Carfilzomib and Lenalidomide With Dexamethasone Combination in Newly Diagnosed, Previously Untreated Multiple Myeloma

NCT01029054 | Completed Phase 1 Results DMC

• 2 other identifiers: UMCC 2009.056HUM30396
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 4

Brief Summary

This study is designed to evaluate the safety and to determine the maximum tolerated dose of carfilzomib + lenalidomide in combination with dexamethasone in newly diagnosed Multiple Myeloma patients who have not received treatment.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• The Maximum Tolerated Dose (MTD) of Carfilzomib

  Determine the MTD of Carfilzomib when combined with Lenalidomide and Dexamethasone. The estimated time to determine the MTD is 6 months.

  6 Months

• The Percentage of Patients That Achieve a Response to Treatment

  The percentage of patients that achieve at least a sCR (Stringent Complete Response), at least a VGPR (Very Good Partial Response) and at least a PR (Partial Response) will be determined. sCR is defined as: * Negative immunofixation on the serum and urine and * Disappearance of any soft tissue plasmacytomas and * \< 5% plasma cells in bone marrow and * Normal SFLC ratio and * Absence of clonal cells in bone marrow VGPR is defined as: * Serum and urine M-protein detectable by immunofixation but not on electrophoresis or * ≥ 90% reduction in serum M-component with urine M-component \< 100 mg per 24 hours PR is defined as: * ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours * If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required

  4 Months After Treatment Start

Secondary Outcomes (1)

• The Percentage of Patients Alive Without Progression

  12 Months and 24 Months Post Treatment

Study Arms (1)

carfilzomib, lenalidomide w/dexamethasone

EXPERIMENTAL

Phase I: carfilzomib will be taken with a combination of lenalidomide plus dexamethasone in a series of escalating dosages to determine the maximum tolerated dose level Phase II: carfilzomib will be given at the MTD established in the Phase I portion of the study

Drug: carfilzomib, lenalidomide plus dexamethasone

Interventions

carfilzomib, lenalidomide plus dexamethasone DRUG

Phase I: Carfilzomib will be administered at the dosage assigned for the subject's cohort as an IV infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for Cycles 1 - 8 (induction) and on Days 1, 2, 15, and 16 of a 28-day cycle for Cycles 9+ (maintenance). Lenalidomide will be administered PO daily at 25 mg on Days 1- 21 of the 28-day cycle for Cycles 1 - 8+. Dexamethasone 40 mg will be administered PO or IV between 30 minutes and 4 hours preceding the carfilzomib push.

carfilzomib, lenalidomide w/dexamethasone

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed, histologically confirmed, previously untreated Stage I, II, or III multiple myeloma requiring systemic chemotherapy
• Diagnosis of symptomatic multiple myeloma per IMWG uniform criteria within the past 90 days
• Measurable disease, per IMWG (International Myeloma Working Group) criteria (\>= one of the following) within the past 4 weeks:
• Monoclonal protein \>= 0.5 g/dL by serum protein electrophoresis
• Monoclonal light chain \>= 200 mg by 24-hour urine protein electrophoresis
• If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable
• Life expectancy \> 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Adequate hepatic function, with bilirubin \< 1.5 x the ULN, and AST (Aspartate Aminotransferase) and ALT (Alanine Transaminase) \< 2.5 x ULN
• Absolute neutrophil count (ANC) \>=1.0 x 109/L, hemoglobin \>= 8 g/dL, platelet count \>= 75 x 109/L
• Calculated creatinine clearance (by Cockroft-Gault) \>= 60 ml/min
• Written informed consent in accordance with federal, local, and institutional guidelines.
• Subjects must agree to adhere to all study requirements, including birth control measures and pregnancy testing, visit schedule, outpatient treatment, required concomitant medications, and laboratory monitoring.
• Must be able to take either 81 mg or 325 mg aspirin daily as prophylactic anticoagulation.

You may not qualify if:

• Non-secretory or hyposecretory multiple myeloma, 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 (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes) syndrome
• Plasma cell leukemia
• Waldenström's macroglobulinemia or IgM myeloma
• Radiotherapy to multiple sites or immunotherapy within 2 weeks before start of protocol treatment (localized radiotherapy to a single site at least 1 week before start is permissible)
• Patient must not have been previously treated with any prior systemic therapy for the treatment of multiple myeloma
• Prior treatment of hypercalcemia or spinal cord compression or aggressively progressing myeloma with corticosteroids does not disqualify the patient (the dose should not exceed the equivalent of 160 mg of dexamethasone in a 2 week period)
• Bisphosphonates are permitted
• Participation in an investigational therapeutic study within 3 weeks or within 5 drug halflives (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 3 months prior to enrollment, NYHA (New York Heart Association) 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

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Onyx Therapeutics, Inc.: collaborator
• Celgene: collaborator

Study Sites (4)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Mt. Sinai Medical Center

New York, New York, 10029, United States

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

• Jakubowiak AJ, Dytfeld D, Griffith KA, Lebovic D, Vesole DH, Jagannath S, Al-Zoubi A, Anderson T, Nordgren B, Detweiler-Short K, Stockerl-Goldstein K, Ahmed A, Jobkar T, Durecki DE, McDonnell K, Mietzel M, Couriel D, Kaminski M, Vij R. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012 Aug 30;120(9):1801-9. doi: 10.1182/blood-2012-04-422683. Epub 2012 Jun 4.

  PMID: 22665938 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Lenalidomide; Dexamethasone

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

Results Point of Contact

• Title: Dr. Mark Kaminski, M.D.
• Organization: University of Michigan Hospital

mkaminsk@umich.edu

734-936-5310

Study Officials

• Mark Kaminski, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2009
• First Posted: December 9, 2009
• Study Start: September 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: July 1, 2015
• Last Updated: January 30, 2017
• Results First Posted: November 20, 2014

Record last verified: 2016-12

Locations

US (4)