ClinicalTrials.gov
ClinicalTrials.gov Menu

Carfilzomib, Pomalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01665794
Recruitment Status : Recruiting
First Posted : August 15, 2012
Last Update Posted : April 3, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Multiple Myeloma Research Foundation
Information provided by (Responsible Party):
University of Chicago

Brief Summary:

The study will investigate the effects of adding carfilzomib to the combination of pomalidomide and dexamethasone in sequential dose escalation cohorts in patients with relapsed or refractory multiple myeloma. This portion of the study is complete.

This study will also investigate the effects of adding daratumumab to the combination of carfilzomib, pomalidomide and dexamethasone.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Pomalidomide Drug: Carfilzomib Drug: dexamethasone Drug: Daratumumab Phase 1 Phase 2

Detailed Description:
Patients receive carfilzomib, pomalidomide, and dexamethasone in 28 days treatment cycles. Study treatment continues for as long a their myeloma does not worsen and they do not have unacceptable side effects. After completion of study treatment, patients are followed for up to 2 years.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 101 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Open-label, Single-arm, Phase 1b/2 Study of the Safety and Efficacy of Combination Treatment With Pomalidomide, Dexamethasone, and Carfilzomib (PdC) in Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma
Actual Study Start Date : August 13, 2012
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Experimental: PdC Group
Patients receive carfilzomib, pomalidomide, and dexamethasone at indicated doses and schedule every 28 days. Patients may continue to receive treatment in the absence of disease progression or unacceptable toxicity.
Drug: Pomalidomide
Pomalidomide taken orally at assigned dose.
Other Names:
  • CC-4047
  • Pomalyst(R)

Drug: Carfilzomib
Carfilzomib given by intravenous (IV) infusion at assigned dose.
Other Names:
  • Kyprolis (R)
  • PR-171

Drug: dexamethasone
Dexamethasone taken orally of given by IV infusion.
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM

Experimental: PdC + Dara Group
Patients receive carfilzomib, pomalidomide, dexamethasone, and daratumumab at indicated doses and schedule every 28 days. Patients may continue to receive treatment in the absence of disease progression or unacceptable toxicity.
Drug: Pomalidomide
Pomalidomide taken orally at assigned dose.
Other Names:
  • CC-4047
  • Pomalyst(R)

Drug: Carfilzomib
Carfilzomib given by intravenous (IV) infusion at assigned dose.
Other Names:
  • Kyprolis (R)
  • PR-171

Drug: dexamethasone
Dexamethasone taken orally of given by IV infusion.
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM

Drug: Daratumumab
Daratumumab given by intravenous (IV) infusion at assigned dose.
Other Name: Daralex




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of carfilzomib when administered in combination with pomalidomide and dexamethasone [ Time Frame: 28 days ]
  2. Partial response rate after 4 courses according to International Myeloma Working Group (IMWG) criteria [ Time Frame: 4 months ]
    The proportion and exact 95% binomial confidence interval for the response rate will be reported adjusted for the two-stage design of this trial.

  3. Response rates of carfilzomib, pomalidomide, dexamethasone, and daratumumab dosing according to International Myeloma Working Group (IMWG) criteria [ Time Frame: 4 months ]

Secondary Outcome Measures :
  1. Overall response rate [ Time Frame: Up to 2 years ]
    Defined as at least a partial response to therapy, will be reported along with its exact 95% binomial confidence

  2. Time to progression [ Time Frame: Up to 2 years ]
    Estimated using the product-limit method of Kaplan and Meier.

  3. Duration of response [ Time Frame: From the date of the clinical examination which confirmed the response, until the date of disease progression, or censoring at the date of last clinical follow-up up to 2 years ]
    Assessed conditional upon achieving at least a partial response.

  4. Progression-free survival [ Time Frame: From the date of first therapy until the date of documented disease progression or death up to 2 years ]
    Estimated using the product-limit method of Kaplan and Meier.

  5. Overall survival [ Time Frame: Up to 2 years ]
    Estimated using the product-limit method of Kaplan and Meier.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Relapsed and relapsed/refractory multiple myeloma requiring systemic therapy
  • Failed at least one prior treatment for multiple myeloma (must have received lenalidomide)

    • To be enrolled as second line therapy: Must be refractory to lenalidomide (progression on therapy or within 60 days of lenalidomide dosing)
  • Measurable disease, as indicated by one or more of the following:

    • Serum M-protein >= 0.5 g/dL
    • Urine M-protein >= 200 mg/24 hours
    • If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable
    • Involved serum free light chains ≥ 10 mg/dL (free light change ratio must be abnormal)
  • Aged 18 years or older
  • Life expectancy of more than 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Adequate Liver Function

    • Bilirubin < 1.5 times the upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) < 2.5 times ULN
    • Alanine aminotransferase (ALT) < 2.5 times ULN
  • Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
  • Hemoglobin >= 8 g/dL
  • Platelet count >= 75 x 10^9/L (should be independent of platelet transfusions for at least 2 weeks)
  • Calculated or measured creatinine clearance of >= 30 mL/minute
  • Written informed consent
  • Negative pregnancy test (for women of childbearing potential) within 10-14 days of starting study treatment and again within 24 hours of first pomalidomide dose
  • Must agree to practice abstinence or use two acceptable methods of birth control
  • Men must agree to use latex condom during sexual contact with women of childbearing potential (even if post vasectomy)
  • Must agree to adhere to all study requirements, visit schedule, outpatient treatment, required concomitant medications, and laboratory monitoring
  • Must register to mandatory POMALYST REMS™ program and be willing and able to comply with the requirements of the POMALYST REMS™ program

Exclusion Criteria:

  • Patients for whom there is the prospect of stem cell transplantation in the next 6 months in the treatment plan are excluded
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Plasma cell leukemia
  • Waldenström's macroglobulinemia or immunoglobulin M (IgM) myeloma
  • Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of protocol treatment (localized radiotherapy to a single site at least 1 week before start is permissible)
  • 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
  • Patients known to be refractory to any proteasome inhibitor other than bortezomib or carfilzomib
  • Pregnant or lactating
  • History of allergy to mannitol or prior hypersensitivity to thalidomide, lenalidomide or pomalidomide
  • Major surgery within 3 weeks prior to first dose,
  • Prior peripheral stem cell transplant within 12 weeks of study enrollment
  • Has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal (with the exception of hormones for thyroid conditions or estrogen replacement therapy [ERT]), or any investigational therapy within 21 days of enrollment
  • Myocardial infarction within 6 months prior to enrollment, New York Heart Associate (NYHA) 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 anti fungals within two weeks prior to first dose
  • Known or suspected human immunodeficiency (HIV) infection, known HIV seropositivity
  • Active hepatitis A, B, or C infection
  • Non-hematologic malignancy within the past 3 years except adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix or breast, prostate cancer < Gleason grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone
  • Any clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
  • Significant neuropathy (grades 3-4, or grade 2 with pain) at the time of the first dose and/or within 14 days before enrollment
  • Contraindications to any of the required concomitant drugs, including proton-pump inhibitor (eg, lansoprazole), enteric-coated aspirin, allopurinol or if a history of prior thrombotic disease, warfarin or low molecular weight heparin
  • Subjects in whom the required program of PO and IV fluid hydration is contraindicated, eg, due to pre-existing pulmonary, cardiac, or renal impairment
  • Subjects with known or suspected amyloidosis of any organ
  • Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis
  • Prior exposure to daratumumab

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01665794


Locations
United States, Illinois
University of Chicago Comprehensive Cancer Center Recruiting
Chicago, Illinois, United States, 60637-1470
Contact: Andrzej J. Jakubowiak    773-834-1592    ajakubowiak@medicine.bsd.uchicago.edu   
Principal Investigator: Andrzej J. Jakubowiak         
United States, Michigan
University of Michigan Comprehensive Cancer Center Active, not recruiting
Ann Arbor, Michigan, United States, 48109
Wayne State University - Karmonos Cancer Center Active, not recruiting
Detroit, Michigan, United States, 48201
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Jesus Berdeja, MD    615-329-7274      
Canada, Ontario
University Health Network - Princess Margaret Cancer Center Active, not recruiting
Toronto, Ontario, Canada, MISG 2M9
Sponsors and Collaborators
University of Chicago
National Cancer Institute (NCI)
Multiple Myeloma Research Foundation
Investigators
Principal Investigator: Andrzej Jakubowiak University of Chicago Comprehensive Cancer Center

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT01665794     History of Changes
Other Study ID Numbers: 12-1088
NCI-2012-01168 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: August 15, 2012    Key Record Dates
Last Update Posted: April 3, 2018
Last Verified: March 2018

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Pomalidomide
Daratumumab
Thalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal