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Multiple MyelomaPhase 2CCDNCT01346787

Carfilzomib, Cyclophosphamide and Dexamethasone In Newly Diagnosed Multiple Myeloma Patients

A Phase 2 study testing CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE in people with Multiple Myeloma, run by European Myeloma Network B.V. at 13 sites in 2 countries.

Completed

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

Official record
Search all trials

Trial summary

The purpose of this study is to determine whether the association of Carfilzomib, Cyclophosphamide and Dexamethasone (CCd) as induction treatment is safe and provides benefits in patients with newly diagnosed Multiple Myeloma (MM). 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, DEXAMETHASONE
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
13 sitesin 2 countries
Study dates
Jul 2011to 31 May 2023
Phase
Phase 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
  • Female patient is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
  • Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) for the duration of the study.
Show all 18Show fewer
  • 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

Who cannot join

  • - Patients with non-secretory MM, unless serum free light chains are present and the ratio is abnormal.
  • Pregnant or lactating females
  • Patient has active infectious hepatitis type B or C or HIV.
  • 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)
  • Peripheral neuropathy > CTCAE grade 2 and ≥ grade 2 painful peripheral neuropathy (with the difference being in the exclusion of patients with Grade 2 painful PN).
  • Known history of allergy to Capsidol (a cyclodextrin derivative used to solubilize carfilzomib)
Show all 10Show fewer
  • 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

13 sites in 2 countries.

13 sites in 2 countries

Italy12 sites

  • azienda ospedaliero-universitaria umberto I Clinica di Ematologia

    Ancona, 60020

  • Policlinico S. Orsola Istituto di Ematologia e Oncologia Medica

    Bologna, 40138

  • Ospedale Ferrarotto_Reparto di Ematologia

    Catania, 95124

  • Az.Osp. Di Careggi_Dh ematologia

    Florence, 50134

  • Istituto Nazionale per lo Studio e la Cura dei Tumori_UO Ematologia_Trapianto di Midollo Osseo Allogenico

    Milan, 20133

  • Divisione di Ematologia Dipartimento di Medicina Clinica e Sperimentale Università Amedeo Avogadro

    Novara, 28100

  • IRCCS CROB UOC di Ematologia e trapianto cellule staminali Ospedale Oncologico Regionale

    Rionero in Vulture, PZ, 85100

  • Cattedra di ematologia Università La Sapienza

    Roma

  • Divisione di Ematologia Ospedale S. Eugenio

    Roma

  • S.C.di Oncoematologia, Azienda Ospedaliera S. Maria di Terni

    Terni

  • SC Ematologia - A.O.U. Città della Salute e della Scienza di Torino

    Torino, 10126

  • SSD CLINICAL TRIAL IN ONCOEMATOLOGIA E MIELOMA MULTIPLO - A.O.U. Città della Salute e della Scienza di Torino

    Torino, 10126

Other trials in Italy

Netherlands1 site

  • Erasmus MC

    Rotterdam

Other trials in Netherlands

About this study

Official title: A MULTICENTER, OPEN LABEL PHASE II STUDY OF CARFILZOMIB, CYCLOPHOSPHAMIDE AND DEXAMETHASONE IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS

The purpose of this study is to determine whether the association of Carfilzomib, Cyclophosphamide and Dexamethasone (CCd) as induction treatment is safe and provides benefits in patients with newly diagnosed Multiple Myeloma (MM).

Read the detailed description

This protocol is a phase II multicenter, international, non-comparative, open label study designed to jointly assess the safety and the efficacy of the association Carfilzomib with Cyclophosphamide and Dexamethasone (CCd) as induction treatment and Carfilzomib alone as maintenance in newly diagnosed MM patients.

Patients will be evaluated at scheduled visits in up to 4 study periods: pre-treatment, treatment, maintenance and long-term follow-up.

The pre-treatment period includes screening visits, performed at study entry. After providing written informed consent to participate in the study, patients will be evaluated for study eligibility. The screening period includes the availability of inclusion criteria described above.

