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Lenalidomide With or Without Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

Primary Purpose

Multiple Myeloma and Plasma Cell Neoplasm

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

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

DISEASE CHARACTERISTICS:

Newly diagnosed multiple myeloma, meeting the following criteria:
- Symptomatic disease
- Previously untreated disease
Measurable or evaluable disease, defined by ≥ 1 of the following:
- Serum monoclonal protein ≥ 1.0 g/dL
- Monoclonal protein > 200 mg by 24-hour urine electrophoresis
- Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa:lambda free light chain ratio
- Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)
- Measurable soft tissue plasmacytoma, not previously radiated
No monoclonal gammopathy of unknown significance or asymptomatic myeloma

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-2 (PS 3 allowed if secondary to pain)
ANC ≥ 1,500/μL
Platelet count ≥ 75,000/μL
Creatinine ≤ 2.0 mg/dL
Total bilirubin ≤ 1.5 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use 2 effective forms of contraception 28 days prior to, during and 28 days after study treatment
Registered into the RevAssist® program and willing to comply with program requirements
Able to take prophylactic aspirin (325 mg/day) or warfarin or low molecular weight heparin
Willing to provide mandatory blood and bone marrow samples
Willing to return for follow up
No uncontrolled infection
No NYHA class III or IV heart failure
No active deep vein thrombosis that has not been therapeutically anticoagulated
No known hypersensitivity to thalidomide
No known HIV positivity
No known hepatitis type A, B, or C infection
No other prior active malignancy within the past 2 years, except currently treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast
No development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs

PRIOR CONCURRENT THERAPY:

At least 3 weeks since prior radiotherapy for solitary plasmacytoma
More than 28 days since other prior experimental drug or therapy
Prior clarithromycin, DHEA, anakinra, pamidronate, or zoledronic acid allowed
No prior lenalidomide
No prior cytotoxic chemotherapy
No prior corticosteroids (≥ 160 mg of dexamethasone or equivalent) for this disease
- Prior corticosteroid for nonmalignant disease allowed
- Concurrent corticosteroids allowed (≤ 20 mg/day of prednisone or equivalent)
Concurrent palliative radiotherapy for bone pain or fracture allowed
No other concurrent anticancer agents or treatments

Sites / Locations

Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lenalidomide with On-Demand Dexamethasone

Arm Description

Lenalidmoide: 25mg once daily orally with food on days 1-21 of 28 day cycle until progression or to a maximum of 18 cycles. Dexamethasone: 10-40 mg once weekly (days 1, 8, 15, & 22) orally with food until progression.

Outcomes

Primary Outcome Measures

Progression-free Survival (PFS) Rate at 12 Months

PFS rate at 12 months is defined as the percentage of participants who are alive and progression-free at 12 months. Progression is exclusively defined as a patient with progressive disease while receiving treatment with lenalidomide in combination with dexamethasone. 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%)

Secondary Outcome Measures

Confirmed Response Rate

Confirmed response rate is defined as the percentage of participants who achieved a 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

Overall Survival (OS)

OS was defined as the time from registration to death of any cause. Participants were followed for a maximum of 3 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%)

Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event at Least Possibly Related to Treatment (Toxicity)

The number of participants who experienced toxicity (defined as at least one grade 3 or higher adverse event at least possibly related to treatment) is reported below.

Full Information

NCT ID

NCT00772915

First Posted

October 12, 2008

Last Updated

January 9, 2020

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00772915

Brief Title

Lenalidomide With or Without Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

Official Title

A Phase II Trial of Revlimid® and "On Demand" Dexamethasone Dosing in Patients With Newly Diagnosed Symptomatic Multiple Myeloma

Study Type

Interventional

2. Study Status

Record Verification Date

June 2018

Overall Recruitment Status

Completed

Study Start Date

December 3, 2008 (Actual)

Primary Completion Date

March 22, 2011 (Actual)

Study Completion Date

June 27, 2018 (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 and dexamethasone may stop the growth of multiple myeloma by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well lenalidomide works with or without dexamethasone in treating patients with newly diagnosed multiple myeloma.

Detailed Description

OBJECTIVES: Primary To assess the progression-free survival at 1 year in patients with newly diagnosed symptomatic multiple myeloma treated with lenalidomide alone or in combination with dexamethasone added for disease progression or lack or partial response. Secondary To assess the response rate of this regimen in these patients. To assess the toxicity of this regimen in these patients. Tertiary To examine the effect of lenalidomide alone on tumor specific immunity and global parameters of immune function. To examine the effect of dexamethasone addition in patients requiring steroids. To correlate changes in parameters of immune response and measures of disease response. To examine the antiangiogenic activity of lenalidomide alone and in combination with dexamethasone. To examine the effect of lenalidomide alone on tumor cell survival and proliferation. OUTLINE: Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for up to 18 courses in the absence of second disease progression or unacceptable toxicity. Beginning in course 4, patients experiencing stable or progressive disease also receive concurrent oral dexamethasone once daily on days 1, 8, 15, and 22 and for all subsequent courses. Blood and bone marrow samples are collected periodically for pharmacological and correlative studies. Samples are analyzed for parameters of immune activation, cell proliferation and apoptosis, and circulating tumor cells and endothelial cells via flow cytometry; global impact of therapy on immune cell subsets via immunophenotype analysis; and angiogenesis via CD34 staining. After completion of study therapy, patients are followed periodically for up to 2 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

39 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lenalidomide with On-Demand Dexamethasone

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

dexamethasone

Intervention Description

Dose: -40 mg once weekly (days 1, 8, 15, & 22) orally with food until progression. If after 3 cycles, a partial response is not achieved on lenalidomide alone, dexamethasone 10 mg weekly will be added, and the weekly dexamethasone dose will be increased by 10 mg each cycle to a maximum of 40 mg weekly, as long as a partial response is not achieved. If a partial response is achieved at a dose of dexamethasone less than 40 mg weekly, patients will continue on that dose. If progression at any time, increase dexamethasone to 40 mg weekly. Patient will go off study only when progression is documented while receiving 40 mg/week of dexamethasone or the maximum tolerated dose of dexamethasone (if prior dose reductions have been implemented for toxicity). Increases in dexamethasone dose are to be made only at the initiation of a cycle. If progression at any time while on lenalidomide alone (first 3 cycles), add dexamethasone 40 mg weekly.

Intervention Type

Drug

Intervention Name(s)

lenalidomide

Intervention Description

25mg once daily orally with food on days 1-21 of 28 day cycle until progression or to a maximum of 18 cycles. Lenalidomide alone will be administered for the first 3 cycles, then in combination with dexamethasone as needed (described).

Primary Outcome Measure Information:

Title

Progression-free Survival (PFS) Rate at 12 Months

Description

Time Frame

12 months from registration

Secondary Outcome Measure Information:

Title

Confirmed Response Rate

Description

Time Frame

Up to 18 cycles from registration

Title

Overall Survival (OS)

Description

Time Frame

Time from registration to death (up to 3 years)

Title

Progression-free Survival (PFS)

Description

Time Frame

Time from registration to progression or death (up to 3 years)

Title

Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event at Least Possibly Related to Treatment (Toxicity)

Description

The number of participants who experienced toxicity (defined as at least one grade 3 or higher adverse event at least possibly related to treatment) is reported below.

Time Frame

Duration on treatment (up to 18 cycles from registration)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility Criteria

DISEASE CHARACTERISTICS: Newly diagnosed multiple myeloma, meeting the following criteria: Symptomatic disease Previously untreated disease Measurable or evaluable disease, defined by ≥ 1 of the following: Serum monoclonal protein ≥ 1.0 g/dL Monoclonal protein > 200 mg by 24-hour urine electrophoresis Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa:lambda free light chain ratio Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease) Measurable soft tissue plasmacytoma, not previously radiated No monoclonal gammopathy of unknown significance or asymptomatic myeloma PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-2 (PS 3 allowed if secondary to pain) ANC ≥ 1,500/μL Platelet count ≥ 75,000/μL Creatinine ≤ 2.0 mg/dL Total bilirubin ≤ 1.5 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use 2 effective forms of contraception 28 days prior to, during and 28 days after study treatment Registered into the RevAssist® program and willing to comply with program requirements Able to take prophylactic aspirin (325 mg/day) or warfarin or low molecular weight heparin Willing to provide mandatory blood and bone marrow samples Willing to return for follow up No uncontrolled infection No NYHA class III or IV heart failure No active deep vein thrombosis that has not been therapeutically anticoagulated No known hypersensitivity to thalidomide No known HIV positivity No known hepatitis type A, B, or C infection No other prior active malignancy within the past 2 years, except currently treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast No development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs PRIOR CONCURRENT THERAPY: At least 3 weeks since prior radiotherapy for solitary plasmacytoma More than 28 days since other prior experimental drug or therapy Prior clarithromycin, DHEA, anakinra, pamidronate, or zoledronic acid allowed No prior lenalidomide No prior cytotoxic chemotherapy No prior corticosteroids (≥ 160 mg of dexamethasone or equivalent) for this disease Prior corticosteroid for nonmalignant disease allowed Concurrent corticosteroids allowed (≤ 20 mg/day of prednisone or equivalent) Concurrent palliative radiotherapy for bone pain or fracture allowed No other concurrent anticancer agents or treatments

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shaji K. Kumar, MD

Organizational Affiliation

Mayo Clinic

Official's Role

Study Chair

Facility Information:

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

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Lenalidomide With or Without Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

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