A Study of Carfilzomib, Lenalidomide, Vorinostat, and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma

NCT01297764 | Active Not Recruiting Phase 1 DMC

• 3 other identifiers: Pro00002074QUADRV-0549
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the feasibility of combining four of the most active agents available for the treatment of multiple myeloma. Further the investigators will attempt to assess the activity of this combination.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Safety and dose of carfilzomib, lenalidomide, vorinostat and dexamethasone for MM

  Primary Objective: To evaluate safety and establish the maximum tolerated dose (MTD) \[and/or a protocol defined dose below the MTD\] of carfilzomib, lenalidomide, vorinostat and dexamethasone in relapsed and/or refractory multiple myeloma subjects. Secondary Objectives: To observe evidence of efficacy (response rate, duration of response, time to progression, time to next treatment)

  Within 30 days of the last administration of study treatment

Secondary Outcomes (1)

• Overall response rate (ORR) Time to next treatment (TTNT) Time to progression (TTP) Duration of response (DOR

  Within 30 days of the last administration of study treatment

Study Arms (1)

carfilzomib for MML

EXPERIMENTAL

Vorinostat, Lenalidomide, Carfilzomib, Dexamethasone - This study will be conducted as an open-label Phase I/II, single-center study in which subjects will receive carfilzomib, lenalidomide, vorinostat and dexamethasone, for relapsed and/or refractory multiple myeloma. Study treatment will be administered in sequential cohorts, with 3-6 subjects in each cohort. Treatment will be administered in 28-day cycles, with the fourth week as a rest week, for 12 cycles or until disease progression or unacceptable toxicity develops.

Drug: Vorinostat, Lenalidomide, Carfilzomib, Dexamethasone

Interventions

Vorinostat, Lenalidomide, Carfilzomib, Dexamethasone DRUG

Dose Escalation Schema Cohort Carfilzomib (mg/m2) Lenalidomide (mg) Vorinostat (mg) Dexamethasone (mg) 1. 15 15 300 40 2. 20 15 300 40 3. 20 25 300 40 4. 20/27\* 25 300 40 5. 20/27\* 25 400 40

Also known as: Vorinostat (Zolinza), Lenalidomide (Revlimid), Carfilzomib (Kyprolis), Dexamethasone (Decadron, Baycadron)

carfilzomib for MML

Eligibility Criteria

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

You may qualify if:

• Disease related:
• Symptomatic multiple myeloma
• Relapsed and/or refractory multiple myeloma after at least one prior therapeutic regimen for multiple myeloma
• Prior treatment with immunomodulatory agents, proteasome inhibitors and histone deacetylase inhibitors is permitted. (Patients who have used HDAC inhibitors, including valproic acid , must have at least 5 half-lives wash out period before beginning therapy with vorinostat on this protocol.)
• Measurable disease, as indicated by one or more of the following:
• Serum M-protein ≥ 0.5 g/dL
• Urine Bence-Jones protein ≥ 200 mg/24 h
• If Serum Protein Electrophoresis is felt to be unreliable for routine M-protein measurement (particularly for patients with IgA MM), then quantitative immunoglobulin levels can be accepted.
• Serum free light chain ≥ 10 mg/dL (≥ 100 mg/L) and an abnormal free light chain ratio
• Demographic
• Males and females ≥ 18 years of age
• Life expectancy of more than three months
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 (see Appendix B)
• Laboratory
• Adequate hepatic function, with bilirubin \< 2 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) \< 3 times ULN 9.Absolute neutrophil count (ANC) ≥ 1,000/mm3 Hemoglobin ≥ 8 gm/dL Platelet count ≥ 50,000/ mm3 (≥ 30 × 109/L if myeloma involvement in the bone marrow is \> 50%)

You may not qualify if:

• Disease related
• Subjects with non-secretory or hyposecretory multiple myeloma, defined as \<0.5 g/dL M-protein in serum and \<200 mg/24 hr Bence Jones protein in urine and serum free light chain \<10mg/dL (\<100 mg/L) and no measurable plasmacytoma
• Corticosteroid therapy in a dose equivalent to dexamethasone ≥ 4 mg/day or prednisone ≥20 mg/day within 3 weeks prior to first dose
• Concurrent use of histone deacetylase inhibitor (eg. Valproic acid)
• Use of any other experimental drug or therapy within 28 days of baseline
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Waldenström's macroglobulinemia
• Chemotherapy with approved or investigative anticancer therapeutics, including steroid therapy dose as defined above, within 2 weeks prior to first dose
• Radiation therapy within 1 week prior to first dose, Immunotherapy within 3 weeks prior to first dose . Planned radiation therapy that occurs after the start of treatment
• 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.
• Concurrent conditions
• Pregnant or lactating females (Lactating females must agree not to breast feed while taking lenalidomide or vorinostat).
• History of allergy to boron or mannitol
• Major surgery within 2 weeks prior to first dose
• Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction in the previous six months

Sponsors & Collaborators

• Hackensack Meridian Health: lead

Study Sites (1)

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Related Publications (23)

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  BACKGROUND

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  BACKGROUND

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  PMID: 14695887 BACKGROUND

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  BACKGROUND

• Demo SD, Kirk CJ, Aujay MA, Buchholz TJ, Dajee M, Ho MN, Jiang J, Laidig GJ, Lewis ER, Parlati F, Shenk KD, Smyth MS, Sun CM, Vallone MK, Woo TM, Molineaux CJ, Bennett MK. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res. 2007 Jul 1;67(13):6383-91. doi: 10.1158/0008-5472.CAN-06-4086.

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MeSH Terms

Conditions

Multiple Myeloma

Interventions

Vorinostat; Lenalidomide; carfilzomib; 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)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Phthalimides; Phthalic Acids; Acids, Carbocyclic; 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

Study Officials

• David Siegel, MD, PhD

  Hackensack Meridian Health

  PRINCIPAL INVESTIGATOR

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: February 11, 2011
• First Posted: February 17, 2011
• Study Start: April 1, 2011
• Primary Completion: July 1, 2026
• Study Completion: July 1, 2026
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

US (1)