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

NCT ID: NCT00477750

Last Updated: 2019-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2013-08-05

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

lenalidomide

Intervention Type: 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

melphalan

Intervention Type: 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

prednisone

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

prednisone

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vivek Roy, MD, FACP

Role: STUDY_CHAIR

Mayo Clinic

Philip R. Greipp, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Craig B. Reeder, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MC038A

Identifier Type: OTHER

Identifier Source: secondary_id

2387-04

Identifier Type: OTHER

Identifier Source: secondary_id

RV-MM-PI-025

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000546642

Identifier Type: -

Identifier Source: org_study_id