Lenalidomide, and Dexamethasone With or Without Daratumumab in Treating Patients With High-Risk Smoldering Myeloma

DETER-SMM

Overview

This phase III trial studies how well lenalidomide and dexamethasone works with or without daratumumab in treating patients with high-risk smoldering myeloma. Drugs used in chemotherapy, such as lenalidomide and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as daratumumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving lenalidomide and dexamethasone with daratumumab may work better in treating patients with smoldering myeloma.

SparkCures ID 999
Trial Phase Phase 3
Enrollment 288 Patients
Treatments
Tags
Trial Sponsors
  • Eastern Cooperative Oncology Group (ECOG)
Trial Collaborators
  • National Cancer Institute (NCI)
NCT Identifier

NCT03937635

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

Inclusion Criteria:

  • Patients must be diagnosed with asymptomatic high-risk smoldering multiple myeloma (SMM) within the past 12 months. High-risk is defined by any one of the following factors:
    • Abnormal serum free light chain ratio (≤ 0.125 or ≥ 8.0 and involved chain < 100 mg/L) by serum free light chain (FLC) assay
    • Serum M-protein level ≥ 3 gm/dL
    • Presence of t(4;14) or del 17p or 1q gain by conventional cytogenetics or fluorescence in situ hybridization (FISH) studies.
  • Bone marrow aspirate and/or biopsy is required to be performed within 28 days prior to randomization and must demonstrate 10-59% clonal plasma cells.
  • ≥ 1 g/dL on serum protein electrophoresis (within 28 days prior to randomization).
  • ≥ 200 mg of monoclonal protein on a 24 hour urine protein electrophoresis (within 28 days prior to randomization).
    • NOTE: In the rare situation where the serum protein electrophoresis (SPEP) is felt to be unreliable, then quantitative immunoglobulin levels on nephelometry or turbidometry can be accepted.
  • SPEP, urine protein electrophoresis (UPEP), and serum FLC are required to be performed within 28 days prior to randomization.
    • NOTE: UPEP (on a 24-hour collection) is required; no substitute method is acceptable. Urine must be followed monthly if the baseline urine M-spike is >= 200 mg/24 hour (hr), and urine in addition to serum must be followed in order to confirm a very good partial response (VGPR) or higher response.
  • Patients must have no lytic lesions, no known plasmacytoma, and no unexplained hypercalcemia (i.e., > 11 mg/dL or 1mg/dL above upper limit of normal [ULN]).
  • Hemoglobin >= 11 g/dL (within 28 days prior to randomization).
  • Platelet count >= 100,000 cells/mm^3 (within 28 days prior to randomization).
  • Absolute neutrophil count >= 1500 cells/mm^3 (within 28 days prior to randomization).
  • Calculated creatinine clearance >= 30 mL/min (within 28 days prior to randomization).
  • Bilirubin =< 1.5 mg/dL (within 28 days prior to randomization).
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 times the upper limit of normal (within 28 days prior to randomization).
  • Patients must not have any prior or concurrent systemic or radiation therapy for the treatment of myeloma. Patients must also not have contraindication to deep vein thrombosis (DVT) prophylaxis/aspirin.
  • Patients must not have more than one focal marrow lesion on magnetic resonance imaging (MRI) of either pelvis or spine.
  • Concurrent use of erythropoietin is not allowed while on study therapy.
  • Prior or glucocorticosteroid therapy for the treatment of multiple myeloma is not permitted. Prior systemic glucocorticosteroid use for the treatment of non-malignant disorders is permitted; concurrent use after registration on the study should be restricted to the equivalent of prednisone 10 mg per day. Prior or concurrent topical or localized glucocorticosteroid therapy to treat non-malignant comorbid disorders is permitted.
  • Patients must not have active, uncontrolled seizure disorder. Patients must not have had a seizure in the last 6 months.
  • Patients must not have uncontrolled intercurrent illness including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would limit compliance with the study, or a prior history of Stevens Johnson syndrome.
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
  • Patients with monoclonal gammopathy of undetermined significance are not eligible.
  • Patients must not have grade 2 or higher peripheral neuropathy per CTCAE.
  • Patients must not have active, uncontrolled infection.
  • Patients may have a history of current or previous deep vein thrombosis or pulmonary embolism but are required to take some form of anti-coagulation as prophylaxis if they are not currently on full-dose anticoagulation.
  • Patients should not have New York Heart Association classification III or IV heart failure at baseline.
  • Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been free of disease for the time period considered appropriate for cure of the specific cancer. For most diseases this time frame is 5 years.
  • Patients must agree to register into the mandatory Risk Evaluation and Mitigation Strategy (REMS) program and be willing and able to comply with the requirements of REMS.
  • Women must not be pregnant due to potential harm to the fetus from daratumumab and lenalidomide. All females of childbearing potential (FCBP) must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to the first dose of lenalidomide and again within 24 hours prior to the first dose of lenalidomide. FCBP must also agree to ongoing pregnancy testing while on treatment. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
  • Females of childbearing potential (FCBP) must either abstain from sexual intercourse for the duration of their participation in the study or agree to use TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME for 1) at least 28 days before starting study treatment; 2) while participating in the study; 3) during dose interruptions; and 4) for at least 28 days after the last dose of protocol treatment (FCBP who are assigned to Arm A and receive daratumumab must extend this contraception requirement to 3 months after the last dose of protocol treatment). Women must also agree to not breastfeed during this same time period. Men must agree to either abstain from sexual intercourse for the duration of their participation in the study or use a latex condom during sexual contact with a FCBP while participating in the study and for 28 days after the last dose of protocol treatment even if they have had a successful vasectomy. Men must also agree to abstain from donating sperm while on study treatment and for 28 days after the last dose of protocol treatment even if they have had a successful vasectomy. Both women and men must both agree to abstain from donating blood during study participation and for at least 28 days after the last dose of protocol treatment.
  • Human immunodeficiency virus (HIV)+ patients with undetectable HIV viral loads tested within 6 months are eligible.
  • Patients should not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to daratumumab, lenalidomide, or dexamethasone.

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

SparkCures Verified Accurate, up-to-date information. Learn more


Katmai Oncology Group

Anchorage, AK

Centura Penrose Hospital

Colorado Springs, CO

McKee Medical Center

Loveland, CO

Broadlawns Medical Center

Des Moines, IA

Kootenai Cancer Center

Post Falls, ID

Carle (Effingham)

Effingham, IL

Ochsner Medical Center

Jefferson, LA

Henry Ford Hospital

Detroit, MI

Mercy Health Saint Mary's

Grand Rapids, MI

Spectrum Health

Grand Rapids, MI

Allegiance Health

Jackson, MI

Borgess Medical Center

Kalamazoo, MI

Sparrow Hospital

Lansing, MI

Munson Medical Center

Traverse City, MI

Mercy Hospital

Coon Rapids, MN

Essentia Health

Deer River, MN

Unity Hospital

Fridley, MN

Health Partners Inc.

Minneapolis, MN

Monticello Cancer Center

Monticello, MN

Mayo Clinic (Rochester)

Rochester, MN

Regions Hospital

St. Paul, MN

United Hospital

St. Paul, MN

Lakeview Hospital

Stillwater, MN

Mercy Hospital Springfield

Springfield, MO

Mercy Hospital South

St. Louis, MO

CHI Health St. Francis

Grand Island, NE

Glens Falls Hospital

Glens Falls, NY

Miami Valley Hospital South

Centerville, OH

Geaugra Hospital

Chardon, OH

Doctors Hospital

Columbus, OH

Wayne Healthcare

Greenville, OH

Kettering Medical Center

Kettering, OH

Saint Ann's Hospital

Westerville, OH

Genesis HealthCare System

Zanesville, OH

Mercy Hospital Oklahoma City

Oklahoma City, OK

Bay Area Hospital

Coos Bay, OR

PeaceHealth Medical Group

Bellingham, WA

Aurora Cancer Care (Racine)

Mount Pleasant, WI

D. N. Greenwald Center

Mukwonago, WI

West Virginia University

Morgantown, WV

Welch Cancer Center

Sheridan, WY

Not Currently Accepting Patients

The following is a listing of trial locations that are not currently open and accepting patients.

Alegent Health Mercy Hospital

Council Bluffs, IA

Kootenai Clinic

Sandpoint, ID

Springmill Medical Center

Indianapolis, IN

Saint Luke's South Hospital

Overland Park, KS

Flaget Memorial Hospital

Bardstown, KY

Hematology Oncology Clinic

Baton Rouge, LA

Mercy Medical Center

Springfield, MA

Henry Ford Macomb Hospital

Clinton Township, MI

Cambridge Medical Center

Cambridge, MN

Mercy Hospital Washington

Washington, MO

CHI Health Midlands

Papillion, NE

Fairfield Medical Center

Lancaster, OH

Knox Community Hospital

Mount Vernon, OH

Geisinger Medical Group

State College, PA

Prisma Health Boiling Springs

Boiling Springs, SC

Saint Francis Hospital

Federal Way, WA

Alaska
Katmai Oncology Group

Anchorage, AK

Arizona
California
Colorado
Centura Penrose Hospital

Colorado Springs, CO

McKee Medical Center

Loveland, CO

Connecticut
Florida
Georgia
Verified Winship Cancer Institute of Emory University

SparkCures Verified Accurate, up-to-date information. Learn more


Idaho
Kootenai Cancer Center

Post Falls, ID

Kootenai Clinic

Sandpoint, ID

Illinois
Carle (Effingham)

Effingham, IL

Indiana
Springmill Medical Center

Indianapolis, IN

Iowa
Alegent Health Mercy Hospital

Council Bluffs, IA

Broadlawns Medical Center

Des Moines, IA

Kansas
Saint Luke's South Hospital

Overland Park, KS

Kentucky
Flaget Memorial Hospital

Bardstown, KY

Louisiana
Hematology Oncology Clinic

Baton Rouge, LA

Ochsner Medical Center

Jefferson, LA

Maryland
Massachusetts
Mercy Medical Center

Springfield, MA

Michigan
Henry Ford Macomb Hospital

Clinton Township, MI

Henry Ford Hospital

Detroit, MI

Mercy Health Saint Mary's

Grand Rapids, MI

Spectrum Health

Grand Rapids, MI

Allegiance Health

Jackson, MI

Borgess Medical Center

Kalamazoo, MI

Sparrow Hospital

Lansing, MI

Munson Medical Center

Traverse City, MI

Minnesota
Cambridge Medical Center

Cambridge, MN

Mercy Hospital

Coon Rapids, MN

Essentia Health

Deer River, MN

Unity Hospital

Fridley, MN