The treatment period includes administration of Carfilzomib, Cyclophosphamide and Dexamethasone for 9 4-week courses. In order to assess the toxicity of treatment, patients will attend the study centre visits at each scheduled Carfilzomib administration. The response will be assessed after each 4-week cycle.

The maintenance period includes carfilzomib alone on days 1, 2, 15, 16 at 36mg/m2. For patients who show evidence of progression during maintenance phase, the frequency of Carfilzomib can be increased to days 1, 2, 8, 9, 15, 16 at the discretion of the investigator. It will be initiated at the end of the 9th course and will be stopped at progression or intolerance. The median expected duration of the maintenance treatment is approximately 2 years.

The Long Term Follow Up periods will start after development of confirmed Progression Disease, all patients are to be followed for survival during the Long Term Follow Up period every 3 months via telephone or office visit.

Approximately 15 Italian centers and foreign centers will participate to the protocol.

Patients with symptomatic newly diagnosed MM whose age is ≥ 65 years or who are ineligible for autologous stem cell transplantation. Up to 53 patients will be enrolled from different centers.

The duration of the treatment is approximately 9 months. This length of time is required to complete 9 courses of CCd. At the end of the first stage (19 patients), the trial will be temporarily stopped until all 19 patients complete the toxicity and efficacy evaluation (3 cycle): if there are more than 7 responses and less than 8 toxicities, a further group of 34 patients (total=53) will be enrolled. Otherwise, the trial will be definitively stopped or the DSMC will recommend testing other doses of the drugs.

The maintenance period in both phases will start at the end of the 9th course and will be stopped at progression or intolerance. The median expected duration of the maintenance treatment is approximately 2 years. The duration of follow-up from relapse will be approximately 2 years. The occurrence of PD will determine the duration of TTP of each patient. The occurrence of death will determine the duration of overall survival. The first analysis to evaluate safety and efficacy is planned when the 19 patients enrolled in the first stage of the study have completed the third cycle of induction treatment.

The trial will be stopped if there are < 6 responses, or > 9 toxicities or the Data Safety Monitoring Committee recommends testing other doses of the drugs; Otherwise, a further group of 34 patients (total=53) will be enrolled. The final conclusion will be negative if there are ≤ 23/53 responses, or ≥ 20/53 drug-related toxicities.

Being tested
CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE
Keywords
carfilzomib, dexamethasone, cyclophosphamide, multiple myeloma, newly diagnosed
Medical subject headings
Multiple Myeloma

What participants receive

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

  • CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONEDrug

    Patients will start induction treatment with Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15. Low dose Dexamethasone will be 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 = 20 mg/m2 IV once daily on days 1, 2, of cycle 1 only followed by 36 mg/ m2 days 8, 9, 15, 16 in cycle 1, then for all subsequent doses 36 mg/ m2 IV once daily on days 1, 2, 8, 9, 15, 16, followed by 13-day rest period (day 17 through 28). Each cycle will be repeated every 28 days for a total of 9 courses. MANTEINANCE PERIOD At the end of induction phase (9 courses), maintenance phase with Carfilzomib alone IV at 36 mg/ m2 IV on days 1, 2, 15, 16 will start, until progression or intolerance. For patients who show evidence of progression during maintenance phase, the frequency of Carfilzomib can be increased to days 1, 2, 8, 9, 15, 16 at the discretion of the investigator, or the patient may be removed from the study

Study groups in NCT01346787
Study groupRoleWhat they receive
Carfilzomib Cyclophosphamide DexamethasoneExperimentalThe treatment period includes administration of Carfilzomib Cyclophosphamide Dexamethasone for 9 courses. In order to assess the toxicity of treatment, patients will attend the study centre visits at each scheduled carfilzomib administration. The response will be assessed after each cycle.
Receives: Drug: CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE

What is being measured

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

  1. Toxicity: 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)

    Toxicity is defined as the first occurrence of a grade 4 hematologic drug-related toxicity excluding anemia, (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) with the exception of (grade 4 neutropenia > 3 days , or grade 4 thrombocytopenia >7 days duration) or grade 3 non-hematologic drug-related toxicity.

