search
Back to results

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

Primary Purpose

Multiple Myeloma and Plasma Cell Neoplasm

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
lenalidomide
melphalan
prednisone
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma and Plasma Cell Neoplasm focused on measuring stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • 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%

PATIENT CHARACTERISTICS:

  • 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)

PRIOR CONCURRENT THERAPY:

  • 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

Sites / Locations

  • Mayo Clinic in Arizona
  • Mayo Clinic in Florida
  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (Lenalidomide, Melphalan, Prednisone)

Arm Description

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

Outcomes

Primary Outcome Measures

Patients With Overall Confirmed Response
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

Progression-free Survival
Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression was defined as any one or more of the following: An increase of 25% from lowest confirmed response in: Serum M-component (absolute increase >= 0.5g/dl) Urine M-component (absolute increase >= 200mg/24hour Difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl Bone marrow plasma cell percentage (absolute increase of >=10%)
Overall Survival (OS) at 3 Years
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. The overall survival at 3 years (a percentage) is reported below.
Duration of Response (DOR)
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.
Percentage of Participants With Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3)
The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.

Full Information

First Posted
May 23, 2007
Last Updated
September 18, 2019
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00477750
Brief Title
Melphalan, Prednisone, and Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
August 5, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
Detailed Description
OBJECTIVES: Primary 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma and Plasma Cell Neoplasm
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (Lenalidomide, Melphalan, Prednisone)
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
lenalidomide
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Description
60mg/m^2, orally days 1-4 every 28 days until progression
Primary Outcome Measure Information:
Title
Patients With Overall Confirmed Response
Description
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
Time Frame
Every cycle during treatment
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression was defined as any one or more of the following: An increase of 25% from lowest confirmed response in: Serum M-component (absolute increase >= 0.5g/dl) Urine M-component (absolute increase >= 200mg/24hour Difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl Bone marrow plasma cell percentage (absolute increase of >=10%)
Time Frame
registration to progressive disease (up to 3 years)
Title
Overall Survival (OS) at 3 Years
Description
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. The overall survival at 3 years (a percentage) is reported below.
Time Frame
registration to death (up to 3 years)
Title
Duration of Response (DOR)
Description
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.
Time Frame
from first response to progression or death (up to 3 years)
Title
Percentage of Participants With Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3)
Description
The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
Time Frame
Every cycle during treatment up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: 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% PATIENT CHARACTERISTICS: 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) PRIOR CONCURRENT THERAPY: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vivek Roy, MD, FACP
Organizational Affiliation
Mayo Clinic
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Philip R. Greipp, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Craig B. Reeder, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259-5499
Country
United States
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs