ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02204241
Recruitment Status : Recruiting
First Posted : July 30, 2014
Last Update Posted : May 10, 2016
Sponsor:
Collaborator:
Fondazione Neoplasie Sangue Onlus
Information provided by (Responsible Party):
Stichting Hemato-Oncologie voor Volwassenen Nederland

Brief 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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Carfilzomib Drug: Cyclophosphamide Drug: Dexamethasone Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 71 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open Label Phase I/II Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma (MM) Patients
Study Start Date : June 2014
Actual Primary Completion Date : June 2015
Estimated Study Completion Date : June 2019


Arm Intervention/treatment
Experimental: CCyd

Treatment 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.

Drug: Carfilzomib
Drug: Cyclophosphamide
Drug: Dexamethasone



Primary Outcome Measures :
  1. Dose Limiting Toxicity (DLT) [ Time Frame: 1 year ]

    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.


Secondary Outcome Measures :
  1. Response rate (RR) [ Time Frame: 3 years ]
    Determine the response rate

  2. Progression-free survival (PFS) [ Time Frame: 3 years ]
    Determine the progression-free survival (PFS)

  3. Time to progression (TTP) [ Time Frame: 3 years ]
    Determine the time to progression (TTP)

  4. Duration of response (DOR) [ Time Frame: 3 years ]
    Determine the duration of response (DOR)

  5. Overall survival (OS) [ Time Frame: 3 years ]
    Determine the overall survival (OS)

  6. Time to next therapy (TTNT) [ Time Frame: 3 years ]
    Determine the time to next therapy (TTNT)

  7. Responses [ Time Frame: 3 years ]
    Determine whether responses obtained with CCyd treatment are associated with a prolongation of PFS, in comparison with non-responding patients

  8. Response and survival [ Time Frame: 3 years ]
    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)

  9. Maintenance [ Time Frame: 3 years ]
    Determine the benefit on PFS and OS of maintenance with carfilzomib

  10. Adverse event [ Time Frame: 1 years ]
    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).



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
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.
  • 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.
  • 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

Exclusion Criteria:

  • 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.
  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02204241


Locations
Italy
FO.NE.SA.Onlus Recruiting
Torino, Italy, 10126
Contact: Lorenzo Perinetto    +390116336728    gismm2001@yahoo.com   
Sponsors and Collaborators
Stichting Hemato-Oncologie voor Volwassenen Nederland
Fondazione Neoplasie Sangue Onlus

Responsible Party: Stichting Hemato-Oncologie voor Volwassenen Nederland
ClinicalTrials.gov Identifier: NCT02204241     History of Changes
Other Study ID Numbers: IST-CAR-601
First Posted: July 30, 2014    Key Record Dates
Last Update Posted: May 10, 2016
Last Verified: May 2016

Keywords provided by Stichting Hemato-Oncologie voor Volwassenen Nederland:
Multiple myeloma
Diagnosis
CCyd

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Cyclophosphamide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors