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Multiple MyelomaPhase 1/2CCDNCT02204241

Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients

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 years and older
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
36 participants
Where
1 siteItaly
Study dates
Jun 2014to Apr 2023
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 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • Patient is of a legally consenting age as defined by local regulations.
  • Patient is age ≥ 65 year of age or who are ineligible for autologous stem cell transplantation.
  • Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
  • Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
  • Women of childbearing potential must have a negative serum pregnancy test within the 7 days prior to study drug administration and a negative urine pregnancy test within the 3 days prior to the first study drug administration.
  • Women of childbearing potential and male subjects who are sexullay active with WOCBP must agree to use 2 highly effective methods of contraception during the study and for 30 days following the last dose of study treatment including a male condom.
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  • Patient is a newly diagnosed MM patient.
  • 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.
  • Patient has a Karnofsky performance status ≥60%.
  • Patient has a life-expectancy >3 months.
  • Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1, before study drug administration):
  • Platelet count ≥50 x 109/L (≥30 x 109 /L if myeloma involvement in the bone marrow is > 50%) within 14 days prior to drug administration.
  • Absolute neutrophil count (ANC) ≥ 1 x 109/L without the use of growth factors.
  • Corrected serum calcium ≤14 mg/dL (3.5 mmol/L)
  • Alanine transaminase (ALT): ≤ 3 x the ULN.
  • Total bilirubin: ≤ 2 x the ULN.
  • Calculated or measured creatinine clearance: ≥ 15 mL/minute
  • LVEF ≥40%. 2D transthoracic ECHO is the preferred method of evaluation. Multigated Acquisition Scan is acceptable if ECHO is not available

Who cannot join

  • Patients with non-secretory MM, unless serum free light chains are present and the ratio is abnormal.
  • Women who are pregnant and/or breast feeding.
  • Patient has active infectious hepatitis type B or C or HIV.
  • Pulmonary Hypertension.
  • QTc Interval ≥ 450 msec.
  • Uncontrolled Atrial Fibrillation/Flutter.
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  • History of Torsade de pointe, Ventricular Tachycardia, Ventricular Fibrillation.
  • Uncontrolled Infection.
  • Patients with myocardial infarction or unstable angina ≤ 4 months or other clinically significant heart disease (e.g., CHF NY Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
  • Patient with peripheral neuropathy > CTCAE grade 2.
  • 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 baseline.
  • Patient has any other clinically significant illness that would, in the investigator's opinion, increase the patient's risk for toxicity.
  • Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix or breast, or localized prostate cancer of Gleason score <7 with a stable PSA).

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 Phase I/II Study of Carfilzomib, Cyclophosphamide and Dexamethasone 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 schedule for 9 cycles of induction:

Phase I:

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

Level-1:

  1. Carfilzomib given 20 mg/m2 IV once daily on days 1-2 of Cycle 1 only followed by 36 mg/m2 on days 8-9, 15-16, of Cycle 1, then for all subsequent doses 36 mg/m2 IV once daily on days 1-2, 8-9, 15-16.
  2. Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15
  3. 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

Level 0:

  1. Carfilzomib given 20 mg/m2 IV once daily on days 1-2 of Cycle 1 only followed by 45 mg/m2 on days 8-9, 15-16, of Cycle 1, then for all subsequent doses 45 mg/m2 IV once daily on days 1-2, 8-9, 15-16.
  2. Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15
  3. 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

Level +1:

  1. Carfilzomib given 20 mg/m2 IV once daily on days 1-2 of Cycle 1 only followed by 56 mg/m2 on days 8-9, 15-16, of Cycle 1, then for all subsequent doses 56 mg/m2 IV once daily on days 1-2, 8-9, 15-16.
  2. Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15
  3. 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

Level +2:

  1. Carfilzomib given 20 mg/m2 IV once daily on days 1-2 of Cycle 1 only followed by 36 mg/m2 on days 8-9, 15-16, of Cycle 1, then for all subsequent doses 70 mg/m2 IV once daily on days 1-2, 8-9, 15-16.
  2. Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15
  3. 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

Patient will be observed at the end of the second 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.

