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

Phase 1
Completed
Conditions
Multiple Myeloma and Plasma Cell Neoplasm
Interventions
Registration Number
NCT00477750
Lead Sponsor
Mayo Clinic
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
33
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (Lenalidomide, Melphalan, Prednisone)melphalanIntervention: 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
Treatment (Lenalidomide, Melphalan, Prednisone)prednisoneIntervention: 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
Treatment (Lenalidomide, Melphalan, Prednisone)lenalidomideIntervention: 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
Primary Outcome Measures
NameTimeMethod
Patients With Overall Confirmed ResponseEvery cycle during treatment

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
NameTimeMethod
Percentage of Participants With Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3)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.

Progression-free Survivalregistration 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:

* 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%)

Duration of Response (DOR)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.

Overall Survival (OS) at 3 Yearsregistration 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.

Trial Locations

Locations (3)

Mayo Clinic in Arizona

🇺🇸

Scottsdale, Arizona, United States

Mayo Clinic in Florida

🇺🇸

Jacksonville, Florida, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

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