Bendamustine, Bortezomib (Velcade ®) and Prednisone (BVP) in Patients Newly Diagnosed Multiple Myeloma

Sponsor

PETHEMA Foundation (Other)

Overall Status

Completed

CT.gov ID

NCT01376401

Collaborator

Mundipharma Pharmaceuticals B.V. (Industry), Janssen-Cilag Ltd. (Industry)

Enrollment

Locations

Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This protocol corresponds to an open-label national phase II, multicenter, to assess efficacy (in terms of response rate and CR) and toxicity of bendamustine, bortezomib and prednisone (BVP) in 60 patients newly diagnosed MM. Patients in the absence of disease progression or unacceptable toxicity receive up to 9 cycles of BVP. The patients eligible for autologous transplant receive four cycles of BVP, hematopoietic stem cell collection and administration of two cycles BVP over followed by autologous transplant.

In addition to the overall response rates, will also be analyzed time to progression (TTP), progression-free survival (PFS) and overall survival.

Finally, the results will be compared with BVP with those obtained in 120 patients included in our protocol VMP GEM10MAS65.

Patients will be evaluated at scheduled visits up to 3 periods of study:

pretreatment, treatment and monitoring.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Bendamustine Drug: Velcade Drug: Prednisone	Phase 2

Detailed Description

Patients included in the study will receive a 6 week cycle consisting of Bendamustine administered IV at doses of 90 mg/m2 on days 1 and 4 of the first cycle and days 1 and 8 in subsequent cycles in combination with Bortezomib as a bolus dose of 1.3 mg/m2 on days 1, 4, 8, 11, 22, 25, 29 and 32, and oral prednisone at doses of 60 mg/m2, during the first four days of each cycle.

Then, patients will receive eight additional cycles of 5-week . The same pattern consisting of bendamustine and prednisone but bortezomib is administered as an intravenous bolus dose of 1.3 mg/m2 on days 1, 8, 15 and 22.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Study Start Date :

Jul 1, 2011

Actual Primary Completion Date :

Jun 1, 2014

Actual Study Completion Date :

Dec 1, 2015

Outcome Measures

Primary Outcome Measures

Efficacy in terms of response rate and complete response rate (CR and near CR) [1 year]

Secondary Outcome Measures

Safety in terms of toxicity [1 year]
Time to progresion [3 years]
Progresion free survival [2 years]
Global survival [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient age greater than or equal to 18 at the time of signing Informed consent
Patient who has voluntarily signed informed consent before conduct of the trial any evidence that is not part of care normal patients, with the knowledge of the patient that can leave the trial at any time he want
Patient able, in the opinion of the physician to comply with the visitation schedule and other requirements of the protocol
Patient newly diagnosed symptomatic multiple myeloma based on standard criteria and has not received any previous treatment of chemotherapy for MM.
Patients with newly diagnosed multiple myeloma, secretory, or oligosecretor or not secretor if it has soft tissue plasmacytomas.
Patients with non-secretory MM oligosecretor or without white tissue plasmacytomas be excluded to keep a group of patients with characteristics similar to the previous study with which we compare the results.
Patients with measurable disease, defined by the following criteria:

For MM secreting measurable disease is defined as any value quantifiable serum monoclonal protein (≥ 1g/dl) and where applicable, a light chain excretion in urine ≥ 200 mg/24 hours. For Multiple Myeloma oligosecretor or secreting measurable disease defined by the presence of soft tissue plasmacytomas (not bone) determined by clinical examination or radiographic methods (eg MRI, CT-Scan)

ECOG PS ≤ 2
Expectations of life than 3 months.
The patient has the following laboratory values within 28 days before the baseline visit:

Platelet count ≥ 100 x 109 / L, hemoglobin ≥ 8.0g/dL and absolute neutrophil count (ANC) ≥ 1.5 x 109 / L; allowed counts under if they are clearly due to a bone marrow infiltration by MM.

Corrected serum calcium <14mg/dL. Aspartate transaminase (AST) ≤ 2.5 x upper limit of normal(LSN) Alanine aminotransferase (ALT) ≤ 2.5 x ULN Total bilirubin within normal limits Serum creatinine <2 mg / dL

Patients of childbearing potential must use effective contraception during duration of the study and up to 6 months after completion of treatment

Exclusion Criteria:

Patient has previously received treatment for multiple myeloma with Pulse steroids except for some emergency that requires it before start of induction therapy, administration of bisphosphonates or radiation therapy, or analgesic due to the presence of plasmacytomas, which require it for some urgency.
Patients with non-measurable disease.
Patient with peripheral neuropathy grade ³ 2 within 14 days prior to its inclusion in the trial
Patients with hypersensitivity to bortezomib, boric acid, or bendamustine mannitol
Patient to be known carrier of the virus HIV (human immunodeficiency) surface antigen of hepatitis B virus or who has active infection virus hepatitis C.
Patient who has had a myocardial infarction within 6 months prior to inclusion in the clinical trial or has a functional class III or IV according to the New York Heart Association (NYHA) heart failure, uncontrolled angina, uncontrolled ventricular arrhythmias or acute ischemia detected electrocardiographically or conduction system disorders.
Patient who has received any investigational agent within 30 days prior their inclusion or is currently in another clinical trial or receiving any investigational agent
Patient undergoing major surgery within 30 days before inclusion in the study
Patient pregnant or breastfeeding
Patients with acute diffuse infiltrative pulmonary disease and / or disease pericardium
History of other malignancies after different myeloma (except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) to unless the patient is free of the disease beyond 5 years
Hypertension arterial or poorly controlled diabetes mellitus or any other disease severe organ involving an unreasonable risk to the patient
Any psychiatric disorder that interferes with comprehension of consent informed or prevent the normal discharge that requires participation in this trial
Patients with major psychiatric history.

Contacts and Locations

Locations

	Site	City	State	Country
1	Hospital Germans Trias i Pujol	Badalona	Barcelona	Spain
2	Hospital Clínic	Barcelona		Spain
3	Institut català d'Oncología	Barcelona		Spain
4	Hospital 12 de Octubre	Madrid		Spain
5	Hospital Clínico San Carlos	Madrid		Spain
6	Hospital Universitario de la Princesa	Madrid		Spain
7	Hospital Universitario Ramón y Cajal	Madrid		Spain
8	MD Anderson Internacional	Madrid		Spain
9	Hospital General Morales Messeguer	Murcia		Spain
10	Hospital Universitario Virgen de la Victoria	Málaga		Spain
11	Hospital Universitario Central de Asturias	Oviedo		Spain
12	Hospital Universitario Virgen del Rocío	Sevilla		Spain
13	Hospital Universitario La Fe	Valencia		Spain
14	Hospital Clinico Universitario Lozano Blesa	Zaragoza		Spain