    Measured: 4 years

  2. Efficacy will be assessed by considering partial response (PR) following the proposed regimen. Assessment of Partial Response rate will be performed at the end of third cycle according to the criteria of the International Myeloma Working Group.

    Measured: 4 years

Secondary outcomes (15)

  1. Response rate

    Measured: 4 years

  2. Duration of Progression Free Survival

    Measured: 4 years

  3. Time to progression (TTP)

    Measured: 4 years

  4. Duration of Response (DOR)

    Measured: 4 years

  5. Duration of Overall Survival

    Measured: 4 years

  6. Time to next therapy

    Measured: 4 years

  7. Progressio Free Survival

    Relation between responses and Progression Free Survival, in responding and non-responding patients.

    Measured: 4 years

  8. β2-microglobulin as prognostic factors

    Subgroups analysis on prognostic factors

    Measured: 4 years

  9. peripheral neuropathy

    Rates of peripheral neuropathy, according to the National Cancer Institute Common Toxicity Criteria (version 4.0)

    Measured: 4 years

  10. Progression Free Survival

    Effect on Progression Free Survival of maintenance with low dose of Carfilzomib (days 1 and 2 every other week)

    Measured: 4 years

  11. C reactive protein as prognostic factors

    Subgroups analysis on prognostic factors

    Measured: 4 years

  12. cytogenetics as prognostic factors

    Subgroups analysis on prognostic factors

    Measured: 4 years

  13. microRNA

    Subgroups analysis on prognostic factors

    Measured: 4 years

  14. gene expression profile

    Subgroups analysis on prognostic factors

    Measured: 4 years

  15. Overall Survival

    Effect on Overall Survival of maintenance with low dose of Carfilzomib (days 1 and 2 every other week)

    Measured: 4 years

Timeline

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

  1. First posted3 May 2011 (estimated)
  2. Study startJul 2011
  3. Primary completionOct 2012
  4. Study completion31 May 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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01346787
Sponsor's protocol ID
IST-CAR-506
Acronym
CCD
Status last verified
Sep 2023
First submitted
19 Apr 2011
Last updated
8 Sep 2023
Results posted
No
Data monitoring committee
Yes

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

  • Bringhen S, Mina R, Petrucci MT, Gaidano G, Ballanti S, Musto P, Offidani M, Spada S, Benevolo G, Ponticelli E, Galieni P, Cavo M, Di Toritto TC, Di Raimondo F, Montefusco V, Palumbo A, Boccadoro M, Larocca A. Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: a pooled analysis of two phase I/II studies. Haematologica. 2019 Aug;104(8):1640-1647. doi: 10.3324/haematol.2018.208272. Epub 2019 Feb 7.

    PubMed 30733270

  • Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, Offidani M, McCarthy P, Evangelista A, Lonial S, Zweegman S, Musto P, Terpos E, Belch A, Hajek R, Ludwig H, Stewart AK, Moreau P, Anderson K, Einsele H, Durie BG, Dimopoulos MA, Landgren O, San Miguel JF, Richardson P, Sonneveld P, Rajkumar SV. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015 Mar 26;125(13):2068-74. doi: 10.1182/blood-2014-12-615187. Epub 2015 Jan 27.

    PubMed 25628469

  • Bringhen S, Petrucci MT, Larocca A, Conticello C, Rossi D, Magarotto V, Musto P, Boccadifuoco L, Offidani M, Omede P, Gentilini F, Ciccone G, Benevolo G, Genuardi M, Montefusco V, Oliva S, Caravita T, Tacchetti P, Boccadoro M, Sonneveld P, Palumbo A. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study. Blood. 2014 Jul 3;124(1):63-9. doi: 10.1182/blood-2014-03-563759. Epub 2014 May 22.

    PubMed 24855212

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE in people with Multiple Myeloma, run by European Myeloma Network B.V. at 13 sites in 2 countries.

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 10 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 8 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Italy, Netherlands. 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?

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?

Toxicity: 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) (time frame: 4 years). 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 NCT01346787, which also lists 5 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 8 Sep 2023.

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