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Bendamustine, Prednisone and Velcade® for First-line Treatment of Patients With Symptomatic Multiple Myeloma (BPV)

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ClinicalTrials.gov Identifier: NCT02237261
Recruitment Status : Active, not recruiting
First Posted : September 11, 2014
Last Update Posted : May 15, 2018
Sponsor:
Collaborators:
German Cancer Research Center
Janssen-Cilag International NV
Mundipharma Research GmbH & Co KG
inVentiv Health Clinical
Information provided by (Responsible Party):
Dr. Marc Raab, University Hospital Heidelberg

Brief Summary:
The purpose of this study is to improve efficacy of treatment for patients with newly diagnosed multiple myeloma who are not eligible for high-dose chemotherapy followed by autologous stem cell transplantation by Bendamustin, Bortezomib (Velcade), and Prednisone.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Bendamustine, Bortezomib, Prednisone Phase 2

Detailed Description:
  1. Objectives Primary

    -Therapeutic efficacy of BPV regimen for multiple myeloma as evidenced by the overall response defined as partial response (PR) or better

    Secondary

    • to assess overall survival (OS) and progression-free survival (PFS)
    • to determine response duration
    • to investigate improvements of renal function
    • to evaluate safety and toxicity (with respect to adverse events of CTCAE grade ≧3 and SAEs)
    • to analyze the efficacy for genetically defined subgroups of myeloma patients based on iFISH and gene-expression profiling
  2. Investigational Medicinal Products Bortezomib Bendamustine both in combination with Prednisone

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bendamustine, Prednisone and Velcade® for First-line Treatment of Patients With Symptomatic Multiple Myeloma Not Eligible for High-dose Chemotherapy Followed by Autologous Stem Cell Transplantation (BPV).
Actual Study Start Date : November 2014
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : October 2018


Arm Intervention/treatment
Experimental: Bendamustine, Bortezomib, Prednisone
Induction: Bortezomib: 1.3 mg/m2 subcutaneous for 7 days and Bendamustine: 90 mg/m2 intravenous for 2 days and in addition Prednison: : 60 mg/m2 per os for 4 days Consolidation: Bortezomib: 1.3 mg/m2 subcutaneous for 4 days and Bendamustine: 90 mg/m2 intravenous for 2 days and in addition Prednison 60 mg/m2 per os for 4 days
Drug: Bendamustine, Bortezomib, Prednisone

Cycle 1 (d1-42) - Induction:

Bortezomib: 1.3 mg/m2 s.c.: d1, 4, 8, 11, 22, 25, 29, 32 Bendamustine: 90 mg/m2 iv, d1, 2 Prednison: : 60 mg/m2 po,, d1-4

Cycle 2-9 (d1-28) - Consolidation:

Bortezomib: 1.3 mg/m2 s.c.: d1, 8, 15, 22 Bendamustine: 90 mg/m2 iv: d1, 2 Prednison: 60 mg/m2 po: d1-4

Other Names:
  • Velcade (Bortezomib)
  • Levact (Bendamustine)




Primary Outcome Measures :
  1. Overall Response Rate (ORR) of BPV [ Time Frame: 2 years ]
    ORR is defined as PR or better


Secondary Outcome Measures :
  1. Number and percentage of patients achieving a complete response [ Time Frame: 2 years ]
    Number and percentage of patients achieving a complete response

  2. Progression-free survival (PFS) [ Time Frame: 2 years ]
    PFS defined as time from registration to progression or death whatever comes first

  3. Overall survival (OS) [ Time Frame: 2 years ]
    OS defined as time from registration to time of death from any cause.

  4. Time-to-progression (TTP) [ Time Frame: 2 years ]
    TTP defined as time from registration to disease progression. TTP is censored at time of deaths which are not caused by progression.

  5. Disease-free survival (DFS) [ Time Frame: 2 years ]
    DFS defined as time from start of CR to relapse or death from any cause whichever comes first. Patients evaluable for DFS are patients in complete Response.

  6. Duration of response (DOR) [ Time Frame: 2 years ]
    DOR defined as time from first observation of PR to the time of disease progression.

  7. Renal response according to IMWG (CRrenal, PRrenal, MRrenal) [ Time Frame: 2 years ]
    percent of patients with recovery/improvement of renal function (for patients with impared renal finction at baseline)

  8. Toxicity (with respect to adverse events of CTCAE grade ≧3 and SAEs) [ Time Frame: 2 years ]
    toxicity during study therapy with AE of CTC grade ≧ 3, as well as neuropathy of CTC grade 2, measured by CTC-AE (v4.0).

  9. Time to objective Response (TOR) [ Time Frame: 2 years ]
    TOR defined as time from registration to achieving an objective response for patients achieving an objective Response.

  10. Time to treatment failure (TTF) [ Time Frame: 2 years ]
    TTF is defined as time from registration to treatment discontinuation for any reason, including disease progression, Treatment toxicity, patient preference or death.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Newly diagnosed multiple myeloma requiring systemic treatment (according to CRAB criteria as specified in the appendix I) with following characteristics: Subject is not a candidate for high-dose chemotherapy and stem cell transplantation due to age, presence of comorbidities likely to have a negative impact on tolerability of HDT-SCT, or subject preference
  2. Measurable disease, defined as any quantifiable monoclonal protein value, defined by at least one of the following three measurements (Durie et al., 2006):

