MINIALO-VELCADE2005: A Study of Bortezomib (Velcade) Treated Multiple Myeloma Patients Pre and Post Allogeneic Haematopoietic Progenitor Cell Transplant With no Myeloablative Conditioning

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by PETHEMA Foundation
Sponsor:
Information provided by (Responsible Party):
PETHEMA Foundation
ClinicalTrials.gov Identifier:
NCT00564200
First received: November 26, 2007
Last updated: November 19, 2013
Last verified: November 2013
  Purpose

The primary objective of this study is to analyze the efficacy of allogeneic bone marrow transplantation in a reduced-intensity manner combined with bortezomib in the treatment of multiple myeloma with bad prognosis, in order to evaluate the response and relapse rates


Condition Intervention Phase
Multiple Myeloma
Drug: Bortezomib
Drug: dexamethasone
Drug: Fludarabine
Drug: Melphalan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: MINIALO-VELCADE2005: A Phase II National, Open-label, Multicenter, no Controlled Study of Treated With Bortezomib (Velcade) Multiple Myeloma Patients Pre and Post Allogeneic Haematopoietic Progenitor Cell Transplant With no Myeloablative Conditioning

Resource links provided by NLM:


Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • Analyze the efficacy of allogeneic bone marrow transplantation in a reduced-intensity manner combined with bortezomib [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: November 2007
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Bortezomib

    PREACONDICIONAMIENTO:

    • 2 cycles of 21 days : Velcade days: 1, 4, 8 and 11
    • 1 cycle of 13 days : Velcade days 1, 4, 8 and 11

    ACONDICIONAMIENTO:

    - Day -2: Velcade

    POSTRANSPLANTATION:

    • 2 cycles of 21 days : Velcade days 1, 8 and 15
    • 5 cycles of 56 days : Velcade days 1, 8 and 15
    Drug: dexamethasone

    PREACONDICIONAMIENTO:

    - 2 cycles of 21 days : Dexamethasone: days 1-4 and 8-11

    Drug: Fludarabine

    ACONDICIONAMIENTO:

    - Days -9 al -5: Fludarabine

    Drug: Melphalan

    ACONDICIONAMIENTO:

    - Days -4 and -3: Melphalan.

Detailed Description:

Multiple Myeloma is a plasma cell disorder characterized by an uncontrolled proliferation of bone marrow plasma cells leading to skeletal destruction with bone pain, anemia, renal failure, hypercalcemia, recurrent bacterial infections and extramedullary plasmacytomas. It accounts for 1% of all malignancies and slightly more than 10% of hematologic malignancies, with an annual incidence of about four per 100.000. Although this disease is incurable with a median survival of about 3 years, remarkable treatment advances have been recently made, including high-dose therapy followed by stem cell rescue and, particularly, the introduction of novel promising agents with new mechanisms of action.

The treatment with alquilant agents, melphalan or cyclophosphamide combined with prednisone has a median of no more than 3 years survival rate in approximately 50%. The chemotherapy combination and high-dose dexamethasone increases response rate with minimal effects in survival benefit. The limited efficacy of conventional treatment produced the introduction of the high-dose therapy followed by a stem cells transplant in order to increase antitumoral effect and prolong disease-free overall survival.

This way, autologous stem cells transplant has turned into optimal treatment for patients younger than 65 years with myeloma. Nevertheless there is increasing evidence that it benefits only patients who showed complete disease remission after transplantation.

The transcendental factor that determines the CR post-transplantation achievement is the initial chemotherapy- sensitivity disease, measuring the rapidity and the grade of response (rapidity of maximum response assessment) and the pre-transplantation M protein level (i.e., the grade of response to the initial treatment).

On the other hand, the treatments with alquilant agents can impede the obtention of adequate numbers of stem cells that make impossible the autotransplantation practice. For this reason nowadays the treatments based on dexamethasone are used as initial chemotherapy.

However, these regimens and particularly AVD have less activity than alquilant agents treatment. Bortezomib has shown a fast antimyeloma activity (response after 1 or 2 cycles) in refractory patients, where myelosuppression and cellular injury are not observed.

