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

This study is currently recruiting participants.
Verified March 2017 by Canadian Cancer Trials Group
Sponsor:
ClinicalTrials.gov Identifier:
NCT02597062
First Posted: November 4, 2015
Last Update Posted: July 13, 2017
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.
Collaborators:
Amgen
Myeloma Canada Research Network
Information provided by (Responsible Party):
Canadian Cancer Trials Group
  Purpose
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 Intervention Phase
Multiple Myeloma Drug: Carfilzomib Drug: Cyclophosphamide Drug: Dexamethasone Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Canadian Cancer Trials Group:

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

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

Estimated Enrollment: 76
Study Start Date: March 29, 2016
Estimated Study Completion Date: December 2022
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 40 mg and cyclophosphamide 300 mg/m2 capped at 500 mg
Drug: Carfilzomib Drug: Cyclophosphamide Drug: Dexamethasone

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.

  Eligibility

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, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  • Bortezomib (alone or in combination) refractory disease defined as patients who do not respond to bortezomib, who initially respond and then progress while on bortezomib, or patients who relapse within 60 days of stopping bortezomib.
  • 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.
  • Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to registration.
  • 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.
  Contacts and Locations
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


Contacts
Contact: Annette Hay 613-533-6430 ahay@ctg.queensu.ca

Locations
Canada, Alberta
Cross Cancer Institute Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Christopher Venner    780 432-8757      
Canada, New Brunswick
Regional Health Authority B, Zone 2 Recruiting
Saint John, New Brunswick, Canada, E2L 4L2
Contact: Anthony J. Reiman    506 648-6884      
Canada, Nova Scotia
QEII Health Sciences Centre Recruiting
Halifax, Nova Scotia, Canada, B3H 1V7
Contact: Darrell White    902 473-4642      
Canada, Ontario
Cancer Centre of Southeastern Ontario at Kingston Recruiting
Kingston, Ontario, Canada, K7L 5P9
Contact: Annette Hay    613 533-6430 ext 77094      
London Regional Cancer Program Recruiting
London, Ontario, Canada, N6A 5W9
Contact: Martha Louzada    519 685-2391      
Ottawa Hospital Research Institute Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Andrea K. Kew         
University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Donna E. Reece    416 946-2994      
Canada, Quebec
CIUSSS de l'Est-de-I'lle-de-Montreal Recruiting
Montreal, Quebec, Canada, H1T 2M4
Contact: Richard LeBlanc    514 252-3400 ext 3404      
CHUQ-Pavillon Hotel-Dieu de Quebec Recruiting
Quebec City, Quebec, Canada, G1R 2J6
Contact: Marc Lalancette    418 691-5225      
Sponsors and Collaborators
Canadian Cancer Trials Group
Amgen
Myeloma Canada Research Network
Investigators
Study Chair: Christopher Venner Cross Cancer Institute, Edmonton Alberta Canada
  More Information

Responsible Party: Canadian Cancer Trials Group
ClinicalTrials.gov Identifier: NCT02597062     History of Changes
Other Study ID Numbers: MYX1
MCRN003 ( Other Identifier: MCRN )
First Submitted: November 3, 2015
First Posted: November 4, 2015
Last Update Posted: July 13, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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
Cyclophosphamide
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
Antineoplastic Agents
Protease Inhibitors