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Multiple MyelomaPhase 2NCT02597062

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

A Phase 2 study testing Carfilzomib, Cyclophosphamide and Dexamethasone in people with Multiple Myeloma, run by Canadian Cancer Trials Group at 9 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. 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?
Carfilzomib, Cyclophosphamide and Dexamethasone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
76 participants
Where
9 sitesCanada
Study dates
5 Jul 2016to 1 Feb 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • 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
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  • 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.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Canada9 sites

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • QEII Health Sciences Centre

    Halifax, Nova Scotia, B3H 1V7

  • Kingston Health Sciences Centre

    Kingston, Ontario, K7L 2V7

  • London Regional Cancer Program

    London, Ontario, N6A 5W9

  • CIUSSS de l'Est-de-I'lle-de-Montreal

    Montreal, Quebec, H1T 2M4

  • Ottawa Hospital Research Institute

    Ottawa, Ontario, K1H 8L6

  • CHUQ-Pavillon Hotel-Dieu de Quebec

    Québec, Quebec, G1R 2J6

  • Regional Health Authority B, Zone 2

    Saint John, New Brunswick, E2L 4L2

  • University Health Network

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

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

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.

Read the 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.

Medical subject headings
Multiple Myeloma

What participants receive

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

Study groups in NCT02597062
Study groupRoleWhat they receive
Carfilzomib plus cyclophosphamide plus dexamethasoneExperimental20 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
Receives: Drug: Carfilzomib; Drug: Cyclophosphamide; Drug: Dexamethasone

What is being measured

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

  1. Overall Response Rate After 4 Cycles

    Response rate to protocol treatment after 4 cycles is define by stringent complete response, complete response, partial response, very good partial response, minimal response.

    Complete response: Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow biopsy Stringent complete response: Complete response plus Absence of clonal cells in bone marrow d by immunohistochemistry or immunofluorescence Very good partial response: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein with urine M-protein level <100 mg/24 hours.

    Partial response: ≥50% reduction in serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours Minimal response: 25-49% reduction in serum M-protein, and 50-89% reduction in 24-hour urinary M-protein, if ≥ 200 mg/24 hours at baseline

    Measured: 4 months

Secondary outcomes (2)

  1. Progression-free Survival

    Median time to progression or death assessed by biochemistry, radiology and immunology tests will be reported. Progression is evaluated in this study using the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) with any one or more of the following:

    1. Increase of ≥ 25% from lowest response value in: Serum M-component and/or Urine M-component and/or Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels or Bone marrow plasma cell percentages.
    2. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas
    3. Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL (0.115 g/L) or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.

    Measured: 3 years

  2. Overall Survival

    Median time to death in months will be reported

    Measured: 3 years

Timeline

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

  1. First posted4 Nov 2015 (estimated)
  2. Study start5 Jul 2016
  3. Primary completion19 Jun 2019
  4. Study completion1 Feb 2022

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
76 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02597062
Sponsor's protocol ID
MYX1
Other IDs
MCRN003
Status last verified
Feb 2022
First submitted
3 Nov 2015
Last updated
28 Aug 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Venner CP, LeBlanc R, Sandhu I, White D, Belch AR, Reece DE, Chen C, Dolan S, Lalancette M, Louzada M, Kew A, McCurdy A, Monteith B, Reiman T, McDonald G, Sherry M, Gul E, Chen BE, Hay AE. Weekly carfilzomib plus cyclophosphamide and dexamethasone in the treatment of relapsed/refractory multiple myeloma: Final results from the MCRN-003/MYX.1 single arm phase II trial. Am J Hematol. 2021 May 1;96(5):552-560. doi: 10.1002/ajh.26147.

    PubMed 33650179

  • Monteith BE, Venner CP, Reece DE, Kew AK, Lalancette M, Garland JS, Shepherd LE, Pater JL, Hay AE. Drug-induced Thrombotic Microangiopathy with Concurrent Proteasome Inhibitor Use in the Treatment of Multiple Myeloma: A Case Series and Review of the Literature. Clin Lymphoma Myeloma Leuk. 2020 Nov;20(11):e791-e800. doi: 10.1016/j.clml.2020.04.014. Epub 2020 Apr 30.

    PubMed 32807717

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carfilzomib, Cyclophosphamide and Dexamethasone in people with Multiple Myeloma, run by Canadian Cancer Trials Group at 9 sites in Canada.

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 26 inclusion and 23 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: finished, as of the sponsor's last update on 28 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Canada. 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 phase mean?

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?

Yes. Results are posted in the registry (first posted 3 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Overall Response Rate After 4 Cycles (time frame: 4 months). 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 NCT02597062, which also lists 2 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 28 Aug 2023.

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