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

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00772915
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 39
• Location: 1
• Arm: 1
• Actual Duration (Months): 114.8
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: dexamethasone; Drug: lenalidomide	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Revlimid® and "On Demand" Dexamethasone Dosing in Patients With Newly Diagnosed Symptomatic Multiple Myeloma
• Actual Study Start Date: Dec 3, 2008
• Actual Primary Completion Date: Mar 22, 2011
• Actual Study Completion Date: Jun 27, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Lenalidomide with On-Demand Dexamethasone 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.

Drug: dexamethasone; 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.; Drug: lenalidomide; 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).

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) Rate at 12 Months [12 months from registration]

   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

1. Confirmed Response Rate [Up to 18 cycles from registration]

   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

2. Overall Survival (OS) [Time from registration to death (up to 3 years)]

   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

3. Progression-free Survival (PFS) [Time from registration to progression or death (up to 3 years)]

   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%)

4. Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event at Least Possibly Related to Treatment (Toxicity) [Duration on treatment (up to 18 cycles from registration)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Cancer Institute (NCI)

Investigators

• Study Chair: Shaji K. Kumar, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00772915
• Other Study ID Numbers: CDR0000616057; P30CA015083; MC0884; 08-002093; NCI-2009-01201; RV-MM-PI-367
• First Posted: Oct 15, 2008
• Last Update Posted: Jan 18, 2020
• Last Verified: Jun 1, 2018

• Keywords provided by Mayo Clinic: stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Dexamethasone; Lenalidomide

Study Results

Participant Flow

Recruitment Details	Thirty-nine (39) participants were recruited at Mayo Clinic (Rochester) between December 2008 and April 2010.
Pre-assignment Detail	One participant canceled prior to starting treatment; this participant has been removed from all analyses.

Arm/Group Title	Lenalidomide With On-Demand Dexamethasone
Arm/Group Description	Lenalidomide: 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.
Period Title: Overall Study
STARTED	38
COMPLETED	23
NOT COMPLETED	15

Baseline Characteristics

Arm/Group Title	Lenalidomide With On-Demand Dexamethasone
Arm/Group Description	Lenalidomide: 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.
Overall Participants	38
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	66
Sex: Female, Male (Count of Participants)
Female	21 55.3%
Male	17 44.7%
Region of Enrollment (participants) [Number]
United States	38 100%
Durie Salmon Stage at Diagnosis (participants) [Number]
Stage I: Low Cell Mass	8 21.1%
Stage II: Intermediate Cell Mass	15 39.5%
Stage III: High Cell Mass	12 31.6%
Not Assessed	3 7.9%
Parameter of Hematologic Response: Serum M-Spike >= 1 mg/dL (participants) [Number]
Yes	26 68.4%
No	12 31.6%
Parameter of Hematologic Response: Serum Immunoglobulin Free Light Chain >= 10 mg/dL (participants) [Number]
Yes	25 65.8%
No	13 34.2%
Parameter of Hematologic Response: Urine M-Spike >= 200 mg/24 hours (participants) [Number]
Yes	14 36.8%
No	24 63.2%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) Rate at 12 Months
Description	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%)
Time Frame	12 months from registration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide With On-Demand Dexamethasone
Arm/Group Description	Lenalidomide: 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.
Measure Participants	38
Number (95% Confidence Interval) [percentage of participants]	79 207.9%

2. Secondary Outcome

Title	Confirmed Response Rate
Description	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
Time Frame	Up to 18 cycles from registration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide With On-Demand Dexamethasone
Arm/Group Description	Lenalidomide: 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.
Measure Participants	38
Number (95% Confidence Interval) [percentage of participants]	61 160.5%

3. Secondary Outcome

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 3 years from randomization. The median OS with 95% CI was estimated using the Kaplan Meier method
Time Frame	Time from registration to death (up to 3 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide With On-Demand Dexamethasone
Arm/Group Description	Lenalidomide: 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.
Measure Participants	38
Median (95% Confidence Interval) [months]	61.1

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide With On-Demand Dexamethasone
Arm/Group Description	Lenalidomide: 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.
Measure Participants	38
Median (95% Confidence Interval) [months]	27

5. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide With On-Demand Dexamethasone
Arm/Group Description	Lenalidomide: 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.
Measure Participants	38
Count of Participants [Participants]	23 60.5%