    • Serum M-protein ≥ 10g/l
    • Urine light-chain (M-protein) of ≥ 200 mg/24 hours
    • Serum FLC assay: involved FLC level ≥ 10 mg/dl provided sFLC ratio is abnormal
  3. Age>18 years
  4. WHO performance status 0-3 (WHO=3 is allowed only when related to MM and not to co-morbid conditions) (see appendix III)
  5. For women of childbearing potential: negative pregnancy test at inclusion
  6. All patients must be willing and capable to use adequate contraception during the complete therapy.
  7. All patients must agree to abstain from donating blood while on study
  8. Ability to understand character and individual consequences of the clinical trial
  9. Written informed consent (must be available before enrolment in the trial)

Exclusion Criteria:

  • Subjects presenting any of the following criteria will not be included in the trial

    1. Patient has known hypersensitivity to bortezomib, bendamustine and prednisone or to any of the constituent compounds (incl. boron and mannitol).
    2. Systemic AL amyloidosis (except for patients with AL amyloidosis of the skin or the bone marrow)
    3. Chemotherapy or radiotherapy during the past 5 years except patients with local radiotherapy in case of local myeloma progression. (Note: patients may have received a cumulative dose of up to 160 mg of dexamethasone or equivalent as emergency therapy within 3 weeks prior to study entry.)
    4. Plasma cell leukemia which requires the presence of 20% of plasma cell in peripheral blood leukocytes and at least 2 plasma cells/nl.
    5. Severe cardiac dysfunction (NYHA classification III-IV, see appendix III)
    6. Significant hepatic dysfunction (serum bilirubin ≥ 2 mg/dl or ASAT and/or ALAT ≥ 2.5 times normal level), unless related to myeloma
    7. Patients known to be HIV-positive
    8. Patients with active, uncontrolled infections
    9. Patients with peripheral neuropathy or neuropathic pain of CTC grade 2 or higher (as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0, see appendix V)
    10. Second malignancy during the past 5 years except:
  • Adequately treated basal cell or squamous cell skin cancer, or
  • Carcinoma in situ of the cervix, or
  • Prostate cancer < Gleason score 6 with undetectable prostate-specific antigen (PSA) over 12 months, or
  • Ductal breast carcinoma in situ with full surgical resection (i.e., negative margins), or
  • Similar malignant condition as a.- d. with an expected5-year disease free survival larger than 95% 11. Patients with acute diffuse infiltrative pulmonary and pericardial disease 12. Autoimmune hemolytic anemia with positive Coombs test or immune thrombocytopenia 13. Platelet count < 50 x 109/l (transfusion support within 14 days before the test is not allowed), unless related to myeloma 14. Hemoglobin < 7.5g/dl, unless related to myeloma 15. Absolute neutrophil count (ANC) < 0.75 x 109/l (the use of colony stimulating factors within 14 days before the test is not allowed), unless related to myeloma 16. Pregnancy and lactation 17. Participation in other clinical trials within one month prior to enrolment except for supportive care studies and vaccination studies. (Note: this does not include long-term follow-up periods without active drug treatment of previous studies during the last 6 months).

No subject will be allowed to enrol in this trial more than once.


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): NCT02237261


Locations
Germany
Mannheimer Onkologie Praxis
Mannheim, Ba-Wü, Germany, 68161
Hämatologisch-Onkologische gemeinschaftspraxis
Augsburg, Bayern, Germany, 86150
Gemeinschaftspraxis Dr. R. Schlag/Dr. B. Schöttker
Würzburg, Bayern, Germany, 97080
Onkologische Schwerpunktpraxis
Heidelberg, BW, Germany, 69115
Medizinische Klinik V, Universitätsklinikum Heidelberg, Sektion Multiples Myelom
Heidelberg, BW, Germany, 69120
Onkologische Schwerpunktpraxis Dr. G. Kojouharoff
Darmstadt, Hessen, Germany, 64295
Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanienkrankenhaus
Frankfurt, Hessen, Germany, 60389
Agaplesion Markus Krankenhaus gGmbH, Medizinisches Versorgungszentrum
Frankfurt, Hessen, Germany, 60431
Onkologisches Ambulanzzentrum Hannover am Diakoniekrankenhaus Henriettenstift gGmbH
Hannover, NRW, Germany, 30171
Onkologische Gemeinschaftspraxis
Köln, NRW, Germany, 50677
Klinikum Idar-Oberstein GmbH, Innere Medizin I
Idar-Oberstein, Rh-Pfalz, Germany, 55743
Onkologische Schwerpunktpraxis Speyer
Speyer, RP, Germany, 67346
Städtische Klinikum Dessau
Dessau, Sachsen-Anhalt, Germany, 06847
Klinikum Aschaffenburg, Med. Klinik II
Aschaffenburg, Germany, 63739
Onkologische Praxis Oldenburg/Delmenhorst
Oldenburg, Germany, 26121
Sponsors and Collaborators
University Hospital Heidelberg
German Cancer Research Center
Janssen-Cilag International NV
Mundipharma Research GmbH & Co KG
inVentiv Health Clinical
Investigators
Study Chair: Wolfgang Knauf, MD Hematology/Oncology,Bethanien hospital, Im Pruefling 17-19, 60389 Frankfurt/M., Germany

Responsible Party: Dr. Marc Raab, Marc S. Raab MD, Medical Hospital V (Hematology, Oncology, Rheumatology), Section multiple myeloma, University Hospital Heidelberg
ClinicalTrials.gov Identifier: NCT02237261     History of Changes
Other Study ID Numbers: BPV
2013-005485-19 ( EudraCT Number )
First Posted: September 11, 2014    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: May 2018

Keywords provided by Dr. Marc Raab, University Hospital Heidelberg:
Newly diagnosed symptomatic multiple myeloma

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
Prednisone
Bortezomib
Bendamustine Hydrochloride
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action