Carfilzomib, Lenalidomide, and Dexamethasone Before and After Stem Cell Transplant in Treating Patients With Newly Diagnosed Multiple Myeloma

NCT01816971 | Completed Phase 2 Results

• 2 other identifiers: 12-1725NCI-2012-02023
• Study Type: interventional
• Target: 76
• Locations: 2 countries
• Sites: 5

Brief Summary

This phase II trial studies how well carfilzomib, lenalidomide, and dexamethasone before and after stem cell transplant works in treating patients with newly diagnosed multiple myeloma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from diving. Giving carfilzomib, lenalidomide, and dexamethasone before and after stem cell transplant may kill more cancer cells

Conditions

Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Achieving sCR

  The percentage of stringent complete response (CR) (sCR) will be reported along with 95% confidence intervals, adjusted for the two-stage nature of the trial design.

  Day 224

Secondary Outcomes (5)

• Overall Response Rate, Defined as at Least a Partial Response to Therapy (> PR), at Least Very Good Partial Response (VGPR) and at Least Near Complete Response (nCR) Rate

  Up to 5 years

• Time to Progression

  Up to 5 years

• Duration of Response

  Up to 5 years

• Percentage of Participants With Progression-free Survival (PFS)

  Up to 5 years

• Percentage of Participants With Overall Survival (OS)

  Up to 5 years

Study Arms (1)

Treatment (dexamethasone, carfilzomib, lenalidomide)

EXPERIMENTAL

INDUCTION THERAPY: Patients receive dexamethasone IV or PO QD on days 1, 8, 15 and 22; carfilzomib IV over 10-30 minutes on days 1, 2, 8, 9, 15, and 16; and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.. TRANSPLANT: Patients undergo autologous stem cell transplant. CONSOLIDATION THERAPY: Patients receive dexamethasone, carfilzomib, and lenalidomide as in induction. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive dexamethasone and lenalidomide as in induction therapy and carfilzomib IV over 30 minutes on days 1, 2, 15, and 16. Treatment repeats every 28 days for 10 courses in the absence of disease progression or unacceptable toxicity.

Drug: dexamethasone; Drug: carfilzomib; Drug: lenalidomide; Procedure: autologous hematopoietic stem cell transplantation; Other: laboratory biomarker analysis

Interventions

dexamethasone DRUG

Given IV or PO

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

Treatment (dexamethasone, carfilzomib, lenalidomide)

carfilzomib DRUG

Given IV

Also known as: Kyprolis, PR-171

Treatment (dexamethasone, carfilzomib, lenalidomide)

lenalidomide DRUG

Given PO

Also known as: CC-5013, IMiD-1, Revlimid

Treatment (dexamethasone, carfilzomib, lenalidomide)

autologous hematopoietic stem cell transplantation PROCEDURE

Undergo autologous hematopoietic stem cell transplant

Treatment (dexamethasone, carfilzomib, lenalidomide)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (dexamethasone, carfilzomib, lenalidomide)

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed, myeloma requiring systemic chemotherapy as per International Myeloma Working Group (IMWG) uniform criteria:
• Prior treatment of hypercalcemia or spinal cord compression or active and/or aggressively progressing myeloma with corticosteroids or lenalidomide or bortezomib-based regimens does not disqualify the patient (the treatment dose should not exceed the equivalent of 160 mg of dexamethasone in a 4 week period or not more than 1 cycle)
• Bisphosphonates are permitted
• Suitable and interested to proceed to ASCT
• Measurable disease, prior to initial treatment as indicated by one or more of the following:
• Serum monoclonal (M)-protein \>= 0.5 g/dL
• Urine M-protein \>= 200 mg/24 hours
• If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable
• Life expectancy of more than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Bilirubin \< 1.5 times the upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 times ULN
• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L
• Hemoglobin \>= 8 g/dL
• Platelet count \>= 75 x 10\^9/L; subjects may receive red blood cell (RBC) transfusions or platelet transfusions, if clinically indicated in accordance with institutional guidelines; however, screening platelet count should be independent of platelet transfusions for at least 2 weeks

You may not qualify if:

• Non-secretory or hyposecretory multiple myeloma, prior to initial treatment defined as \< 0.5 g/dL M-protein in serum, \< 200 mg/24 hr urine M-protein, or disease only measured by serum free light chain
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Waldenstrom's macroglobulinemia or immunoglobin (Ig)M myeloma
• Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of protocol treatment (localized radiotherapy to a single site at least 1 week before start is permissible)
• Participation in an investigational therapeutic study within 3 weeks or within 5 drug half-lives (t1/2) prior to first dose, whichever time is greater
• Pregnant or lactating females
• History of allergy to mannitol
• Major surgery within 3 weeks prior to first dose
• Myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Uncontrolled hypertension or diabetes
• Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
• Known or suspected human immunodeficiency virus (HIV) infection, known HIV seropositivity
• Active hepatitis A, B, or C infection
• Non-hematologic malignancy within the past 3 years except adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer \< Gleason grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone
• Any clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Sponsors & Collaborators

• University of Chicago: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637-1470, United States

Location

Dana Farber

Boston, Massachusetts, 02215, United States

Location

Washington University in St Louis

St Louis, Missouri, 63130, United States

Location

Sarah Cannon Cancer Center

Nashville, Tennessee, 37203, United States

Location

Princess Margaret

Toronto, Ontario, M5T 2M9, Canada

Location

Related Publications (2)

• Landgren O, Kazandjian D, Roussel M, Jasielec J, Dytfeld D, Anderson A, Kervin TA, Iskander K, McFadden I, Jakubowiak AJ. Efficacy and safety of carfilzomib-lenalidomide-dexamethasone in newly diagnosed multiple myeloma: pooled analysis of four single-arm studies. Leuk Lymphoma. 2022 Oct;63(10):2413-2421. doi: 10.1080/10428194.2022.2068001. Epub 2022 May 12.

  PMID: 35549810 DERIVED

• Jasielec JK, Kubicki T, Raje N, Vij R, Reece D, Berdeja J, Derman BA, Rosenbaum CA, Richardson P, Gurbuxani S, Major S, Wolfe B, Stefka AT, Stephens L, Tinari KM, Hycner T, Rojek AE, Dytfeld D, Griffith KA, Zimmerman TM, Jakubowiak AJ. Carfilzomib, lenalidomide, and dexamethasone plus transplant in newly diagnosed multiple myeloma. Blood. 2020 Nov 26;136(22):2513-2523. doi: 10.1182/blood.2020007522.

  PMID: 32735641 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Dexamethasone; Calcium Dobesilate; carfilzomib; Lenalidomide

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)

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

Results Point of Contact

• Title: Andrzej Jakubowiak, MD, PhD
• Organization: University of Chicago Medical Center

ajakubowiak@medicine.bsd.uchicago.edu

773-702-4005

Study Officials

• Andrzej Jakubowiak

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2013
• First Posted: March 22, 2013
• Study Start: January 1, 2013
• Primary Completion: April 1, 2018
• Study Completion: March 30, 2026
• Last Updated: April 21, 2026
• Results First Posted: September 23, 2022

Record last verified: 2026-03

Locations

US (4); CA (1)