- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00477750
Melphalan, Prednisone, and Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma
Phase I/II Trial of Melphalan, Prednisone Plus Lenalidomide in Patients With Newly Diagnosed Multiple Myeloma Who Are Not Candidates for Stem Cell Transplant
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Arizona
-
Scottsdale, Arizona, United States, 85259-5499
- Mayo Clinic in Arizona
-
-
Florida
-
Jacksonville, Florida, United States, 32224
- Mayo Clinic in Florida
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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 |
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 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
60mg/m^2, orally days 1-4 every 28 days until progression
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patients With Overall Confirmed Response
Time Frame: Every cycle during treatment
|
Response that was confirmed on 2 consecutive evaluations.>
|
Every cycle during treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival
Time Frame: registration to progressive disease (up to 3 years)
|
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:
|
registration to progressive disease (up to 3 years)
|
Overall Survival (OS) at 3 Years
Time Frame: registration to death (up to 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.
|
registration to death (up to 3 years)
|
Duration of Response (DOR)
Time Frame: from first response to progression or death (up to 3 years)
|
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.
|
from first response to progression or death (up to 3 years)
|
Percentage of Participants With Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3)
Time Frame: Every cycle during treatment up to 3 years
|
The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
|
Every cycle during treatment up to 3 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Vivek Roy, MD, FACP, Mayo Clinic
- Principal Investigator: Craig B. Reeder, MD, Mayo Clinic
- Principal Investigator: Philip R. Greipp, MD, Mayo Clinic
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Lenalidomide
- Prednisone
- Melphalan
Other Study ID Numbers
- CDR0000546642
- P30CA015083 (U.S. NIH Grant/Contract)
- MC038A (Other Identifier: Mayo Clinic Cancer Center)
- 2387-04 (Other Identifier: Mayo Clinic IRB)
- RV-MM-PI-025 (Other Identifier: Celgene protocol)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Myeloma and Plasma Cell Neoplasm
-
The Cleveland ClinicWithdrawnStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Plasma Cell NeoplasmUnited States
-
OncotherapeuticsWithdrawnStage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Plasma Cell NeoplasmUnited States
-
National Cancer Institute (NCI)CompletedStage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Plasma Cell NeoplasmUnited States
-
Medical Research CouncilUnknownMultiple Myeloma and Plasma Cell NeoplasmUnited Kingdom
-
LifeTime PharmaceuticalsUnknownMultiple Myeloma and Plasma Cell Neoplasm | Precancerous ConditionUnited States
-
Sidney Kimmel Comprehensive Cancer Center at Johns...National Cancer Institute (NCI)CompletedMultiple Myeloma and Plasma Cell NeoplasmUnited States
-
Jonsson Comprehensive Cancer CenterMillennium Pharmaceuticals, Inc.CompletedMultiple Myeloma and Plasma Cell NeoplasmUnited States
-
University of Maryland, BaltimoreCompletedMultiple Myeloma and Plasma Cell NeoplasmUnited States
-
Masonic Cancer Center, University of MinnesotaTerminatedMultiple Myeloma and Plasma Cell NeoplasmUnited States
-
Barbara Ann Karmanos Cancer InstituteNational Cancer Institute (NCI)TerminatedMultiple Myeloma and Plasma Cell NeoplasmUnited States
Clinical Trials on lenalidomide
-
Sidney Kimmel Comprehensive Cancer Center at Johns...TerminatedMyelodysplastic SyndromeUnited States
-
Grupo Español de Linfomas y Transplante Autólogo...Celgene Corporation; Dynamic Science S.L.; Thermo Fisher Scientific, IncCompleted
-
Celgene CorporationICON Clinical ResearchCompletedMyelodysplastic SyndromesGermany, Israel, United Kingdom, Spain, Belgium, Italy, France, Netherlands, Sweden
-
Swiss Group for Clinical Cancer ResearchTerminatedLymphomaSwitzerland, Norway, Sweden
-
Boston VA Research Institute, Inc.Celgene Corporation; Edward Hines Jr. VA Hospital; Michael E. DeBakey VA Medical... and other collaboratorsCompletedMultiple MyelomaUnited States
-
Dana-Farber Cancer InstituteBeth Israel Deaconess Medical Center; Genentech, Inc.; Brigham and Women's Hospital and other collaboratorsTerminatedWaldenstrom's MacroglobulinemiaUnited States
-
University Hospital, ToulouseCelgene Corporation; Janssen-Cilag Ltd.Completed
-
CelgeneCompletedRelapsed or Refractory Chronic Lymphocytic LeukemiaUnited States, Canada, United Kingdom, France, Germany, Spain, Italy, Sweden
-
Groupe Francophone des MyelodysplasiesUnknownMyelodysplastic SyndromesFrance