Carfilzomib, Lenalidomide, and Dexamethasone for Smoldering Multiple Myeloma

NCT01572480 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 12010712-C-0107
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Multiple myeloma is a blood cancer that affects the plasma cells. These cells help produce antibodies and fight infection. Smoldering multiple myeloma (SMM) is a related condition that may develop into multiple myeloma. The current standard of care for SMM is close follow-up without treatment until multiple myeloma develops. However, researchers are studying possible treatments for SMM itself. One possible treatment involves a combination of cancer treatment drugs.
• Lenalidomide is a drug that may help reduce or prevent the growth of cancer cells. Dexamethasone is a steroid that is often given with other anti-cancer drugs. These two drugs are an approved treatment for multiple myeloma that has not responded to at least one other treatment. Carfilzomib is an experimental drug that has been effective in treating multiple myeloma. Researchers want to combine these three drugs to see if they are a safe and effective treatment for SMM. Objectives: \- To see if carfilzomib, lenalidomide, and dexamethasone are a safe and effective treatment for smoldering multiple myeloma. Eligibility: \- Individuals at least 18 years of age who have SMM that is likely to progress to multiple myeloma. Design:
• Participants will be screened with a physical exam and medical history. They will also have blood and urine tests, and baseline bone marrow scans. Bone marrow samples will also be collected.
• Participants will have eight 28-day cycles of treatment with the three study drugs. The drugs will be given as tablets or as infusions. Treatment will be monitored with frequent blood tests and study visits.
• After the first four cycles, participants who are eligible for a stem cell transplant will have their stem cells collected and stored for future use.
• At the end of eight cycles, participants whose disease has not progressed will have up to 12 more cycles of treatment with lenalidomide tablets alone.

Conditions

Multiple Myeloma

Keywords

Proteasome Inhibitor; Immunomodulatory Agents; Combination Therapy; Anti-Myeloma Activity

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Minimal Residual Disease (MRD)Negative Complete Response (CR) Per International Myeloma Working Group (IMWG) Criteria

  MRDnegative Complete Response (CR) per the IMWHG criteria is defined as absence of phenotypically aberrant clonal plasma cells by flow cytometry on bone marrow aspirates using the eight-color two tube approach with a minimum sensitivity of 1 in 10\^5 nucleated cells or higher.

  8 months

Secondary Outcomes (6)

• Percentage of Participants That Have Minimal Residual Disease (MRD)-Negative Complete Response (CR) for a Minimum of 1 Year

  1 year

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately 117 months and 1 day.

• Clinical Progression Free Survival

  time from enrollment in the study until development of overt clinical multiple myeloma (end organ damage or myeloma-defining event) or death, up to 5 years

• Biochemical Progression Free Survival

  time from enrollment in the study until development of overt clinical multiple myeloma (end organ damage or myeloma-defining event) or death, and progressive disease by IMWG criteria, up to 5 years

• Duration of Response

  through study completion, for a maximum of 12 years and 7 days

Study Arms (2)

Group A - (closed) - Carfilzomib with Revlimid and Dexamethasone

EXPERIMENTAL

Carfilzomib (intravenous (IV), Days 1, 2, 8, 9, 15, and 16 of the 28-day cycle); Revlimid (by mouth (PO), Days 1-21 of the 28-day cycle; exception: not given on cycle 1 day 1); and Dexamethasone (PO or IV, Days 1, 2, 8, 9, 15, 16, 22, and 23 of the 28-day cycle; exception: not given on cycle 1 day 1)

Drug: Carfilzomib; Drug: Revlimid; Drug: Dexamethasone

Group B - Carfilzomib with Revlimid and Dexamethasone

EXPERIMENTAL

Carfilzomib (intravenous (IV), Days 1, 2, 8, 9, 15, and 16 of the 28-day cycle); Revlimid (by mouth (PO), Days 1-21 of the 28-day cycle); and Dexamethasone (PO or IV, Days 1, 2, 8, 9, 15, 16, 22, and 23 of the 28-day cycle)

Drug: Carfilzomib; Drug: Revlimid; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Carfilzomib intravenous (IV) 20-36 mg/m\^2 per dose on days 1, 2, 8, 9, 15, and 16 of each cycle based on arm; until disease progression or unacceptable toxicity.

Also known as: Kyprolis

Group A - (closed) - Carfilzomib with Revlimid and Dexamethasone; Group B - Carfilzomib with Revlimid and Dexamethasone

Revlimid DRUG

Revlimid by mouth (PO) 25 mg/day, days 1-21 every 28 days of each cycle based on arm; until disease progression or unacceptable toxicity.

Also known as: Lenalidomide

Group A - (closed) - Carfilzomib with Revlimid and Dexamethasone; Group B - Carfilzomib with Revlimid and Dexamethasone

Dexamethasone DRUG

Dexamethasone by mouth (PO) 20 mg per dose on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle based on arm; until disease progression or unacceptable toxicity.

Also known as: Ozurdex

Group A - (closed) - Carfilzomib with Revlimid and Dexamethasone; Group B - Carfilzomib with Revlimid and Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed Smoldering Multiple Myeloma confirmed by the Laboratory of Pathology, national Cancer Institute (NCI) or the Department of Laboratory Medicine, Clinical Center (CC) based on the International Myeloma Working Group Criteria:
• Serum M-protein greater than or equal to 3 g/dl and/or bone marrow plasma cells greater than or equal 10% and \<60%
• Absence of anemia: Hemoglobin \>10 g/dl
• Absence of renal failure: serum creatinine \< 2.0 mg/dL
• Absence of hypercalcemia: Calcium (Ca) \<10.5 mg/dl
• Absence of lytic bone lesion on X-ray, computed tomography (CT), or positron-emission tomography (PET)/CT and not more than 1 lesion on spinal magnetic resonance imaging (MRI). (NOTE: At the discretion of the investigator, PET/CT may replace MRI in patients who have a contraindication to MRI.)
• Involved-un-involved light chain ratio must be \<100
• Measurable disease within the past 4 weeks defined by any one of the following:
• Serum monoclonal protein greater than or equal to 1.0 g/dl
• Urine monoclonal protein \>200 mg/24 hour
• Serum immunoglobulin free light chain \>10 mg/dL AND abnormal kappa/lambda ratio
• NOTE: As of Amendment L (version date 05/17/2018), the primary endpoint is minimal residual disease (MRD(-) Complete Response (CR) rate; therefore, per the discretion of the Principal Investigator, patients without measurable disease (e.g., M-spike \<1) may also be enrolled. This is in line with the most recent International Myeloma Working Group (IMWG) multiple myeloma (MM) response criteria.
• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of carfilzomib in combination with lenalidomide in patients \<18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
• Patients must have normal organ and marrow function as defined below:

You may not qualify if:

• Patients who are receiving any other investigational agents.
• Concurrent systemic treatment or prior therapy within 4 weeks for SMM
• \- Treatment with corticosteroids for other indications is permitted
• Patients with a diagnosis of MM as defined by the 2014 IMWH diagnostic criteria.
• Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to carfilzomib or lenalidomide agents used in study, such as bortezomib or thalidomide, in addition to patients with known allergy to sulfobutyl ether \<=- cyclodextrin (Captisol).
• Uncontrolled hypertension or diabetes
• Pregnant or lactating females. Pregnant women are excluded from this study. The effects of carfilzomib on a developing human fetus are unknown. Lenalidomide is teratogenic with unknown potential for abortifacient effects. Breastfeeding women and women planning on breastfeeding may not participate. No studies of carfilzomib have been conducted on breast feeding women and it is not known if it is excreted in milk. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Carfilzomib/Lenalidomide, breastfeeding should be discontinued if the mother is treated with Carfilzomib/Lenalidomide.
• Significant cardiovascular disease with New York Heart Association (NYHA) Class II, III or IV symptoms, or hypertrophic cardiomegaly, or restrictive cardiomegaly, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia
• Active hepatitis B or C infection
• Has refractory gastrointestinal (GI) disease with refractory nausea/vomiting, inflammatory bowel disease, or bowel resection that would prevent absorption
• Significant neuropathy \>Grade 2 at the time of first dose or within 14 days of enrollment.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations within 2 weeks that would limit compliance with study requirements.
• History of other malignancy (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma) except if the patient has been free of symptoms and without active therapy during at least 2 years or if, at the clinical discretion of the investigator, the risks of this study do not outweigh the potential benefits on a case to case basis.
• Major surgery within 1 month prior to enrollment.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (7)

• Perez-Persona E, Vidriales MB, Mateo G, Garcia-Sanz R, Mateos MV, de Coca AG, Galende J, Martin-Nunez G, Alonso JM, de Las Heras N, Hernandez JM, Martin A, Lopez-Berges C, Orfao A, San Miguel JF. New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood. 2007 Oct 1;110(7):2586-92. doi: 10.1182/blood-2007-05-088443. Epub 2007 Jun 18.