Alternating bortezomib and dexamethasone as pre-transplant induction regimen would show the following advantages:

  1. a rapid and high effect raised by means of the use of two drugs with proven activity when they are administered separately,
  2. absence of stem cells injury,
  3. different toxicity types avoiding the habitual side effects because of the dexamethasone abuse, when this one is administered in every cycle as it happens in AVD type regimens.
  Eligibility

Ages Eligible for Study:   18 Years to 66 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion 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.
  • Age over 18 and under 67 years old.
  • Patient diagnosed with symptomatic Multiple Myeloma based on standard criteria with bad prognosis. This factor is associated with at least one of the clinical alterations defined as follows:

Patient who displayed a Monosomy of chromosome 13 or other adverse cytogenetic abnormality.

Patient in first relapse. Patient with relapsed multiple myeloma after autologous transplantation.

  • Patient has a ECOG performance status <= 2.
  • Patient has a life-expectancy >3 months.
  • Patients who are candidates for autologous transplantation.
  • Patients must have HLA-identical sibling donors.
  • Patient has the following laboratory values before Baseline visit:

Platelet count ≥ 30000/mm3 (transfusion allowed), hemoglobin ≥ 8 g/dl (transfusion allowed) and absolute neutrophil count (ANC) ≥ 0.750/mm3. Lower values are accepted if they are caused by bone marrow infiltration.

Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal. Alanine transaminase (ALT): ): ≤ 2.5 x the upper limit of normal. Total bilirubin: ≤1.5 x the upper limit of normal. Serum creatinine value ≤ 2mg/dl

Exclusion Criteria:

  • Patient present serious pathologies that make impossible chemotherapy treatments:

    1. Congestive heart failure, angina or heart attack during last 12 months.
    2. Uncontrolled arterial hypertension.
    3. Uncontrolled supraventricular arrhythmias during last 3 last months.
    4. Ventricular arrhythmia.
    5. Hepatic disease (Cirrhosis).
  • Patient has Grade 2 peripheral neuropathy within 14 days before enrollment.
  • Patient with serious psychiatric disorders that make impossible comply satisfactorily with the protocol requirements.
  • Personal medical history of neoplasia of other type, except: carcinoma in situ, other curatively treated malignancy in complete remission for more than 10 years.
  • Patient has hypersensitivity to bortezomib, boron or mannitol.
  • Fertile patient is not going to use a medical effective contraceptive method during the trial.
  • Patient has received other investigational drugs within 30 days before enrollment
  • Patient is known to be seropositive for the human immunodeficiency virus (HIV), Hepatitis B surface antigen-positive or active hepatitis C infection.
  • Patient had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV, heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  • Patient is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.
  • Patient participated in clinical study VISTA.
  • Pregnant or breast-feeding women.
  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: NCT00564200

Contacts
Contact: Blade Joan, Dr 34 93 227 54 00 jblade@clinic.ub.es

Locations
Spain
H. de la Santa Creu I Sant Pau Recruiting
Barcelona, Spain
H. Clinic I Provincial Recruiting
Barcelona, Spain
Instituto Catalán de Oncología Recruiting
Barcelona, Spain
H. de Jerez Recruiting
Jerez de la Frontera, Spain
H. Univ. Gregorio Marañón Recruiting
Madrid, Spain
H. Univ. La Princesa Recruiting
Madrid, Spain
H. 12 de Octubre Recruiting
Madrid, Spain
H. Univ. Morales Meseguer Recruiting
Murcia, Spain
H. Univ. Son Dureta Recruiting
Palma de Mallorca, Spain
H. Univ. de Salamanca Recruiting
Salamanca, Spain
Sponsors and Collaborators
PETHEMA Foundation
Investigators
Study Chair: Bladé Joan, Dr Hospital Clinic of Barcelona
  More Information

Additional Information:
No publications provided

Responsible Party: PETHEMA Foundation
ClinicalTrials.gov Identifier: NCT00564200     History of Changes
Other Study ID Numbers: 2005-004858-27
Study First Received: November 26, 2007
Last Updated: November 19, 2013
Health Authority: Spain: Ministry of Health

Keywords provided by PETHEMA Foundation:
Multiple Myeloma, transplant

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Fludarabine
Fludarabine phosphate
Melphalan
Alkylating Agents
Anti-Inflammatory Agents
Antiemetics
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on October 23, 2014