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Multiple MyelomaPhase 1/2wCCydNCT01857115

Study of Weekly Carfilzomib, Cyclophosphamide and Dexamethasone In Newly Diagnosed Multiple Myeloma Patients (wCCyd)

A Phase 1/2 study testing Carfilzomib, Cyclophosphamide and Dexamethasone in people with Multiple Myeloma, run by European Myeloma Network B.V. at 1 site in Italy.

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

This protocol is a phase I/II multicenter study designed to assess the safety and the efficacy of the proposed combinations as up-front treatment in elderly Multiple Myeloma (MM) patients. Read more about this study

Who is it for?
Ages 65 to 99 years
Conditions the study is for
Multiple Myeloma
What is being tested?
Carfilzomib, Cyclophosphamide and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
63 participants
Where
1 siteItaly
Study dates
Apr 2013to 1 Sep 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

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 65 to 99 years
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • Disease-related
  • Patient is a newly diagnosed MM patient.
  • Patient is age ≥ 65 year of age or who are ineligible for autologous stem cell transplantation.
  • Patient has measurable disease, defined as follows: any quantifiable serum monoclonal protein value (generally, but not necessarily, ≥ 0.5 g/dL of M-protein) and, where applicable, urine light-chain excretion of > 200 mg/24 hours. For patients with oligo- or non-secretory MM, it is required that they have measurable plasmacytoma > 2 cm as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or an abnormal free light chain ratio (n.v.: 0.26-1.65). We anticipate that less than 10% of patients admitted to this study will be oligo- or non-secretory MM with free light chains only in order to maximize interpretation of benefit results.
  • Demographic:
  • Age ≥ 18 years.
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  • Life expectancy ≥ 3 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix F).
  • Laboratory:
  • Adequate hepatic function, with serum ALT ≤ 3.5 times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 14 days prior to randomization.
  • Absolute neutrophil count (ANC) ≥ 1.0 × 109/L within 14 days prior to randomization.
  • Corrected serum calcium ≤ 14 mg/dL (3.5 mmol/L).
  • Alanine transaminase (ALT): ≤ 3 x the ULN.
  • Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to randomization (subjects may be receiving red blood cell [RBC] transfusions in accordance with institutional guidelines).
  • Platelet count ≥ 50 × 109/L (≥ 30 × 109/L if myeloma involvement in the bone marrow is > 50%) within 14 days prior to randomization.
  • Creatinine clearance (CrCl) ≥ 15 mL/minute within 7 days prior to randomization, either measured or calculated using a standard formula (eg, Cockcroft and Gault).
  • Ethical/Other:
  • Written informed consent in accordance with federal, local, and institutional guidelines.
  • Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception.
  • Male subjects must agree to practice contraception.

Who cannot join

  • Disease-related:
  • Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid; ≤ to the equivalent of dexamethasone 40 mg/day for 4 days)
  • Patient with relapsed or refractory multiple myeloma.
  • Patients with non-secretory MM unless serum free light chains are present and the ratio is abnormal.
  • Concurrent Conditions:
  • Pregnant or lactating females (Appendix I).
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  • Major surgery within 21 days prior to randomization.
  • Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to randomization.
  • Known human immunodeficiency virus infection.
  • Active hepatitis B or C infection.
  • Unstable angina or myocardial infarction within 4 months prior to randomization, 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, uncontrolled congestive heart failure (CHF) or uncontrolled diabetes within 14 days prior to randomization.
  • Non-hematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) 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 tumors of the adrenal or pancreas.
  • Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to randomization.
  • 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 to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment.
  • Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomization.
  • 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

1 site in 1 country.

Italy1 site

  • Fondazione EMN Italy Onlus

    Torino, 10126

Other trials in Italy

About this study

Official title: A MULTICENTER, OPEN LABEL STUDY OF WEEKLY CARFILZOMIB, CYCLOPHOSPHAMIDE AND DEXAMETHASONE (wCCyd) IN NEWLY DIAGNOSED MULTIPLE MYELOMA (MM) PATIENTS

This protocol is a phase I/II multicenter study designed to assess the safety and the efficacy of the proposed combinations as up-front treatment in elderly Multiple Myeloma (MM) patients.

Read the detailed description

TREATMENT PERIOD Patients will start the induction treatment with wCCyd, as soon as the screening visits of the pre-treatment period have been terminated.

Each cycle will be repeated every 28 days for a total of 9 courses.

