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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma and Plasma Cell Neoplasm
• Intervention / Treatment: Drug: cyclophosphamide; Drug: dexamethasone; Drug: lenalidomide

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lenalidomide/Cyclophosphamide/Dexamethasone

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); Other Names: Cytoxan, CTX, Neosar®; Drug: dexamethasone; 40 mg administrated by PO (with food)on Days 1, 8, 15 & 22; Other Names: Decadron; Drug: lenalidomide; 25 mg administrated by PO (with food)on Days 1-21; Other Names: Revlimid®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Shaji K. Kumar, MD, Mayo Clinic; Principal Investigator: Craig B. Reeder, MD, Mayo Clinic

Publications and helpful links

General Publications

• 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, cyclophosphamide and dexamethasone (CRd) for newly diagnosed multiple myeloma: results from a phase 2 trial. Am J Hematol. 2011 Aug;86(8):640-5. doi: 10.1002/ajh.22053. Epub 2011 May 31.

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: May 23, 2007
• First Submitted That Met QC Criteria: May 23, 2007
• First Posted (Estimate): May 24, 2007

Study Record Updates

• Last Update Posted (Estimate): August 31, 2011
• Last Update Submitted That Met QC Criteria: August 29, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: stage II multiple myeloma; stage III multiple myeloma; stage I multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Cyclophosphamide; Lenalidomide
• Other Study ID Numbers: CDR0000546657; P30CA015083 (U.S. NIH Grant/Contract); MC058E (Other Identifier: Mayo Clinic Cancer Center); 06-002786 (Other Identifier: Mayo Clinic IRB); RV-MM-PI-0116 (Other Identifier: Celgene Protocol)