Melphalan, Prednisone, and Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00477750

Purpose

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.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: lenalidomide Drug: melphalan Drug: prednisone	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Prednisone Lenalidomide CC 5013 Melphalan Sarcolysin Melphalan hydrochloride

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Dose-limiting toxicities (Phase I) [ Designated as safety issue: Yes ]
Confirmed response (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to progression (Phase II) [ Designated as safety issue: No ]
Overall survival (Phase II) [ Designated as safety issue: No ]
Duration of response (Phase II) [ Designated as safety issue: No ]
Toxicity as measured by NCI CTCAE v 3.0 (Phase II) [ Designated as safety issue: Yes ]

Estimated Enrollment:	69
Study Start Date:	June 2005
Estimated Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00477750

Locations

United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259-5499
United States, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:	Vivek Roy, MD, FACP	Mayo Clinic
Investigator:	Philip R. Greipp, MD	Mayo Clinic
Investigator:	Craig B. Reeder, MD	Mayo Clinic
Investigator:	Angela Dispenzieri, MD	Mayo Clinic
Investigator:	Rafael Fonseca, MD	Mayo Clinic
Investigator:	Morie A. Gertz, MD	Mayo Clinic
Investigator:	Martha Q. Lacy, MD	Mayo Clinic
Investigator:	John A. Lust, MD, PhD	Mayo Clinic
Investigator:	S. V. Rajkumar, MD	Mayo Clinic
Investigator:	Thomas E. Witzig, MD	Mayo Clinic
Investigator:	Steve Zeldenrust, MD	Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Mayo Clinic - Jacksonville ( Vivek Roy )
Study ID Numbers:	CDR0000546642, MAYO-MC038A, MAYO-IRB-2387-04
Study First Received:	May 23, 2007
Last Updated:	June 5, 2009
ClinicalTrials.gov Identifier:	NCT00477750 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Melphalan
Prednisone
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Blood Protein Disorders
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Paraproteinemias
Hemostatic Disorders
Hormones
Hemorrhagic Disorders
Therapeutic Uses
Cardiovascular Diseases

Alkylating Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Vascular Diseases
Lenalidomide
Glucocorticoids
Immunosuppressive Agents
Pharmacologic Actions
Multiple Myeloma
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on February 08, 2010