Treatment schedule for 9 cycles of induction:

Phase I:

In the phase I part of the study, the following dose levels of carfilzomib will be studied with constant doses of dexamethasone and cyclophosphamide to define the maximum tolerated dose (MTD):

Level -1

  1. Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15.
  2. Dexamethasone given orally at the dose of 40 mg on days 1, 8, 15, 22 or 20 mg on days 1-2, 8-9,15-16, 22-23.
  3. Carfilzomib given 20 mg/m2 IV once daily on Day 1 of Cycle 1 only followed by 36 mg/m2 on days 8, 15 of Cycle 1, then for all subsequent doses 36 mg/m2 IV once daily on days 1, 8, 15, followed by 14-day rest period (day 16 through 28).

Level 0 (starting dose)

  1. Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15.
  2. Dexamethasone given orally at the dose of 40 mg on days 1, 8, 15, 22 or 20 mg on days 1-2, 8-9,15-16, 22-23.
  3. Carfilzomib given 20 mg/m2 IV once daily on Day 1 of Cycle 1 only followed by 45 mg/m2 on days 8, 15 of Cycle 1, then for all subsequent doses 45 mg/m2 IV once daily on days 1, 8, 15, followed by 14-day rest period (day 16 through 28).

Level +1

  1. Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15.
  2. Dexamethasone given orally at the dose of 40 mg on days 1, 8, 15, 22 or 20 mg on days 1-2, 8-9,15-16, 22-23.
  3. Carfilzomib given 20 mg/m2 IV once daily on Day 1 of Cycle 1 only followed by 56 mg/m2 on days 8, 15 of Cycle 1, then for all subsequent doses 56 mg/m2 IV once daily on days 1, 8, 15, followed by 14-day rest period (day 16 through 28).

Level +2

  1. Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15.
  2. Dexamethasone given orally at the dose of 40 mg on days 1, 8, 15, 22 or 20 mg on days 1-2, 8-9,15-16, 22-23.
  3. Carfilzomib given 20 mg/m2 IV once daily on Day 1 of Cycle 1 only followed by 70 mg/m2 on days 8, 15 of Cycle 1, then for all subsequent doses 70 mg/m2 IV once daily on days 1, 8, 15, followed by 14-day rest period (day 16 through 28).

Patients will be observed during the first cycle of therapy for the assessment of side effects and observation of DLTs. Dose escalation will proceed as follows:

  • 3 patients will be entered at dose level 0.
  • If 0/3 patients experience DLT, dose escalation will continue.
  • If 1/3 patients experience DLT, 3 additional patients will be added to this cohort (max 6).
  • If no further patients experience DLT (1/6) dose escalation will continue.
  • If 2/6 patients experience DLT, the MTD will have been exceeded and the MTD will be the previous dose at which < 2/6 experienced DLT.
  • If 2/3 patients experience a DLT at any given dose, the MTD will have been exceeded and the MTD will be the preceding dose at which < 2/6 (or 1/3) patients experienced a DLT.

Phase II:

The dose used to treat patients in the phase II will be the MTD defined in the phase I of the study.

MAINTENANCE PERIOD At the end of the induction phase, patients will start the maintenance phase with Carfilzomib at the MTD defined by the phase I study IV once daily on days 1, 8, 15 until progression or intolerance.

Treatment schedule for maintenance until progression or intolerance:

Carfilzomib at the MTD defined by phase I study IV once daily on days 1, 8, 15.

Keywords
Multiple myeloma, Diagnosis, Weekly, CCyd
Medical subject headings
Multiple Myeloma, Disease

What participants receive

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

Study groups in NCT01857115
Study groupRoleWhat they receive
CCydExperimentalTreatment schedule for 9 cycles of induction: 1. Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15. 2. Dexamethasone given orally at the dose of 40 mg on days 1, 8, 15, 22 or 20 mg on days 1-2, 8-9,15-16, 22-23. 3. Carfilzomib given 20 mg/m2 IV once daily on Day 1 of Cycle 1 only followed by 36/45/56/70 mg/m2 on days 8, 15 of Cycle 1, then for all subsequent doses 70 mg/m2 IV once daily on days 1, 8, 15, followed by 14-day rest period (day 16 through 28). Treatment schedule for maintenance until progression or intolerance: Carfilzomib at the MTD defined by phase I study IV once daily on days 1, 8, 15.
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. Identification of Dose-limiting toxicity (DLT)

    Non-hematologic:

    • Grade2 neuropathy with pain
    • any Grade 3 toxicity (excluding nausea, vomiting, diarrhea)
    • Grade3 nausea, vomiting, or diarrhea despite maximal antiemetic/antidiarrheal therapy
    • Grade4 fatigue lasting for ≥7days
    • Any non-hematologic toxicity requiring a dose reduction within Cycle1
    • Inability to receive Day 1 dose of Cycle2 due to drug related toxicity persisting from Cycle1 or drug related toxicity newly encountered on Day1 of Cycle2.

