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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

cyclophosphamide

dexamethasone

lenalidomide

About this trial

This is an interventional treatment trial for Multiple Myeloma and Plasma Cell Neoplasm focused on measuring stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Mayo Clinic Scottsdale
Mayo Clinic Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lenalidomide/Cyclophosphamide/Dexamethasone

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

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%)

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.

Full Information

NCT ID

NCT00478218

First Posted

May 23, 2007

Last Updated

August 29, 2011

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00478218

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2011

Overall Recruitment Status

Completed

Study Start Date

July 2006 (undefined)

Primary Completion Date

September 2008 (Actual)

Study Completion Date

April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

53 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lenalidomide/Cyclophosphamide/Dexamethasone

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

cyclophosphamide

Other Intervention Name(s)

Cytoxan, CTX, Neosar®

Intervention Description

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)

Intervention Type

Drug

Intervention Name(s)

dexamethasone

Other Intervention Name(s)

Decadron

Intervention Description

40 mg administrated by PO (with food)on Days 1, 8, 15 & 22

Intervention Type

Drug

Intervention Name(s)

lenalidomide

Other Intervention Name(s)

Revlimid®

Intervention Description

25 mg administrated by PO (with food)on Days 1-21

Primary Outcome Measure Information:

Title

Number of Participants Who Achieved a Confirmed Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) During Treatment

Description

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

Time Frame

Duration of Treatment (up to 5 years)

Secondary Outcome Measure Information:

Title

Overall Survival (OS)

Description

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.

Time Frame

up to 5 years

Title

Progression-free Survival (PFS)

Description

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%)

Time Frame

up to 5 years

Title

Duration of Response (DOR)

Description

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.

Time Frame

up to 5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shaji K. Kumar, MD

Organizational Affiliation

Mayo Clinic

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Craig B. Reeder, MD

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic Scottsdale

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85259-5499

Country

United States

Facility Name

Mayo Clinic Cancer Center

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

21630308

Citation

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.

Results Reference

result

Multiple Myeloma and Plasma Cell Neoplasm

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial