Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Subcutaneous Velcade Plus Oral Melphalan and Prednisone or Plus Cycloposphamide and Prednisone or Plus Prednisone

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01190787
Recruitment Status : Active, not recruiting
First Posted : August 30, 2010
Last Update Posted : August 2, 2018
Sponsor:
Collaborator:
Fondazione Neoplasie Sangue Onlus
Information provided by (Responsible Party):
Stichting Hemato-Oncologie voor Volwassenen Nederland

Tracking Information
First Submitted Date  ICMJE August 27, 2010
First Posted Date  ICMJE August 30, 2010
Last Update Posted Date August 2, 2018
Actual Study Start Date  ICMJE July 2010
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2011)
Very Good Partial Response, Complete response rate , Partial response rate [ Time Frame: 5 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 27, 2010)
  • Very Good Partial Response [ Time Frame: 5 years ]
  • Complete response rate [ Time Frame: 5 years ]
  • Partial response rate [ Time Frame: 5 years ]
Change History Complete list of historical versions of study NCT01190787 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2010)
  • Progression free survival [ Time Frame: 5 years ]
  • Time to progression [ Time Frame: 5 years ]
  • Time to Next Therapy [ Time Frame: 5 years ]
  • Overall survival [ Time Frame: 5 years ]
  • Time to response [ Time Frame: 5 years ]
  • Duration of response [ Time Frame: 5 years ]
  • Response rate [ Time Frame: 5 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Subcutaneous Velcade Plus Oral Melphalan and Prednisone or Plus Cycloposphamide and Prednisone or Plus Prednisone
Official Title  ICMJE A Multicenter Phase II Study of Subcutaneous Velcade Plus Oral Melphalan and Prdnisone or Plus Cycloposphamide and Prednisone or Plus Prednisone in Newly Diagnosed Elderly Multiple Myeloma Patients
Brief Summary This protocol is a single-arm, three-cohort, phase II multicenter study designed to assess the safety and the efficacy of three all-oral combinations: Velcade with continuous low-dose melphalan and prednisone (VMP) or with continuous low-dose cyclophosphamide and prednisone (VCP) or Velcade with low-dose prednisone could be effective and well tolerated (VP).
Detailed Description

This protocol is a single-arm, three-cohort, phase II multicenter study designed to assess the safety and the efficacy of VMP and VCP and VP as up-front treatment in elderly MM patients. The combination of weekly subcutaneous administrations of Velcade with continuous low-dose melphalan and prednisone (VMP) or with continuous low-dose cyclophosphamide and prednisone (VCP) or Velcade with low-dose prednisone could be effective and well tolerated (VP).

Patients will be evaluated at scheduled visits in up to 3 study periods: pre-treatment, treatment and long-term follow-up (LTFU).

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 induction and maintenance.

Subjects receive:

  1. Induction therapy:

    nine 4-week courses of Velcade/Melphalan/Prednisone (VMP) or nine 4-week courses of Velcade/Cyclophosphamide/Prednisone (VCP) or Nine 4-week courses of Velcade/Prednisone (VP).

  2. Maintenance therapy:

Velcade alone During the induction period patients will attend periodic study centre visits each scheduled Velcade administration in order to asses the toxicity and efficacy of the treatment. During the maintenance period, all patients will attend study centre visits every 4 weeks, until development of confirmed PD. The response will be assessed after each cycle.

During the LTFU period, after development of confirmed PD, all patients are to be followed for survival during the LTFU period every 3 months via telephone or office visit.

The duration of treatment period, including the maintenance treatment is approximately 3 years. The duration of LTFU is approximately 2 years, for a total of 5 years. the occurance of PD will determine the duration of progression-free survival of each patient(secondary objective). The occurrence of death will determine the duration of overall survival (secondary objective).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: velcade subcutaneous melphalan prednisone

    INDUCTION Velcade will be given as subcutaneous (SC) injection. Each cycle will be repeated every 28 days.

    Melphalan will be given orally. Each cycle will be repeated every 28 days. Prednisone will be given orally.Each cycle will be repeated every 28 days. MAINTENANCE Velcade will be given a SC injection. Each cycle will be repeated every 28 days.

    Other Name: Bortezomib, Alkeran, Deltacortene
  • Drug: velcade cyclophosphamide prednisone

    INDUCTION Velcade will be given as subcutaneous (SC) injection. Each cycle will be repeated every 28 days.

    Cyclophosphamide will be given orally. Each cycle will be repeated every 28 days.

    Prednisone will be given orally.Each cycle will be repeated every 28 days. MAINTENANCE Velcade will be given a SC injection. Each cycle will be repeated every 28 days.

    Other Name: Bortezomib,Endoxan, deltacortene
  • Drug: velcade prednisone

    INDUCTION Velcade will be given as subcutaneous (SC) injection. Each cycle will be repeated every 28 days.

    Prednisone will be given orally.Each cycle will be repeated every 28 days. MAINTENANCE Velcade will be given a SC injection. Each cycle will be repeated every 28 days.

    Other Name: Bortezomib, deltacortene
Study Arms  ICMJE
  • Experimental: VMP

    INDUCTION Velcade will be given as subcutaneous (SC) injection. Each cycle will be repeated every 28 days.

    Melphalan will be given orally. Each cycle will be repeated every 28 days. Prednisone will be given orally.Each cycle will be repeated every 28 days. MAINTENANCE Velcade will be given a SC injection. Each cycle will be repeated every 28 days.

    Intervention: Drug: velcade subcutaneous melphalan prednisone
  • Experimental: VCP

    INDUCTION Velcade will be given as subcutaneous (SC) injection. Each cycle will be repeated every 28 days.

    Cyclophosphamide will be given orally. Each cycle will be repeated every 28 days.

    Prednisone will be given orally.Each cycle will be repeated every 28 days. MAINTENANCE Velcade will be given a SC injection. Each cycle will be repeated every 28 days.

    Intervention: Drug: velcade cyclophosphamide prednisone
  • Experimental: VP

    INDUCTION Velcade will be given as subcutaneous (SC) injection. Each cycle will be repeated every 28 days.

    Prednisone will be given orally.Each cycle will be repeated every 28 days. MAINTENANCE Velcade will be given a SC injection. Each cycle will be repeated every 28 days.

    Intervention: Drug: velcade prednisone
Publications * 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. Erratum in: Blood. 2016 Mar 3;127(9):1213. Erratum in: Blood. 2016 Mar 3;127(9):1213. Blood. 2016 Aug 18;128(7):1020.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 27, 2010)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2020
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 75 years old or age < 75 years with abnormal cardiac, pulmonary, renal or hepatic function (unsuitable for protocol with standard inclusion/exclusion criteria).
  • 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.
  • Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) during study drug therapy (including dose interruption) and for 4 weeks after discontinuation of Velcade therapy.
  • Female patient is either post-menopausal for 24 consecutive months or surgically sterilised or agree to continuous abstinence from heterosexual sexual contact or willing to use two acceptable method of birth control at the same time (one highly effective method and one additional effective method) (Highly Effective Methods: Intrauterine device -IUD-; Hormonal -birth control pills, injections, implants-; tubal ligation; partner's vasectomy; Additional Effective Methods: Latex condom; Diaphragm; Cervical Cap) for 4 weeks prior to beginning study drug therapy, during study drug therapy (including dose interruption) and for 4 weeks after discontinuation of therapy.
  • Patient was a newly diagnosed multiple myeloma based on standard criteria
  • Patient has measurable disease, defined as follows:
  • Secretory myeloma: any quantifiable serum monoclonal protein value (generally, but not necessarily, greater than 1 g/dL of IgG M-Protein and greater than 0.5 g/dL of IgA M-Protein) and, where applicable, urine light-chain excretion of >200 mg/24 hours;
  • Non-secretory myeloma: > 30% plasma cells in the bone marrow and at least one plasmacytoma > 2 cm as determined by clinical examination or applicable radiographs (i.e., MRI or CT scan).
  • Patient has a Karnofsky performance status > 50%.
  • Patient has a life-expectancy >3 months
  • Pretreatment clinical laboratory values within 14 days of enrolment:
  • platelet count ≥ 80x109/L
  • hemoglobin ≥ 8 g/dL
  • absolute neutrophil count (ANC) ≥ 1.0x109/L
  • AST ≤ 2.5 times the upper limit of normal
  • ALT ≤ 2.5 times the upper limit of normal
  • total bilirubin ≤ 1.5 times the upper limit of normal
  • cleareance creatinine ≥ 20 ml/min

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality or psychiatric illness that prevented the subject from signing the informed consent form or placed the subjects at unacceptable risk.
  • 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).
  • Pregnant or lactating females
  • Known positive for HIV or active infectious hepatitis type A, B or C
  • Peripheral neuropathy or neuropatic pain grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 3.0
  • Infiltrative pulmonary disease
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01190787
Other Study ID Numbers  ICMJE 26866138MMY2069
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Stichting Hemato-Oncologie voor Volwassenen Nederland
Study Sponsor  ICMJE Stichting Hemato-Oncologie voor Volwassenen Nederland
Collaborators  ICMJE Fondazione Neoplasie Sangue Onlus
Investigators  ICMJE
Principal Investigator: Antonio Palumbo, MD Division of Hematology, A.O.U. San Giovanni Battista
PRS Account Stichting Hemato-Oncologie voor Volwassenen Nederland
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP