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Multiple MyelomaPhase 1/2QUADNCT01297764

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

A Phase 1/2 study testing Vorinostat, Lenalidomide, Carfilzomib, Dexamethasone in people with Multiple Myeloma, run by Hackensack Meridian Health at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Vorinostat, Lenalidomide, Carfilzomib, Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
Apr 2011to Jun 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must meet all of the following inclusion criteria to be eligible to enroll in this study:
  • 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:
Show all 22Show fewer
  • 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
  • 8.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%)
  • Screening ANC should be independent of granulocyte- and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G CSF for at least 2 weeks.
  • Subjects may receive red blood cell (RBC) or platelet transfusions, if clinically indicated, in accordance with institutional guidelines
  • Screening platelet count should be independent of platelet transfusions for at least 2 weeks 10.Calculated or measured creatinine clearance of ≥60 mL/minute, calculated using the formula of Cockcroft and Gault [(140 - Age) x Mass (kg) / (72 x creatinine mg/dL)]; multiply result by 0.85 (if female). Other generally accepted calculation methods can be substituted.11.Potassium level 3.5-5.2 meq/L (institutional normal range) Ethical/Other 12.Written informed consent in accordance with federal, local, and institutional guidelines 13.Females of Child Bearing Potential* (FCBP) must have a negative serum or urine pregnancy test, with a sensitivity of at least 50 mIU/mL within 10-14 days and again within 24 hours prior to prescribing lenalidomide for cycle 1 (prescription must be filled with 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO methods of acceptable methods of birth control, one highly effective method AND one additional effective method of birth control (contraception) AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy Testing. (See Appendix G: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods)
  • A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
  • 14. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy (See Appendix G: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods) 15. All study participants must be registered into the mandatory RevAssist® program and be willing and able to comply with the requirements of RevAssist®.
  • 16. Subjects must adhere to the study visit schedule and other protocol requirements and receive outpatient treatment and laboratory monitoring at the institute that administers the drug 17. Subjects must agree to take enteric-coated aspirin 81-325 mg orally daily, or if history of prior thrombotic disease or allergy to aspirin, must be fully anticoagulated with warfarin (INR 2-3) or be treated with full-dose, low molecular weight heparin, as if to treat deep venous thrombosis (DVT)/pulmonary embolism.

Who cannot join

  • Subjects who meet any of the following exclusion criteria are not eligible to be enrolled in this study:
  • 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
Show all 24Show fewer
  • 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
  • Uncontrolled hypertension
  • Acute active infection requiring intravenous antibiotics, antivirals, or antifungals within one week prior to first dose or oral antibiotics within 1 week
  • Known or suspected HIV infection, known HIV seropositivity, or active hepatitis A, B, or C infection.
  • Serious psychiatric or medical conditions that could interfere with treatment
  • Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose and/or within 14 days before enrollment
  • Contraindication to any of the required concomitant drugs, including proton-pump inhibitor (e.g., lansoprazole), antiviral agents, enteric-coated aspirin or other anticoagulant, or if a history of prior thrombotic disease, warfarin or low molecular weight heparin
  • Subjects in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment
  • Subjects with pleural effusions requiring therapeutic thoracentesis or ascites requiring therapeutic paracentesis

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

Other trials in United States

About this study

Official title: A Phase I/II Study of Carfilzomib, Lenalidomide, Vorinostat, and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma

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.

Read the detailed description

Phase I/II studies of the novel proteasome inhibitor, carfilzomib, have shown it to have significant activity in patients with advanced multiple myeloma, including patients with bortezomib refractory disease. This drug, unlike bortezomib, has minimal neurotoxicity and appears to have minimal gastrointestinal (GI) toxicity. Experience with the combination of bortezomib, lenalidomide and dexamethasone has shown both neuropathy and chronic diarrhea to be limiting.

Vorinostat is a histone deacetylase inhibitor with modest single agent activity in multiple myeloma. Dysesthesia, GI issues and fatigue have been problematic in this patient population. More recent studies combining vorinostat with lenalidomide and dexamethasone or with bortezomib have demonstrated a much more robust activity, including in patients refractory to lenalidomide or bortezomib-based combinations. Again, neuropathy, fatigue and GI issues have been problematic.

The investigators own anecdotal experience with combinations of proteasome inhibitor, histone deacetylase inhibitor, immunomodulators and dexamethasone has shown this combination to be extremely active and well tolerated. The combination of vorinostat, carfilzomib, lenalidomide and dexamethasone should offer the opportunity to maximize activity while limiting toxicities, particularly neuropathy and GI.

Being tested
Vorinostat, Lenalidomide, Carfilzomib, Dexamethasone
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vorinostat, Lenalidomide, Carfilzomib, DexamethasoneDrug

    Also called Vorinostat (Zolinza), Lenalidomide (Revlimid), Carfilzomib (Kyprolis), Dexamethasone (Decadron, Baycadron)

    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
Study groups in NCT01297764
Study groupRoleWhat they receive
carfilzomib for MMLExperimentalVorinostat, 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.
Receives: Drug: Vorinostat, Lenalidomide, Carfilzomib, Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: Within 30 days of the last administration of study treatment

Secondary outcomes (1)

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

    Secondary Objectives: To observe evidence of efficacy (response rate, duration of response, time to progression, time to next treatment)

    Measured: Within 30 days of the last administration of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2011 (estimated)
  2. Study startApr 2011
  3. Primary completionJun 2027 (estimated)
  4. Study completionJun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01297764
Sponsor's protocol ID
Pro00002074
Other IDs
QUAD, RV-0549
Acronym
QUAD
Status last verified
Aug 2026
First submitted
11 Feb 2011
Last updated
24 Aug 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • Ries LAG, Melbert D, Krapcho M, Mariotto A, Miller BA, Feuer EJ, et al (eds). SEER Cancer Statistics Review, 1975-2004, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2004/, based on November 2006 SEER data submission, posted to the SEER website, 2007.

