Clinical trial NCT00477750: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-05-24
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Patients With Overall Confirmed Response
timeFrame: Every cycle during treatment
Secondary outcomes:
measure: Progression-free Survival
timeFrame: registration to progressive disease (up to 3 years)
measure: Overall Survival (OS) at 3 Years
timeFrame: registration to death (up to 3 years)
measure: Duration of Response (DOR)
timeFrame: from first response to progression or death (up to 3 years)
measure: Percentage of Participants With Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3)
timeFrame: Every cycle during treatment up to 3 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Vivek Roy, MD, FACP
role: STUDY_CHAIR
affiliation: Mayo Clinic
name: Philip R. Greipp, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Craig B. Reeder, MD
role: PRINCIPAL_INVESTIGATOR
References: