High Dose Carfilzomib for Newly Diagnosed Myeloma

NCT02937571 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 15-326
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to test whether giving high doses of carfilzomib along with the other drugs (lenalidomide and dexamethasone) is safe and which dose is best tolerated by patients. In addition, the study is designed to test the amount of remaining myeloma cells in the body after treatment with higher carfilzomib doses which is known as minimal residual disease (MRD).

Conditions

Multiple Myeloma

Keywords

Carfilzomib; Lenalidomide; Dexamethasone; 15-326

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Dose Limiting Toxicity

  To find the maximum tolerated dose.A DLT is defined as any of the below toxicities with attribution to one or more of the study drugs that occur during Cycle 1. All AEs should be considered relevant to determining dose-limiting toxicities and to reporting unless the event can clearly be determined to be UNRELATED to the drug. NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.

  Cycle 1, up to 28 days

Study Arms (1)

Carfilzomib, Lenalidomide, and Dexamethasone

EXPERIMENTAL

* Cycle 1 ONLY: Carfilzomib 20 mg/m2 per dose, days 1 and 2; Carfilzomib 45 or 56 mg/m2 per dose, days 8, 9, 15, and 16. * Cycles 2- up to 12: Carfilzomib 45 or 56 mg/m2 per dose, days 1, 2, 8, 9, 15, and 16 * Cycles 1- up to 12: Lenalidomide 25 mg/day, days 1-21 every 28 days * Cycles 1-4: Dexamethasone 20 mg/dose, days 1, 2, 8, 9, 15, 16, 22, and 23 * Cycles 5- up to 12: Dexamethasone 10 mg/dose, days 1, 2, 8, 9, 15, 16, 22 and 23

Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Carfilzomib, Lenalidomide, and Dexamethasone

Lenalidomide DRUG

Carfilzomib, Lenalidomide, and Dexamethasone

Dexamethasone DRUG

Carfilzomib, Lenalidomide, and 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 patients with histologically confirmed MM based on the following criteria:
• Clonal plasma cells in the bone marrow
• Measurable disease within the past 4 weeks defined by any one of the following:
• Serum monoclonal protein ≥ 1.0 g/dL
• Urine monoclonal protein \>200 mg/24 hour
• Involved serum immunoglobulin free light chain \> 10 mg/dL AND abnormal kappa/lambda ratio
• Evidence of underlying end organ damage and/or myeloma defining event attributed to underlying plasma cell proliferative disorder meeting at least one of the following:
• Hypercalcemia: serum calcium \>0.25 mmol/L (\> 1 mg/dL) above upper limit of normal or ≥ 2.75 mmol/L (11 mg/dL)
• Anemia: hemoglobin value \<10 g/dL or \> 2 g/dL below lower limit of normal
• Bone disease: ≥ 1 lytic lesions on skeletal X-ray, CT, or PET-CT. For patients with 1 lytic lesion, bone marrow should demonstrate ≥10% clonal plasma cells
• Clonal bone marrow plasma cell percentage ≥60%
• Involved/un-involved serum free light chain ratio ≥100 and involved free light chain \>100 mg/L.
• focal lesion on magnetic resonance imaging study (lesion must be \>5 mm) in size
• Creatinine Clearance ≥ 60 ml/min. CrCl can be measured or estimated using Cockcroft-Gault method
• Age ≥ 18 years at the time of signing the informed consent documentation

You may not qualify if:

• Patients receiving \>1 cycle of prior treatment or concurrent systemic treatment for multiple myeloma.
• Treatment of hypercalcemia or spinal cord compression or aggressively progressing myeloma with current or prior corticosteroids is permitted
• Bisphosphonates are permitted
• Concurrent or prior treatment with corticosteroids for indications other than multiple myeloma is permitted
• Prior treatment with radiotherapy is permitted
• Prior treatment for smoldering myeloma is permitted with a washout period of 4 weeks from last dose. Smoldering patients previously treated with carfilzomib are excluded.
• Patients with measurable disease who received up to one cycle of any therapy within 60 days with a washout period of 4 weeks from last dose (on a trial or outside a trial) are eligible
• Plasma cell leukemia
• POEMS syndrome
• Amyloidosis
• Pregnant or lactating females. Because there is a potential risk for adverse events nursing infants secondary to treatment of the mother with carfilzomib in combination with lenalidomide. These potential risks may also apply to other agents used in this study.
• Uncontrolled hypertension or diabetes
• Active hepatitis B or C infection
• Known or suspected HIV or serologically positive
• Has significant cardiovascular disease with NYHA Class III or IV symptoms, EF\<40% or hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction within 6 months prior to enrollment, or unstable angina, or unstable arrhythmia as determined by history and physical examination. Echocardiogram will be performed during screening evaluation.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Onyx/Amgen: collaborator
• Celgene: collaborator

Study Sites (6)

Memorial Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

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. Neha Korde, MD
• Organization: Memorial Sloan Kettering Cancer Center

korden@mskcc.org

646-608-3708

Study Officials

• Neha Korde, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: October 17, 2016
• First Posted: October 18, 2016
• Study Start: October 1, 2016
• Primary Completion: October 8, 2024
• Study Completion: October 8, 2024
• Last Updated: November 20, 2025
• Results First Posted: November 20, 2025

Record last verified: 2024-10

Locations

US (6)