  • Jawed I, Lee CM, Tward JD, Macdonald OK, Martincic D, Vudarla N, Fairbanks RK, et al. Survival outcomes for multiple myeloma over three decades: a surveillance, epidemiology, and end results (SEER) analysis. J Clin Oncol. 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007:8019.

  • Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, Siegel D, Borrello I, Rajkumar SV, Chanan-Khan AA, Lonial S, Yu Z, Patin J, Olesnyckyj M, Zeldis JB, Knight RD; Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007 Nov 22;357(21):2133-42. doi: 10.1056/NEJMoa070596.

    PubMed 18032763

  • Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foa R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD; Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007 Nov 22;357(21):2123-32. doi: 10.1056/NEJMoa070594.

    PubMed 18032762

  • Richardson PG, Jagannath S, Avigan DE, Alsina M, Schlossman RL, Mazumder A, et al. Lenalidomide plus bortezomib (Rev-Vel) in relapsed and/or refractory multiple myeloma (MM): final results of a multicenter phase 1 trial. Blood. 2006 Nov 16;108(11):Abstract #405.

  • Richardson P, Schlossman RL, Mitsiades CS, Munshi NC, Colson K, Doss D, et al. Phase I clinical trial of oral administration of the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) in patients with relapsed/refractory multiple myeloma (MM). [Abstract]. Blood 2004;104(11):420a.

  • Mitsiades N, Mitsiades CS, Richardson PG, McMullan C, Poulaki V, Fanourakis G, Schlossman R, Chauhan D, Munshi NC, Hideshima T, Richon VM, Marks PA, Anderson KC. Molecular sequelae of histone deacetylase inhibition in human malignant B cells. Blood. 2003 May 15;101(10):4055-62. doi: 10.1182/blood-2002-11-3514. Epub 2003 Jan 16.

    PubMed 12531799

  • Mitsiades CS, Mitsiades NS, McMullan CJ, Poulaki V, Shringarpure R, Hideshima T, Akiyama M, Chauhan D, Munshi N, Gu X, Bailey C, Joseph M, Libermann TA, Richon VM, Marks PA, Anderson KC. Transcriptional signature of histone deacetylase inhibition in multiple myeloma: biological and clinical implications. Proc Natl Acad Sci U S A. 2004 Jan 13;101(2):540-5. doi: 10.1073/pnas.2536759100. Epub 2003 Dec 26.

    PubMed 14695887

  • Siegel D, Weber DM, Mitsiades CS, Dimopoulo MA, Harousseau JL, Rizvi S, et al. Combined Vorinostat, Lenalidomide and Dexamethasone Therapy in Patients with Relapsed or Refractory Multiple Myeloma: A Phase I Study. [Abstract] Blood (ASH Annual Meeting Abstracts) 2009;114(22)304a.

  • Pei XY, Dai Y, Grant S. Synergistic induction of oxidative injury and apoptosis in human multiple myeloma cells by the proteasome inhibitor bortezomib and histone deacetylase inhibitors. Clin Cancer Res. 2004 Jun 1;10(11):3839-52. doi: 10.1158/1078-0432.CCR-03-0561.

    PubMed 15173093

  • Prince HM, Bishton M, Harrison S. The potential of histone deacetylase inhibitors for the treatment of multiple myeloma. Leuk Lymphoma. 2008 Mar;49(3):385-7. doi: 10.1080/10428190801950058.

    PubMed 18297514

  • Richardson PG, Mitsiades CS, Colson K, Reilly E, McBride L, Chiao J, et al. Final results of a phase I trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) in combination with bortezomib in patients with advanced multiple myeloma [Abstract]. Blood (ASH Annual Meeting Abstracts) 2007;110(11):1179.

  • Weber DM, Jagannath S, Mazumder A, Sobecks R, Schiller GJ, Gavino M, et al. Phase I trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) in combination with bortezomib in patients with advanced multiple myeloma [Abstract]. Blood (ASH Annual Meeting Abstracts) 2007;110(11):1172.

  • Weber D, Badros AZ, Jagannath S, Siegel D, Richon V, Rizvi S, Garcia-Vargas J, Reiser D and Anderson KC. Vorinostat Plus Bortezomib for the Treatment of Relapsed/Refractory Multiple Myeloma (MM): Early Clinical Experience. American Society of Hematology Annual Meeting Abstract Nov 2008;112:871.

  • Badros A, Philip S, Niesvizky R, Goloubeva O, Harris C, Zwiebel J, et al. Phase I trial of vorinostat (suberoylanilide hydroxamic acid, SAHA) plus bortezomib (Bort) in relapsed and refractory multiple myeloma (MM) patients (pts.). EHA (European Hematology Association annual Meeting Abstracts) 2008;93(s1)0642:258

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Vorinostat, Lenalidomide, Carfilzomib, Dexamethasone in people with Multiple Myeloma, run by Hackensack Meridian Health at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and dose of carfilzomib, lenalidomide, vorinostat and dexamethasone for MM (time frame: Within 30 days of the last administration of study treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01297764, which also lists 23 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.

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