    Hematologic:

    • Grade 4 neutropenia (ANC<0.5x109/L) lasting for ≥7days
    • Febrile neutropenia (ANC<1.0x109/L with a fever ≥38.3ºC)
    • Grade 4 thrombocytopenia (platelets<25.0x109/L) lasting ≥7 days despite dose delay
    • Grade 3-4 thrombocytopenia associated with bleeding
    • Any hematologic toxicity requiring a dose reduction within Cycle1
    • Inability to receive Day1 dose of Cycle2 due to drug related toxicity persisting from Cycle1 or drug related toxicity newly encountered on Day1 of Cycle2.

    Measured: 1 year

  2. Partial Response (PR)

    The primary efficacy endpoints will be assessed by considering partial response (PR) following the proposed regimen, at the end of third cycle.

    Measured: 1 year

Secondary outcomes (9)

  1. Response rate (RR)

    Determine the response rate

    Measured: 3 years

  2. Progression free-survival (PFS)

    Determine progression free-survival

    Measured: 3 years

  3. Time to progression (TTP)

    Determine the time to progression

    Measured: 3 years

  4. Duration of response (DOR)

    Determine the duration of response

    Measured: 3 years

  5. Overall survival (OS)

    Determine the overall survival

    Measured: 3 years

  6. Time to next therapy (TTNT)

    Determine the time to next therapy

    Measured: 3 years

  7. Responses

    Determine whether responses obtained with wCCyd treatment are associated with a prolongation of PFS, in comparison with non-responding patients

    Measured: 3 years

  8. Response and survival

    Determine whether tumor response and survival might significantly change in particular subgroups of patients defined on prognostic factors (β2-microglobulin, C-reactive protein (CRP), FISH, gene expression profile)

    Measured: 3 years

  9. Maintenance

    • Determine the benefit on PFS and OS of maintenance with Carfilzomib
    • Determine the benefit on tumor load of maintenance with Carfilzomib

    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 posted20 May 2013 (estimated)
  2. Study startApr 2013
  3. Primary completionNov 2013
  4. Study completion1 Sep 2024

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
63 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01857115
Sponsor's protocol ID
IST-CAR-561
Acronym
wCCyd
Status last verified
Nov 2024
First submitted
17 Apr 2013
Last updated
13 Nov 2024
Results posted
No

Publications

  • Mina R, Bonello F, Petrucci MT, Liberati AM, Conticello C, Ballanti S, Musto P, Olivieri A, Benevolo G, Capra A, Gilestro M, Galieni P, Cavo M, Siniscalchi A, Palumbo A, Montefusco V, Gaidano G, Omede P, Boccadoro M, Bringhen S. Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies. Haematologica. 2021 Apr 1;106(4):1079-1085. doi: 10.3324/haematol.2019.243428.

    PubMed 32107329

  • Montefusco V, Gay F, Spada S, De Paoli L, Di Raimondo F, Ribolla R, Musolino C, Patriarca F, Musto P, Galieni P, Ballanti S, Nozzoli C, Cascavilla N, Ben-Yehuda D, Nagler A, Hajek R, Offidani M, Liberati AM, Sonneveld P, Cavo M, Corradini P, Boccadoro M. Outcome of paraosseous extra-medullary disease in newly diagnosed multiple myeloma patients treated with new drugs. Haematologica. 2020 Jan;105(1):193-200. doi: 10.3324/haematol.2019.219139. Epub 2019 Jun 20.

    PubMed 31221778

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Carfilzomib, Cyclophosphamide and Dexamethasone in people with Multiple Myeloma, run by European Myeloma Network B.V. at 1 site in Italy.

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 20 inclusion and 18 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 13 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Identification of Dose-limiting toxicity (DLT) (time frame: 1 year). The study lists 2 primary outcomes in all. 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 NCT01857115, 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 13 Nov 2024.

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