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A Safety and Efficacy Study of Carfilzomib and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT01464034
Recruitment Status : Recruiting
First Posted : November 3, 2011
Last Update Posted : October 18, 2017
Sponsor:
Collaborators:
Amgen
Celgene Corporation
Information provided by (Responsible Party):
Criterium, Inc.

Tracking Information
First Submitted Date  ICMJE October 19, 2011
First Posted Date  ICMJE November 3, 2011
Last Update Posted Date October 18, 2017
Study Start Date  ICMJE November 2011
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 22, 2012)
  • Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Throughout treatment, estimated at 2-12 months per patient ]
    Review of adverse events for safety and to determine the maximum tolerated dose of the combination treatment.
  • Overall Response in Phase II [ Time Frame: Every 28 days while on treatment (estimated at 2- 12 months per patient) ]
    Overall Response (SD, MR, PR, VGPR, CR, sCR)
Original Primary Outcome Measures  ICMJE
 (submitted: November 2, 2011)
Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Throughout treatment, estimated at 2-12 months per patient ]
Review of adverse events for safety and to determine the maximum tolerated dose of the combination treatment.
Change History Complete list of historical versions of study NCT01464034 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 22, 2012)
  • Overall Response in Phase I [ Time Frame: Every 28 days while on treatment (estimated at 2- 12 months per patient) ]
    Overall response (SD, MR, PR, VGPR, CR, sCR)
  • Time to Progression [ Time Frame: Every 28 days while on treatment (estimated at 2-12 months per patient) ]
  • Progression Free Survival [ Time Frame: throughout follow up (every 2-3 months for 2 years) ]
  • Time to next therapy [ Time Frame: throughout follow up (every 2-3 months for 2 years) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2011)
  • Overall Response [ Time Frame: Every 28 days while on treatment (estimated at 2- 12 months per patient) ]
    Overall response (SD, MR, PR, VGPR, CR, sCR)
  • Time to Progression [ Time Frame: Every 28 days while on treatment (estimated at 2-12 months per patient) ]
  • Progression Free Survival [ Time Frame: throughout follow up (every 2-3 months for 2 years) ]
  • Time to next therapy [ Time Frame: throughout follow up (every 2-3 months for 2 years) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety and Efficacy Study of Carfilzomib and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Official Title  ICMJE A Multi-Center Phase I/II, Open-Label, Dose-Finding Pilot Study of the Combination of Carfilzomib and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Brief Summary This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated dose of the combination of carfilzomib and pomalidomide with dexamethasone (CPD) in patients with relapsed or refractory multiple myeloma followed by a phase II expansion at the MTD to evaluate efficacy.
Detailed Description This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated dose of the combination of carfilzomib and pomalidomide with dexamethasone (CPD) in patients with relapsed or refractory multiple myeloma followed by a phase II expansion at the MTD to evaluate efficacy. The study will explore the efficacy of CPD including overall response, time to progression, progression free survival, and time to next therapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Carfilzomib
    IV over 30 minutes on Days 1,2,8,9,15, and 16 every 28 days
    Other Name: PR-171
  • Drug: Pomalidomide
    PO daily on Days 1-21, every 28 Days
    Other Name: CC-4047
  • Drug: Dexamethasone
    40 mg weekly PO or IV on Days 1, 8, 15, and 22, every 28 days.
    Other Name: Decadron
Study Arms  ICMJE Experimental: Carfilzomib, Pomalidomide, Dexamethasone
All eligible subjects will receive the study intervention of Carfilzomib, Pomalidomide, and Dexamethasone.
Interventions:
  • Drug: Carfilzomib
  • Drug: Pomalidomide
  • Drug: Dexamethasone
Publications * Shah JJ, Stadtmauer EA, Abonour R, Cohen AD, Bensinger WI, Gasparetto C, Kaufman JL, Lentzsch S, Vogl DT, Gomes CL, Pascucci N, Smith DD, Orlowski RZ, Durie BG. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood. 2015 Nov 12;126(20):2284-90. doi: 10.1182/blood-2015-05-643320. Epub 2015 Sep 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 22, 2012)
117
Original Estimated Enrollment  ICMJE
 (submitted: November 2, 2011)
30
Estimated Study Completion Date  ICMJE June 2018
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Cytopathologically or histologically confirmed dx of multiple myeloma
  • Relapsed or refractory to the most recently received therapy.
  • All pts must have received prior lenalidomide therapy and been determined to be refractory, relapsed, or intolerant.
  • 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 hr Elevated Free Light Chain as per IMWG criteria, and abnormal ratio

  • Pts must be ≥ 18 years of age
  • Life expectancy of more than 3 months
  • ECOG PS of 0-2
  • Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times ULN
  • Uric acid must be within laboratory normal range
  • CrCl ≥ 50 mL/min
  • Additional Laboratory Requirements ANC ≥1.0 x 109/L Hgb ≥8 g/dL(transfusion permitted) Platelet count ≥50.0 x 109/L
  • 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
  • Pts may receive 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.
  • Written informed consent in accordance with federal, local, and institutional guidelines
  • FCBP must agree to ongoing pregnancy testing
  • FCBP must have a negative serum or urine pregnancy test and agree to birth control.
  • Male pts must agree to never have unprotected sexual contact with a female who can become pregnant and must agree to either completely abstain from sexual contact with females who are pregnant or are able to become pregnant. The patient must agree to inform his physician if he has had unprotected sexual contact with a female who can become pregnant or if he thinks for any reason that his sexual partner may be pregnant.
  • Male pts cannot donate semen or sperm while taking pomalidomide and for 28 days after completing the study.
  • All pts must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
  • Pts must agree to take enteric-coated aspirin 81 mg orally daily, or if history of prior thrombotic disease, 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 (PE)at the investigator's discretion

Exclusion Criteria:

  • Pts with known sensitivity to any immunomodulatory drugs (IMiDs)
  • Use of any other experimental drug or therapy within 21 days prior to first dose
  • Exposure to any prior chemotherapy, steroid use, or other myeloma treatment within 14 days prior to first dose. Pts currently on long term steroids do not require any washout period. in addition, steroid use for spinal cord compression is permitted and does not require a washout period.
  • Radiation therapy within 14 days prior to first dose
  • Known allergies to carfilzomib or Captisol
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Current diagnosis of plasma cell leukemia
  • Waldenström's macroglobulinemia
  • Major surgery within 21 days prior to first dose
  • Pregnant or lactating females
  • Congestive heart failure (NYHA class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction in the previous six months prior to first dose.
  • Uncontrolled hypertension
  • Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose
  • Pts receiving active treatment or intervention for any other malignancy or pts who, at the Investigator's discretion, may require active treatment or intervention for any other malignancy within 8 months of starting study treatment.
  • 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), enteric-coated aspirin or if a history of prior thrombotic disease, warfarin or low molecular weight heparin
  • Pts in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g. due to pre-existing pulmonary, cardiac, or renal impairment
  • Pts with primary systemic amyloidosis
  • Pts who have received prior treatment with carfilzomib (Phase II only)
  • Pts who have received prior treatment with pomalidomide (Phase II only)
  • Pts who have received prior treatment with both carfilzomib & pomalidomide (Phase I only)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01464034
Other Study ID Numbers  ICMJE AMyC 10-MM-01
IST-CAR-521 ( Other Identifier: Onyx Pharmaceuticals )
PO-MM-PI-0034 ( Other Identifier: Celgene Corporation )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Criterium, Inc.
Study Sponsor  ICMJE Criterium, Inc.
Collaborators  ICMJE
  • Amgen
  • Celgene Corporation
Investigators  ICMJE
Principal Investigator: Jatin Shah, MD AMyC
Principal Investigator: Brian GM Durie, MD AMyC
PRS Account Criterium, Inc.
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP