 every 28 days until progression

Drug: prednisone
60mg/m^2, orally days 1-4 every 28 days until progression

Detailed Description:



  • Determine the maximum tolerated dose of melphalan and lenalidomide in combination with prednisone in patients with newly diagnosed multiple myeloma.
  • Determine the response rate in patients treated with this regimen. Secondary
  • Determine the toxicity of this regimen in these patients. OUTLINE: This is a dose-escalation study of melphalan and lenalidomide followed by a phase II study.
  • Phase I: Patients receive oral melphalan and oral prednisone daily on days 1-4. Patients also receive oral lenalidomide daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of melphalan and lenalidomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

* Phase II: Patients receive oral melphalan and oral lenalidomide as in phase I at the MTD. Patients also receive oral prednisone as in phase I. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 3 years.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Diagnosis of multiple myeloma

    • Newly diagnosed disease
    • Requires treatment, in the judgment of the treating physician
    • Not a candidate for (or patient declines) autologous stem cell transplantation
  • Meets 1 of the following criteria:

    • Measurable disease, defined by any of the following:

      • Serum monoclonal protein ≥ 1 g/dL
      • Urine protein monoclonal light chain ≥ 200 mg/24 hours by electrophoresis
      • Measurable serum free light chains ≥ 10 mg/dL, kappa or lambda, AND κ/λ ratio is abnormal (if serum and urine are not measurable as defined above)
    • Evaluable disease, defined as monoclonal bone marrow plasmacytosis ≥ 30%


  • ECOG performance status 0-3
  • Life expectancy > 3 months
  • ANC ≥ 1,500/mm³
  • Bilirubin ≤ 2.0 mg/dL
  • Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
  • AST ≤ 3 times ULN
  • Creatinine ≤ 3.0 mg/dL
  • Platelet count ≥ 100,000/mm³
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use 2 effective methods of contraception, including ≥ 1 highly effective method, ≥ 4 weeks before and during study treatment
  • No uncontrolled infection
  • No peripheral neuropathy ≥ grade 2
  • No serious medical condition, laboratory abnormality, or psychiatric illness that would preclude study compliance
  • No other active malignancy except for nonmelanoma skin cancer or carcinoma in situ

    - Prior malignancy allowed if treated with curative intent and is free of disease for a period appropriate for that cancer

  • No known hypersensitivity to thalidomide
  • No known HIV positivity
  • No infectious hepatitis A, B or C
  • No history of deep vein thrombosis or other medical condition requiring the use of warfarin
  • Able to take daily prophylactic acetylsalicylic acid (81 or 325 mg)


  • See Disease Characteristics
  • More than 4 weeks since prior radiotherapy for treatment of multiple myeloma
  • No prior lenalidomide
  • No other concurrent anticancer agents or treatments
  • No concurrent steroids except prednisone ≤ 20 mg/day (or the equivalent) for concurrent illness or adrenal replacement therapy
  • No other concurrent investigational therapy or agent for treatment of multiple myeloma
  • No concurrent warfarin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00477750

United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259-5499
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Study Chair: Vivek Roy, MD, FACP Mayo Clinic
Principal Investigator: Philip R. Greipp, MD Mayo Clinic
Principal Investigator: Craig B. Reeder, MD Mayo Clinic
  More Information

Responsible Party: Mayo Clinic Identifier: NCT00477750     History of Changes
Other Study ID Numbers: CDR0000546642  P30CA015083  MC038A  2387-04  RV-MM-PI-025 
Study First Received: May 23, 2007
Results First Received: November 8, 2010
Last Updated: October 1, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Vascular Diseases
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Growth Inhibitors processed this record on May 03, 2016