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

NCT00477750 | Completed Phase 1 Results

• 5 other identifiers: CDR0000546642P30CA015083MC038A2387-04RV-MM-PI-025
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 3

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma

Outcome Measures

Primary Outcomes (1)

• 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

  Every cycle during treatment

Secondary Outcomes (4)

• Progression-free Survival

  registration to progressive disease (up to 3 years)

• Overall Survival (OS) at 3 Years

  registration to death (up to 3 years)

• Duration of Response (DOR)

  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)

  Every cycle during treatment up to 3 years

Study Arms (1)

Treatment (Lenalidomide, Melphalan, Prednisone)

EXPERIMENTAL

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; Drug: melphalan; Drug: prednisone

Interventions

lenalidomide DRUG

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

Treatment (Lenalidomide, Melphalan, Prednisone)

melphalan DRUG

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

Treatment (Lenalidomide, Melphalan, Prednisone)

prednisone DRUG

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

Treatment (Lenalidomide, Melphalan, Prednisone)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259-5499, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Lenalidomide; Melphalan; Prednisone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Vivek Roy
• Organization: Mayo Clinic

roy.vivek@mayo.edu

Study Officials

• Vivek Roy, MD, FACP

  Mayo Clinic

  STUDY CHAIR

• Philip R. Greipp, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Craig B. Reeder, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2007
• First Posted: May 24, 2007
• Study Start: June 1, 2005
• Primary Completion: April 1, 2008
• Study Completion: August 5, 2013
• Last Updated: October 11, 2019
• Results First Posted: December 13, 2010

Record last verified: 2015-10

Locations

US (3)