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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2011 by Stichting Hemato-Oncologie voor Volwassenen Nederland
Sponsor:
Collaborator:
Fondazione Neoplasie Sangue Onlus
Information provided by:
Stichting Hemato-Oncologie voor Volwassenen Nederland
ClinicalTrials.gov Identifier:
NCT01190787
First received: August 27, 2010
Last updated: May 3, 2011
Last verified: May 2011
  Purpose

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).


Condition Intervention Phase
Multiple Myeloma
Drug: velcade subcutaneous melphalan prednisone
Drug: velcade cyclophosphamide prednisone
Drug: velcade prednisone
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 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Very Good Partial Response, Complete response rate , Partial response rate [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Time to progression [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Time to Next Therapy [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Time to response [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Duration of response [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Response rate [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 150
Study Start Date: July 2010
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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
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.

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
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.

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

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01190787

Contacts
Contact: Antonio Palumbo, MD +39011633 ext 4260 appalumbo@yahoo.com
Contact: Mario Boccadoro, MD +39011633 ext 6728 mario.boccadoro@unito.it

Locations
Italy
Division of Hematology, A.O.U. San Giovanni Battista Recruiting
Torino, Italy, 10126
Contact: Antonio Palumbo, MD    +39011633 ext 4260    appalumbo@yahoo.com   
Contact: Mario Boccadoro, MD    +39011633 ext 6728    mario.boccadoro@unito.it   
Sponsors and Collaborators
Stichting Hemato-Oncologie voor Volwassenen Nederland
Fondazione Neoplasie Sangue Onlus
Investigators
Principal Investigator: Antonio Palumbo, MD Division of Hematology, A.O.U. San Giovanni Battista
  More Information

No publications provided

Responsible Party: P. Sonneveld, DM Stinenbosch, Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON)
ClinicalTrials.gov Identifier: NCT01190787     History of Changes
Other Study ID Numbers: 26866138MMY2069
Study First Received: August 27, 2010
Last Updated: May 3, 2011
Health Authority: Italy: Ethics Committee

Keywords provided by Stichting Hemato-Oncologie voor Volwassenen Nederland:
Multiple Myeloma
Elderly Patients
Diagnosis
Velcade subcutaneous
Prednisone
Melphalan
Cyclophosphamide

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
Cyclophosphamide
Melphalan
Bortezomib
Prednisone
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Glucocorticoids

ClinicalTrials.gov processed this record on July 20, 2014