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High-Dose Weekly Carfilzomib Plus Cyclophosphamide and Dexamethasone in the Treatment of Relapsed Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT02597062
Recruitment Status : Active, not recruiting
First Posted : November 4, 2015
Last Update Posted : January 29, 2018
Myeloma Canada Research Network
Information provided by (Responsible Party):
Canadian Cancer Trials Group

Brief Summary:
The purpose of this study is to find out what effects carfilzomib has on relapsed multiple myeloma when administered in combination with cyclophosphamide and dexamethasone.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Carfilzomib Drug: Cyclophosphamide Drug: Dexamethasone Phase 2

Detailed Description:

Multiple Myeloma is a cancer that affects the bone marrow where the cells in our blood system are formed. This includes the white cells, red cells, platelets and lymphoid cells. In multiple myeloma the plasma cell (one of the lymphoid cells) starts to reproduce out of control. This results in crowding of the bone marrow with abnormal production of all the cells and a malfunction of the plasma cells. They can also cause damage to the normal bone resulting in pain, fractures and other complications.

The standard or usual treatments for your disease are lenalidomide (an immunomodulatory drug) or bortezomib (a proteasome inhibitor) based treatments.

Carfilzomib is a new type of proteasome inhibitor that is approved for the treatment of relapsed multiple myeloma in the United States.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm Phase II Study of High-Dose Weekly Carfilzomib Plus Cyclophosphamide and Dexamethasone in the Treatment of Relapsed Multiple Myeloma After 1-3 Prior Therapies
Study Start Date : March 29, 2016
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : December 2022

Arm Intervention/treatment
Experimental: Carfilzomib plus cyclophosphamide plus dexamethasone
20 mg/m2 day 1 of first cycle then escalated to 70 mg/m2 for all subsequent doses) given on days 1, 8, and 15 of a 28 day cycle plus weekly oral dexamethasone (< 70 years, 40 mg; ≥ 70 years 20mg) and cyclophosphamide 300 mg/m2 capped at 500 mg
Drug: Carfilzomib Drug: Cyclophosphamide Drug: Dexamethasone

Primary Outcome Measures :
  1. Overall response rate after 4 cycles [ Time Frame: 4 months ]

Secondary Outcome Measures :
  1. Number and severity of adverse events [ Time Frame: 3 years ]
  2. Response rates assessed by current International Myeloma Working Group (IMWG) criteria. [ Time Frame: 3 years ]
  3. Progression-free survival assessed by biochemistry, radiology and immunology tests [ Time Frame: 3 years ]
  4. Overall survival [ Time Frame: 2 years ]

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Relapsed symptomatic multiple myeloma as per the International Myeloma Working group criteria [Palumbo 2009].
  • Measurable disease, as defined by one or more of the following (assessed within 21 days prior to registration):

    • Serum M-protein ≥ 5 g/L (0.5g/dL)
    • Urine Bence-Jones protein ≥ 200 mg/24 hours
    • Involved serum free light chain (FLC) measurement ≥ 100 mg/L (10 mg/dL), provided serum FLC ratio is abnormal (abnormal if FLC ratio is <0.26 or >1.65)
    • Biopsy proven plasmacytoma
    • For IgA patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) ≥ 750 mg/dL (0.75 g/dL)
  • Prior treatment with at least one, but no more than three, regimens for multiple myeloma
  • Documented relapse or progressive disease on or after any regimen (subjects refractory to the most recent line of therapy are eligible except those who are refractory to bortezomib and cyclophosphamide as described in exclusion criteria 1.
  • Achieved a response to at least one prior regimen (defined as ≥ 25% decrease in M-protein)
  • Age ≥ 18 years.
  • Life expectancy ≥ 3 months.
  • ECOG performance status 0-2.
  • Laboratory Requirements (must be done within 21 days of registration):
  • Hematology:

    • Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
    • Hemoglobin ≥ 8 g/dL (80 g/L) (subjects may be receiving red blood cell (RBC) transfusions in accordance with institutional guidelines)
    • Platelet count ≥ 50 × 10^9/L, independent of platelet transfusions for 7 days. (≥ 30 × 10^9/L if myeloma involvement in the bone marrow is ≥ 50%)
  • Biochemistry:

    • ALT ≤ 3.5 x UNL
    • Serum direct bilirubin ≤ 2 mg/dL (34 μmol/L) (only required if total bilirubin ≥ 2mg/dL (34μmol/L)
    • Creatinine clearance (CrCl) ≥ 30 mL/minute (Crockcroft and Gault formula) and not on dialysis.
  • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
  • Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre.
  • In accordance with CRO policy, protocol treatment is to begin within 2 working days of patient registration.
  • Women/men of childbearing potential must have agreed to use a highly effective contraceptive method.

Exclusion Criteria:

  • Refractory to any proteasome inhibitor therapy (bortezomib, ixazomib, etc.) Refractory disease is defined as failure to respond to the proteasome inhibitor, initial response followed by progression while on a proteasome inhibitor, or relapse within 60 days of stopping proteasome inhibitor therapy.
  • Prior carfilzomib treatment.
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Waldenström's macroglobulinemia or IgM myeloma
  • Current or previous Plasma cell leukemia defined as (> 2.0 × 10^9/L circulating plasma cells by standard differential)
  • Chemotherapy or investigational agent within 3 weeks prior to registration or antibody therapy within 6 weeks prior to registration
  • Radiotherapy to multiple sites within 28 days prior to registration; localized radiotherapy to a single site within 7 days prior to registration
  • Plasmapheresisis within 14 days of registration.
  • Pregnant or lactating females.
  • Major surgery within 21 days prior to registration.
  • Active, uncontrolled bacterial, fungal, or viral infection.
  • Concurrent amyloidosis
  • Known human immunodeficiency virus infection.
  • Active hepatitis B or C infection.
  • Myocardial infarction within 4 months prior to registration, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker.
  • Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to registration.
  • Other malignancy, including MDS, within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; carcinoma in situ of the cervix or breast; prostate cancer of Gleason Score 6 or less with stable prostate-specific antigen levels; or cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumours of the adrenal or pancreas.
  • Significant neuropathy (≥ grade 3, or grade 2 with pain) within 14 days prior to registration.
  • Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib).
  • Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment.
  • Ongoing graft-versus-host disease.
  • Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to registration.
  • Any other 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.

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): NCT02597062

Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, New Brunswick
Regional Health Authority B, Zone 2
Saint John, New Brunswick, Canada, E2L 4L2
Canada, Nova Scotia
QEII Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Kingston Health Sciences Centre
Kingston, Ontario, Canada, K7L 2V7
London Regional Cancer Program
London, Ontario, Canada, N6A 5W9
Ottawa Hospital Research Institute
Ottawa, Ontario, Canada, K1H 8L6
University Health Network
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
CIUSSS de l'Est-de-I'lle-de-Montreal
Montreal, Quebec, Canada, H1T 2M4
CHUQ-Pavillon Hotel-Dieu de Quebec
Quebec City, Quebec, Canada, G1R 2J6
Sponsors and Collaborators
Canadian Cancer Trials Group
Myeloma Canada Research Network
Study Chair: Christopher Venner Cross Cancer Institute, Edmonton Alberta Canada

Responsible Party: Canadian Cancer Trials Group
ClinicalTrials.gov Identifier: NCT02597062     History of Changes
Other Study ID Numbers: MYX1
MCRN003 ( Other Identifier: MCRN )
First Posted: November 4, 2015    Key Record Dates
Last Update Posted: January 29, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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