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

Multiple Myeloma Clinical Trial

— BPV  

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02237261
• Other study ID #: BPV
• Secondary ID: 2013-005485-19
• Status: Completed
• Phase: Phase 2
• Start date: November 2014
• Est. completion date: October 2018

Study information

• Verified date: October 2020
• Source: University Hospital Heidelberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: October 2018
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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

Locations

Country	Name	City	State
Germany	Klinikum Aschaffenburg, Med. Klinik II	Aschaffenburg
Germany	Hämatologisch-Onkologische gemeinschaftspraxis	Augsburg	Bayern
Germany	Onkologische Schwerpunktpraxis Dr. G. Kojouharoff	Darmstadt	Hessen
Germany	Städtische Klinikum Dessau	Dessau	Sachsen-Anhalt
Germany	Agaplesion Markus Krankenhaus gGmbH, Medizinisches Versorgungszentrum	Frankfurt	Hessen
Germany	Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanienkrankenhaus	Frankfurt	Hessen
Germany	Onkologisches Ambulanzzentrum Hannover am Diakoniekrankenhaus Henriettenstift gGmbH	Hannover	NRW
Germany	Medizinische Klinik V, Universitätsklinikum Heidelberg, Sektion Multiples Myelom	Heidelberg	BW
Germany	Onkologische Schwerpunktpraxis	Heidelberg	BW
Germany	Klinikum Idar-Oberstein GmbH, Innere Medizin I	Idar-Oberstein	Rh-Pfalz
Germany	Onkologische Gemeinschaftspraxis	Köln	NRW
Germany	Mannheimer Onkologie Praxis	Mannheim	Ba-Wü
Germany	Onkologische Praxis Oldenburg/Delmenhorst	Oldenburg
Germany	Onkologische Schwerpunktpraxis Speyer	Speyer	RP
Germany	Gemeinschaftspraxis Dr. R. Schlag/Dr. B. Schöttker	Würzburg	Bayern

Sponsors (5)

Lead Sponsor	Collaborator
University Hospital Heidelberg	German Cancer Research Center, inVentiv Health Clinical, Janssen-Cilag International NV, Mundipharma Research GmbH & Co KG

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Knauf W, Dingeldein G, Schlag R, Welslau M, Moehler T, Terzer T, Walter S, Habermehl C, Kunz C, Goldschmidt H, Raab MS; BPV trial group. First-line therapy with bendamustine/prednisone/bortezomib-A GMMG trial for non-transplant eligible symptomatic multip — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR) of BPV	ORR is defined as PR or better	2 years
Secondary	Number and percentage of patients achieving a complete response	Number and percentage of patients achieving a complete response	2 years
Secondary	Progression-free survival (PFS)	PFS defined as time from registration to progression or death whatever comes first	2 years
Secondary	Overall survival (OS)	OS defined as time from registration to time of death from any cause.	2 years
Secondary	Time-to-progression (TTP)	TTP defined as time from registration to disease progression. TTP is censored at time of deaths which are not caused by progression.	2 years
Secondary	Disease-free survival (DFS)	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.	2 years
Secondary	Duration of response (DOR)	DOR defined as time from first observation of PR to the time of disease progression.	2 years
Secondary	Renal response according to IMWG (CRrenal, PRrenal, MRrenal)	percent of patients with recovery/improvement of renal function (for patients with impared renal finction at baseline)	2 years
Secondary	Toxicity (with respect to adverse events of CTCAE grade ?3 and SAEs)	toxicity during study therapy with AE of CTC grade ? 3, as well as neuropathy of CTC grade 2, measured by CTC-AE (v4.0).	2 years
Secondary	Time to objective Response (TOR)	TOR defined as time from registration to achieving an objective response for patients achieving an objective Response.	2 years
Secondary	Time to treatment failure (TTF)	TTF is defined as time from registration to treatment discontinuation for any reason, including disease progression, Treatment toxicity, patient preference or death.	2 years

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