Carfilzomib, Cyclophosphamide and Dexamethasone In Newly Diagnosed Multiple Myeloma Patients (CCD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2011 by Stichting Hemato-Oncologie voor Volwassenen Nederland
Sponsor:
Collaborator:
Fondazione Neoplasie Sangue Onlus
Information provided by (Responsible Party):
Stichting Hemato-Oncologie voor Volwassenen Nederland
ClinicalTrials.gov Identifier:
NCT01346787
First received: April 19, 2011
Last updated: September 27, 2011
Last verified: September 2011
  Purpose

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).


Condition Intervention Phase
Multiple Myeloma
Drug: CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A MULTICENTER, OPEN LABEL PHASE II STUDY OF CARFILZOMIB, CYCLOPHOSPHAMIDE AND DEXAMETHASONE IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS

Resource links provided by NLM:


Further study details as provided by Stichting Hemato-Oncologie voor Volwassenen Nederland:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response rate [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Duration of Progression Free Survival [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Time to progression (TTP) [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Duration of Response (DOR) [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Duration of Overall Survival [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Time to next therapy [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Progressio Free Survival [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Relation between responses and Progression Free Survival, in responding and non-responding patients.

  • β2-microglobulin as prognostic factors [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Subgroups analysis on prognostic factors

  • peripheral neuropathy [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Rates of peripheral neuropathy, according to the National Cancer Institute Common Toxicity Criteria (version 4.0)

  • Progression Free Survival [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Effect on Progression Free Survival of maintenance with low dose of Carfilzomib (days 1 and 2 every other week)

  • C reactive protein as prognostic factors [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Subgroups analysis on prognostic factors

  • cytogenetics as prognostic factors [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Subgroups analysis on prognostic factors

  • microRNA [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Subgroups analysis on prognostic factors

  • gene expression profile [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Subgroups analysis on prognostic factors

  • Overall Survival [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Effect on Overall Survival of maintenance with low dose of Carfilzomib (days 1 and 2 every other week)


Estimated Enrollment: 53
Study Start Date: July 2011
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carfilzomib Cyclophosphamide Dexamethasone
The 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.
Drug: CARFILZOMIB, CYCLOPHOSPHAMIDE, DEXAMETHASONE
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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

Exclusion Criteria:

  • - 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)
  • 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)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01346787

Locations
Italy
azienda ospedaliero-universitaria umberto I Clinica di Ematologia Recruiting
Ancona, Italy, 60020
Contact: Massimo Offidani, MD    0039 0715964735    m.offidani@ospedaliriuniti.marche.it   
Principal Investigator: Massimo Offidani, MD         
Policlinico S. Orsola Istituto di Ematologia e Oncologia Medica Not yet recruiting
Bologna, Italy, 40138
Contact: Michele Cavo, MD    0039 051 6363680    michele.cavo@unibo.it   
Principal Investigator: Michele Cavo, MD         
Ospedale Ferrarotto_Reparto di Ematologia Recruiting
Catania, Italy, 95124
Contact: Francesco Di Raimondo, MD    0957435969    diraimon@unict.it   
Principal Investigator: Francesco Di Raimondo, MD         
Az.Osp. Di Careggi_Dh ematologia Active, not recruiting
Firenze, Italy, 50134
Istituto Nazionale per lo Studio e la Cura dei Tumori_UO Ematologia_Trapianto di Midollo Osseo Allogenico Active, not recruiting
Milano, Italy, 20133
Divisione di Ematologia Dipartimento di Medicina Clinica e Sperimentale Università Amedeo Avogadro Active, not recruiting
Novara, Italy, 28100
IRCCS CROB UOC di Ematologia e trapianto cellule staminali Ospedale Oncologico Regionale Recruiting
Rionero in Vulture PZ, Italy
Contact: Pellegrino Musto, MD    0972726217    pellegrino.musto@crob.it   
Principal Investigator: Pellegrino Musto, MD         
Divisione di ematologia ospedale s.eugenio Active, not recruiting
Roma, Italy
Cattedra di ematologia Università La Sapienza Active, not recruiting
Roma, Italy
S.C.di Oncoematologia, Azienda Ospedaliera S. Maria di Terni Active, not recruiting
Terni, Italy
Division of Hematology, A.O.U. San Giovanni Battista Recruiting
Torino, Italy, 10126
Contact: Sara Bringhen, MD       gismm2001@yahoo.com   
Contact: Antonio Palumbo, MD       gismm2001@yahoo.com   
Principal Investigator: Sara Bringhen, MD         
Sub-Investigator: Antonio Palumbo, MD         
Sub-Investigator: Mario Boccadoro, MD         
Az. Osp. San Giovanni Battista - Molinette_Ematologia 2 Recruiting
Torino, Italy, 10126
Contact: Umberto Vitolo, MD    011/6335550    uvitolo@molinette.piemonte.it   
Principal Investigator: Umberto Vitolo, MD         
Netherlands
Erasmus MC Active, not recruiting
Rotterdam, Netherlands
Sponsors and Collaborators
Stichting Hemato-Oncologie voor Volwassenen Nederland
Fondazione Neoplasie Sangue Onlus
  More Information

No publications provided by Stichting Hemato-Oncologie voor Volwassenen Nederland

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Stichting Hemato-Oncologie voor Volwassenen Nederland
ClinicalTrials.gov Identifier: NCT01346787     History of Changes
Other Study ID Numbers: IST-CAR-506
Study First Received: April 19, 2011
Last Updated: September 27, 2011
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Stichting Hemato-Oncologie voor Volwassenen Nederland:
carfilzomib
dexamethasone
cyclophosphamide
multiple myeloma
newly diagnosed

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Cyclophosphamide
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Alkylating Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents

ClinicalTrials.gov processed this record on October 21, 2014