Adverse Events

Arm/Group Title	Lenalidomide With On-Demand Dexamethasone
Arm/Group Description	Dexamethasone: 10-40 mg once weekly (days 1, 8, 15, & 22) orally with food until progression.
All Cause Mortality
	Lenalidomide With On-Demand Dexamethasone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lenalidomide With On-Demand Dexamethasone
	Affected / at Risk (%)	# Events
Total	9/38 (23.7%)
Cardiac disorders
Left ventricular failure	1/38 (2.6%)	1
Gastrointestinal disorders
Dysphagia	1/38 (2.6%)	1
General disorders
Chills	1/38 (2.6%)	1
Fatigue	1/38 (2.6%)	1
Infections and infestations
Meningitis	1/38 (2.6%)	1
Pneumonia	1/38 (2.6%)	1
Sepsis	1/38 (2.6%)	1
Injury, poisoning and procedural complications
Fracture	1/38 (2.6%)	1
Intraoperative musculoskeletal injury	1/38 (2.6%)	1
Investigations
Neutrophil count decreased	1/38 (2.6%)	1
Renal and urinary disorders
Renal Failure	1/38 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/38 (2.6%)	1
Vascular disorders
Thrombosis	2/38 (5.3%)	2
Other (Not Including Serious) Adverse Events
	Lenalidomide With On-Demand Dexamethasone
	Affected / at Risk (%)	# Events
Total	38/38 (100%)
Blood and lymphatic system disorders
Anemia	36/38 (94.7%)	311
Eye disorders
Cataract	1/38 (2.6%)	2
Gastrointestinal disorders
Colitis	1/38 (2.6%)	1
Constipation	3/38 (7.9%)	9
Diarrhea	3/38 (7.9%)	4
Gastrointestinal	1/38 (2.6%)	1
Mucositis oral	1/38 (2.6%)	1
Nausea	1/38 (2.6%)	2
General disorders
Fatigue	34/38 (89.5%)	258
Pain	1/38 (2.6%)	1
Pain-Chest	2/38 (5.3%)	2
Infections and infestations
Gallbladder (cholecystitis) infection	1/38 (2.6%)	1
Infection without neutropenia	1/38 (2.6%)	1
Pneumonia	1/38 (2.6%)	2
Skin (cellulites) infection	2/38 (5.3%)	2
Upper airway infection	3/38 (7.9%)	5
Injury, poisoning and procedural complications
Fracture	1/38 (2.6%)	1
Investigations
Alanine aminotransferase increased	1/38 (2.6%)	1
Aspartate aminotransferase increased	1/38 (2.6%)	3
Bilirubin	2/38 (5.3%)	4
Creatinine increased	1/38 (2.6%)	1
Leukopenia	33/38 (86.8%)	174
Lymphocyte count decreased	3/38 (7.9%)	12
Neutrophil count decreased	31/38 (81.6%)	171
Platelet count decreased	19/38 (50%)	108
Weight gain	1/38 (2.6%)	1
Metabolism and nutrition disorders
Dehydration	1/38 (2.6%)	1
Hypercalcemia	1/38 (2.6%)	1
Hyperglycemia	4/38 (10.5%)	8
Hypocalcemia	1/38 (2.6%)	1
Hypoglycemia	2/38 (5.3%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/38 (2.6%)	4
Back pain	2/38 (5.3%)	3
Bone pain	1/38 (2.6%)	1
Neck pain	1/38 (2.6%)	1
Nervous system disorders
Peripheral sensory neuropathy	23/38 (60.5%)	150
Syncope	1/38 (2.6%)	1
Tremor	1/38 (2.6%)	3
Psychiatric disorders
Depression	1/38 (2.6%)	8
Insomnia	3/38 (7.9%)	3
Renal and urinary disorders
Renal Failure	1/38 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/38 (2.6%)	1
Pleural effusion	1/38 (2.6%)	1
Skin and subcutaneous tissue disorders
Erythema multiforme	1/38 (2.6%)	1
Pruritus	1/38 (2.6%)	1
Rash	3/38 (7.9%)	3
Vascular disorders
Hot flashes	1/38 (2.6%)	2
Phlebitis	1/38 (2.6%)	1
Thrombosis	1/38 (2.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.