Treatment schedule for maintenance until progression or intolerance:

Carfilzomib at the MTD defined by phase I study IV once daily on days 1-2, 15-16.

Keywords
Multiple myeloma, Diagnosis, 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 NCT02204241
Study groupRoleWhat they receive
CCydExperimentalTreatment schedule for 9 cycles of induction: Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15. 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. Carfilzomib given 20 mg/m2 IV once daily on Day 1-2 of Cycle 1 only followed by 36/45/56/70 mg/m2 on days 8-9, 15-16 of Cycle 1, then for all subsequent doses 36/45/56/70 mg/m2 IV once daily on days 1-2, 8-9, 15-16, followed by 12-day rest period (day 17 through 28). Treatment schedule for maintenance until progression or intolerance: Carfilzomib at the MTD defined by phase I study IV once daily on days 1-2, 15-16.
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. Dose Limiting Toxicity (DLT)

    Non-hematologic:

    • Grade 2 neuropathy with pain
    • any Grade 3 tox. (excluding nausea, vomiting, diarrhea)
    • Grade 3 nausea, vomiting, or diarrhea despite maximal antiemetic/antidiarrheal therapy
    • Grade 4 fatigue lasting for ≥ 7 days
    • Any non-hematologic tox. requiring a dose reduction within Cycle 1
    • Inability to receive Day 1 dose of Cycle 2 due to drug related tox. persisting from Cycle 1 or drug related tox. newly encountered on Day 1 of Cycle 2.

    Hematologic:

    • Grade 4 neutropenia (ANC < 0.5 x 109/L) lasting for ≥ 7 days
    • Febrile neutropenia (ANC < 1.0 x 109/L with a fever ≥ 38.3ºC)
    • Grade 4 thrombocytopenia (platelets < 25.0 x 109/L) lasting ≥ 7 days despite dose delay
    • Grade 3-4 thrombocytopenia associated with bleeding
    • Any hematologic tox. requiring a dose reduction within Cycle 1
    • Inability to receive Day 1 dose of Cycle 2 due to drug related tox. persisting from Cycle 1 or drug related tox. newly encountered on Day 1 of Cycle 2.

    Measured: 1 year

Secondary outcomes (10)

  1. Response rate (RR)

    Determine the response rate

    Measured: 3 years

  2. Progression-free survival (PFS)

    Determine the progression-free survival (PFS)

    Measured: 3 years

  3. Time to progression (TTP)

    Determine the time to progression (TTP)

    Measured: 3 years

  4. Duration of response (DOR)

    Determine the duration of response (DOR)

    Measured: 3 years

  5. Overall survival (OS)

    Determine the overall survival (OS)

    Measured: 3 years

  6. Time to next therapy (TTNT)

    Determine the time to next therapy (TTNT)

    Measured: 3 years

  7. Responses

    Determine whether responses obtained with CCyd 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 outcome may change in subgroups with different prognosis according to current 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

    Measured: 3 years

  10. Adverse event

    The toxicity is defined as the first occurrence of a grade 4 hematologic drug-related toxicity (grade 4 neutropenia must last longer than 3 days and grade 4 thrombocytopenia must last longer than 7 days in order to be considered a toxicity) excluding anemia. Assessment of adverse events will be performed at the end of third cycle according to the National Cancer Institute Common Terminology Criteria of Adverse Events (CTCAE version 4.0).

    Measured: 1 years

Timeline

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

  1. First posted30 Jul 2014 (estimated)
  2. Study startJun 2014
  3. Primary completionJun 2015
  4. Study completionApr 2023

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
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02204241
Sponsor's protocol ID
IST-CAR-601
Acronym
CCD
Status last verified
May 2023
First submitted
4 Jul 2014
Last updated
3 Jul 2023
Results posted
No
Data monitoring committee
No

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 18 inclusion and 15 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 3 Jul 2023. 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?

Dose Limiting Toxicity (DLT) (time frame: 1 year). 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 NCT02204241.

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 3 Jul 2023.

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