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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00772915
First received: October 12, 2008
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: dexamethasone
Drug: lenalidomide
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Progression-free Survival Rate at 12 Months [ Time Frame: 12 months from registration ] [ Designated as safety issue: No ]
    PFS at 12 months is a dichotomized outcome indicating whether or not a participant was progression free (and alive) at 12 months from the date of randomization.


Secondary Outcome Measures:
  • Overall Response Rate [ Time Frame: Up to 18 cycles from registration ] [ Designated as safety issue: No ]

    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) [ Time Frame: Time from registration to death (up to 3 years) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Time from registration to progression or death (up to 3 years) ] [ Designated as safety issue: No ]

    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%)

  • Adverse Events [ Time Frame: Duration on treatment (up to 18 cycles from registration) ] [ Designated as safety issue: Yes ]

Enrollment: 39
Study Start Date: December 2008
Estimated Study Completion Date: October 2014
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00772915

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Shaji K. Kumar, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00772915     History of Changes
Other Study ID Numbers: CDR0000616057, P30CA015083, MC0884, 08-002093, NCI-2009-01201, RV-MM-PI-367
Study First Received: October 12, 2008
Results First Received: June 26, 2012
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

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
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on October 19, 2014