Lenalidomide, Cyclophosphamide, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

Multiple Myeloma and Plasma Cell Neoplasm Clinical Trial

Official title:

A Phase II Trial of Revlimid, Cyclophosphamide, and Dexamethasone in Patients With > Newly Diagnosed Active Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00478218
• Other study ID #: CDR0000546657
• Secondary ID: P30CA015083MC058
• Status: Completed
• Phase: Phase 2
• First received: May 23, 2007
• Last updated: August 29, 2011
• Start date: July 2006
• Est. completion date: April 2011

Study information

• Verified date: August 2011
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with cyclophosphamide and dexamethasone may kill more cancer cells.> PURPOSE: This phase II trial is studying how well giving lenalidomide together with cyclophosphamide and dexamethasone works in treating patients with newly diagnosed multiple myeloma.

Description:

OBJECTIVES:

Primary

• Assess the response rate in patients with newly diagnosed active multiple myeloma treated with lenalidomide, cyclophosphamide, and dexamethasone.

Secondary

• Assess the toxicity of this regimen in these patients.

• Determine the time to progression in patients treated with this regimen. OUTLINE:

Patients receive oral lenalidomide on days 1-21, oral cyclophosphamide on days 1, 8, and 15, and oral dexamethasone on days 1, 8, 15, and 22. Treatment repeats every 28 days for 4-12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months for up to 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: April 2011
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma

• Newly diagnosed disease

• Symptomatic disease

• Measurable or evaluable disease, defined by = 1 of the following criteria:

• Serum monoclonal protein = 1.0 g by protein electrophoresis

• Monoclonal protein > 200 mg by 24-hour urine electrophoresis

• Serum immunoglobulin free light chain = 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio

• Monoclonal bone marrow plasmacytosis = 30% (evaluable disease)

• Measurable soft tissue plasmacytoma not previously irradiated

• No monoclonal gammopathy of undetermined significance or smoldering myeloma

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 (ECOG PS 3 allowed if secondary to pain)

• ANC = 1,500/mm^3

• Platelet count = 75,000/mm^3

• Hemoglobin = 8.0 g/dL

• Creatinine = 2.5 mg/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective double-method contraception (1 highly effective and 1 additional method) for 1 month before, during, and for 4 weeks after completion of study therapy

• No uncontrolled infection

• No other active malignancy

• No other malignancies within the past 5 years except for currently treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast

• No NYHA class III-IV congestive heart failure

• No untreated active deep vein thrombosis

PRIOR CONCURRENT THERAPY:

• At least 3 weeks since prior radiotherapy for solitary plasmacytoma

• Prior clarithromycin, therapeutic dehydroepiandrosterone (DHEA), anakinra, pamidronate disodium, or zoledronic acid allowed

• No prior cytotoxic chemotherapy

• No prior corticosteroids (except for treatment of a nonmalignant disorder)

• Concurrent corticosteroids (prednisone = 20 mg/per day) allowed

• No concurrent radiotherapy except palliative radiotherapy for a single painful bone lesion or fracture

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

Drug:
• cyclophosphamide
300 mg/m2 administrated by PO (with food)on Days 1, 8, 15 (up to 12 cycles) OR 300 mg administrated by PO (with food)on Days 1, 8, 15 (up to 12 cycles)
• dexamethasone
40 mg administrated by PO (with food)on Days 1, 8, 15 & 22
• lenalidomide
25 mg administrated by PO (with food)on Days 1-21

Locations

Country	Name	City	State
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kumar SK, Lacy MQ, Hayman SR, Stewart K, Buadi FK, Allred J, Laumann K, Greipp PR, Lust JA, Gertz MA, Zeldenrust SR, Bergsagel PL, Reeder CB, Witzig TE, Fonseca R, Russell SJ, Mikhael JR, Dingli D, Rajkumar SV, Dispenzieri A. Lenalidomide, cyclophosphamid — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Achieved a Confirmed Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) During Treatment	Response that was confirmed on 2 consecutive evaluations during treatment; Complete Response(CR): Complete disappearance of M-protein from serum & urine on immunofixation, normalization of Free Light Chain (FLC) ratio & <5% plasma cells in bone marrow (BM); Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <100 mg per 24 hours; <=5% plasma cells in BM; Partial Response PR): >= 50% reduction in serum M-Component and/or Urine M-Component >= 90% reduction or <200 mg per 24 hours; or >= 50% decrease in difference between involved and uninvolved FLC levels	Duration of Treatment (up to 5 years)	No
Secondary	Overall Survival (OS)	OS was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from randomization. The median OS with 95%CI was estimated using the Kaplan Meier method.	up to 5 years	No
Secondary	Progression-free Survival (PFS)	PFS was defined as the time from registration to progression or death due to any cause. The median PFS with 95%CI was estimated using the Kaplan Meier method.; >; Progression was defined as any one or more of the following: >; An increase of 25% from lowest confirmed response in: Serum M-component (absolute increase >= 0.5g/dl); Urine M-component (absolute increase >= 200mg/24hour; Difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl; Bone marrow plasma cell percentage (absolute increase of >=10%)	up to 5 years	No
Secondary	Duration of Response (DOR)	Duration of response was calculated from the documentation (date) of first response (CR, VGPR, or PR) until the date of progression or last follow-up in the subset of patients who responded. The median DOR with 95%CI was estimated using the Kaplan Meier method.	up to 5 years	No