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

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00602641

Purpose

RATIONALE: Drugs used in chemotherapy, such as melphalan and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Thalidomide and lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. It is not yet known whether melphalan and prednisone are more effective when given together with thalidomide or lenalidomide in treating multiple myeloma.

PURPOSE: This randomized phase III trial is studying giving melphalan and prednisone together with thalidomide to see how well it works compared with giving melphalan and prednisone together with lenalidomide in treating patients with newly diagnosed multiple myeloma.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: lenalidomide Drug: melphalan Drug: prednisone Drug: thalidomide	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	An Intergroup Phase III Randomized Controlled Trial Comparing Melphalan, Prednisone and Thalidomide (MPT) Versus Melphalan, Prednisone and Lenalidomide (Revlimid™) (MPR) in Newly Diagnosed Multiple Myeloma Patients Who Are Not Candidates for High-Dose Therapy

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Thalidomide 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:

Progression-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rates and depth of response comparison [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Quality-of-life (QOL) change comparison of arms measured by FACT-Ntx TOI from baseline to course 24 [ Designated as safety issue: No ]
Differential treatment response on QOL measured by FACT-Ntx TOI from baseline to course 38 [ Designated as safety issue: No ]
TC classification validation of myeloma as a prognostic tool using gene expression profiling [ Designated as safety issue: No ]

Estimated Enrollment:	560
Study Start Date:	February 2008
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Active Comparator Patients receive oral melphalan and oral prednisone once daily on days 1-4, and oral thalidomide once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive oral thalidomide once daily and continue in the absence of disease progression.	Drug: melphalan Oral Drug: prednisone Oral Drug: thalidomide Oral
Arm II: Experimental Patients receive oral melphalan and oral prednisone once daily on days 1-4, and oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression.	Drug: lenalidomide Oral Drug: melphalan Oral Drug: prednisone Oral

Detailed Description:

OBJECTIVES:

Primary

To compare progression-free survival between patients receiving melphalan, prednisone, and thalidomide versus melphalan, prednisone, and lenalidomide in newly diagnosed multiple myeloma patients who are not candidates for high-dose therapy.

Secondary

To compare overall survival between both arms.
To compare response rates and depth of response in these patients.
To compare the incidence of toxicities in these patients.
To validate the TC classification of myeloma as a prognostic tool using gene expression profiling at diagnosis.

Tertiary

To compare quality-of-life (QOL) change between arms based on the FACT-Ntx TOI from baseline to the end of course 24 (maintenance therapy).
To examine the impact of differential treatment responses on QOL based on the FACT-Ntx TOI up to course 38.
To obtain prospective data on myeloma specific QOL attributes.

OUTLINE: This is a multicenter study. Patients are stratified according to ISS stage (I-II vs III) and age (< 65 vs ≥ 65). Patients are randomized to 1 of 2 treatment arms.

Arm I:
- Induction therapy: Patients receive oral melphalan and oral prednisone once daily on days 1-4, and oral thalidomide once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
- Maintenance therapy: Patients receive oral thalidomide once daily and continue in the absence of disease progression.
Arm II:
- Induction therapy: Patients receive oral melphalan and oral prednisone once daily on days 1-4, and oral lenalidomide on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
- Maintenance therapy: Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression.

Quality of life is assessed at baseline and periodically during treatment.

Peripheral blood and bone marrow samples are collected at baseline for gene expression profiling analysis.

After completion of study treatment, patients will be followed periodically for 10 years.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Newly diagnosed multiple myeloma (MM), meeting the following criteria:
- Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma
- Symptomatic disease with evidence of end-organ damage at initial diagnosis that prompted the initiation of therapy, including ≥ 1 of the following:
  - Anemia
  - Hypercalcemia
  - Bone disease (lytic bone lesions or pathologic fracture)
  - Renal dysfunction
No smoldering MM, defined by all of the following:
- Serum monoclonal protein ≥ 3 g/dL
- Bone marrow plasma cells ≥ 10% or greater
- Absence of anemia, hypercalcemia, lytic bone lesions, or renal dysfunction
No monoclonal gammopathy of undetermined significance, defined by all of the following:
- Serum monoclonal protein < 3 g/dL
- Bone marrow plasma cells ≤ 10%
- Absence of anemia, hypercalcemia, lytic bone lesions, or renal dysfunction
Previously untreated for MM
Patients 18 to 64 years old must not be a candidate for autologous stem cell transplantation or have declined transplantation or other alternative treatment

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Hemoglobin > 7 g/dL
Platelet count > 75,000/mm³
ANC > 1,000/mm³
Creatinine < 2.5 mg/dL AND creatinine clearance (measured or calculated) ≥ 60 mL/min
Direct bilirubin ≤ 1.5 mg/dL
ALT and AST ≤ 2.5 times upper limit of normal
No uncontrolled intercurrent illness that would limit compliance with the study including, but not limited to, any of the following:
- Uncontrolled hypertension
- Symptomatic congestive heart failure
- Unstable angina
- Uncontrolled cardiac arrhythmia
- Uncontrolled psychiatric illness or social situation
- Prior history of Stevens Johnson syndrome
No peripheral neuropathy ≥ grade 2
No active uncontrolled infection
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective double-barrier contraception 4 weeks prior to, during, and 4 weeks after completion of study treatment
Must be able to take prophylactic aspirin 325mg/day or low-molecular weight heparin or coumadin
No second active malignancy requiring treatment within the past 2 years, except for basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior treatment for myeloma except for either of the following:
- Prednisone or dexamethasone treatment for myeloma for a duration of less than 4 weeks
- Prednisone or dexamethasone in combination with thalidomide or lenalidomide for a duration of less than 2 weeks total
Concurrent bisphosphonates or growth factors (i.e., erythropoietin) for MM allowed
Concurrent localized radiation therapy is allowed for pain control at the physician's discretion

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00602641

Show 230 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	A. Keith Stewart, MD	Mayo Clinic
Investigator:	S. V. Rajkumar, 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:	ECOG Group Chair's Office ( Robert L. Comis )
Study ID Numbers:	CDR0000583984, ECOG-E1A06
Study First Received:	January 18, 2008
Last Updated:	February 6, 2010
ClinicalTrials.gov Identifier:	NCT00602641 History of Changes
Health Authority:	Unspecified

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
Anti-Infective Agents
Melphalan
Prednisone
Molecular Mechanisms of Pharmacological Action
Thalidomide
Immunologic Factors
Blood Protein Disorders
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Paraproteinemias
Hemostatic Disorders
Hormones
Anti-Bacterial Agents

Hemorrhagic Disorders
Therapeutic Uses
Cardiovascular Diseases
Growth Inhibitors
Angiogenesis Modulating Agents
Alkylating Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Growth Substances
Vascular Diseases
Lenalidomide
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on February 08, 2010