  PMID: 17576818 BACKGROUND

• Dispenzieri A, Kyle RA, Katzmann JA, Therneau TM, Larson D, Benson J, Clark RJ, Melton LJ 3rd, Gertz MA, Kumar SK, Fonseca R, Jelinek DF, Rajkumar SV. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood. 2008 Jan 15;111(2):785-9. doi: 10.1182/blood-2007-08-108357. Epub 2007 Oct 17.

  PMID: 17942755 BACKGROUND

• Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, Kroger N, Einsele H, Vesole DH, Dimopoulos M, San Miguel J, Avet-Loiseau H, Hajek R, Chen WM, Anderson KC, Ludwig H, Sonneveld P, Pavlovsky S, Palumbo A, Richardson PG, Barlogie B, Greipp P, Vescio R, Turesson I, Westin J, Boccadoro M; International Myeloma Working Group. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010 Jun;24(6):1121-7. doi: 10.1038/leu.2010.60. Epub 2010 Apr 22.

  PMID: 20410922 BACKGROUND

• Kazandjian D, Diamond B, Papadimitriou M, Hill E, Sklavenitis-Pistofidis R, Ziccheddu B, Blaney P, Chojnacka M, Durante M, Maclachlan K, Young R, Usmani S, Davies F, Getz G, Ghobrial I, Korde N, Morgan G, Maura F, Landgren O. Genomic Profiling to Contextualize the Results of Intervention for Smoldering Multiple Myeloma. Clin Cancer Res. 2024 Oct 1;30(19):4482-4490. doi: 10.1158/1078-0432.CCR-24-0210.

  PMID: 38652812 DERIVED

• Kazandjian D, Hill E, Dew A, Morrison C, Roswarski J, Korde N, Emanuel M, Petrosyan A, Bhutani M, Calvo KR, Dulau-Florea A, Kwok M, Lee MJ, Lee S, Lindenberg L, Mailankody S, Manasanch E, Maric I, Mena E, Patel N, Tageja N, Trepel JB, Turkbey B, Wang HW, Wang W, Yuan C, Zhang Y, Braylan R, Choyke P, Stetler-Stevenson M, Steinberg SM, Figg WD Sr, Roschewski M, Landgren O. Carfilzomib, Lenalidomide, and Dexamethasone Followed by Lenalidomide Maintenance for Prevention of Symptomatic Multiple Myeloma in Patients With High-risk Smoldering Myeloma: A Phase 2 Nonrandomized Controlled Trial. JAMA Oncol. 2021 Nov 1;7(11):1678-1685. doi: 10.1001/jamaoncol.2021.3971.

  PMID: 34529025 DERIVED

• Bhutani M, Turkbey B, Tan E, Korde N, Kwok M, Manasanch EE, Tageja N, Mailankody S, Roschewski M, Mulquin M, Carpenter A, Lamping E, Minter AR, Weiss BM, Mena E, Lindenberg L, Calvo KR, Maric I, Usmani SZ, Choyke PL, Kurdziel K, Landgren O. Bone marrow abnormalities and early bone lesions in multiple myeloma and its precursor disease: a prospective study using functional and morphologic imaging. Leuk Lymphoma. 2016 May;57(5):1114-21. doi: 10.3109/10428194.2015.1090572. Epub 2016 Apr 7.

  PMID: 26690712 DERIVED

• Korde N, Roschewski M, Zingone A, Kwok M, Manasanch EE, Bhutani M, Tageja N, Kazandjian D, Mailankody S, Wu P, Morrison C, Costello R, Zhang Y, Burton D, Mulquin M, Zuchlinski D, Lamping L, Carpenter A, Wall Y, Carter G, Cunningham SC, Gounden V, Sissung TM, Peer C, Maric I, Calvo KR, Braylan R, Yuan C, Stetler-Stevenson M, Arthur DC, Kong KA, Weng L, Faham M, Lindenberg L, Kurdziel K, Choyke P, Steinberg SM, Figg W, Landgren O. Treatment With Carfilzomib-Lenalidomide-Dexamethasone With Lenalidomide Extension in Patients With Smoldering or Newly Diagnosed Multiple Myeloma. JAMA Oncol. 2015 Sep;1(6):746-54. doi: 10.1001/jamaoncol.2015.2010.

  PMID: 26181891 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Lenalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Dr. Elizabeth Hill
• Organization: National Cancer Institute

Elizabeth.Hill@nih.gov

240-760-6183

Study Officials

• Elizabeth Hill, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 5, 2012
• First Posted: April 6, 2012
• Study Start: May 29, 2012
• Primary Completion: March 3, 2022
• Study Completion: February 28, 2025
• Last Updated: March 10, 2026
• Results First Posted: September 13, 2022

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (1)