VELCADE as Maintenance Treatment in Patients With Multiple Myeloma Following Autologous Peripheral Blood Stem Cell Transplantation (PBSCT)

NCT ID: NCT00311337

Last Updated: 2006-04-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

61 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-10-31

Study Completion Date

2010-10-31

Brief Summary

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Protocol DSMM VIII is a multi-center, open-label study evaluating the safety and tolerability, as well as the efficacy, of maintenance treatment with VELCADE (bortezomib) in patients with multiple myeloma with detectable disease activity following tandem high-dose chemotherapy and autologous SCT. The time from SCT to the initiation of VELCADE treatment will be 3 to 6 months.

Detailed Description

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Protocol DSMM VIII is a multi-center, open-label study evaluating the safety and tolerability, as well as the efficacy, of maintenance treatment with VELCADE in patients with multiple myeloma with detectable disease activity following tandem high-dose chemotherapy and autologous SCT. The time from SCT to the initiation of VELCADE treatment will be 3 to 6 months.

The initial 11 patients entered into this trial will be treated at a dose level of 1.0 mg/m2 once weekly on 4 consecutive weeks followed by 2 weeks of rest. A total of 4 treatment cycles is planned.

An interim analysis for safety and tolerability will be performed after at least the first cycle of study drug has been completed. If the study treatment is found to be safe and no dose-limiting toxicity has occurred, the dose of VELCADE will be increased to 1.3 mg/m2 and another 11 patients will be treated at this dose level according to the treatment schedule as outlined above. The dose escalation to 1.3 mg/m2 will be performed without delay if no AE or SAE are reported to the principal investigator.

If the safety of a specific dose level is acceptable the efficacy of the maintenance treatment will be statistically evaluated. The treatment is considered to be efficacious if a minimum of 25% of all treated patients experience a success, considered as remission of their disease within 6 months after the end of VELCADE treatment. The therapy will be acceptable for further clinical studies if a minium of 25% successfully treated patients will be observed.

Under these assumptions in the first step of the optimal two step design (Simon 1989) 21 patients have to be treated. As patients included during phase I are included in the efficacy analysis, this means an additional 10 patients to be treated. If less than three patients were successfully treated defined as an improvement in the remission status, the study will be stopped, because the success rate is unacceptably low. If three or more of the 21 patients are successfully treated, another 29 patients will be included. At the end of the study the success rate will be evaluated. If 8 or more of the 50 patients were successfully treated the therapy will be acceptable for further studies.

Patients will be evaluated at scheduled screening and baseline visits. After providing written informed consent to participate in the study, patients will be screened for study eligibility during a screening period of 28 days. Baseline assessment consists of a detailed history of pre-existing diseases, blood tests including disease-specific markers such as ß2-microglobulin, IgG, IgA, IgM, immunofixation from blood and urine, serum free light chains, a bone marrow biopsy, a skeletal survey, an electrocardiogram and a chest X-ray.

The study drug will be administered in study centers only. Prior to each administration of study drug, a short medical history focusing on VELCADE-associated side effects will be performed as well as complete blood cell counts, kidney and liver function tests.

A visit on day 30 following the last administration of study drug for the final assessment of safety and tolerability is mandatory in all patients included in this protocol.

Serological myeloma specific markers (monoclonal immunoglobulin, serum free light chains and immunofixation from blood and urine) will be performed at weeks 6, 12, 18 and 24 and thereafter in 3 months intervals. Bone marrow biopsies will be performed when serological markers indicate complete remission or progression, a skeletal survey once a year during follow-up. During the study, disease will be assessed according to the EBMT/IBMTR/ABMTR criteria.

Safety will be evaluated by the occurrence of clinical and laboratory toxicities and changes from baseline in physical examination findings, vital signs, and, if applicable, chest X-ray and electrocardiogram findings. All patients will receive an aminobisphosphonate at 4 weekly intervals. Other disease-modifying treatment such as alpha interferon or pulsed corticosteroids are strictly prohibited.

Conditions

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Multiple Myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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bortezomib

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patient having received tandem transplants with high-dose melphalan and autologous PBSCT within 3-6 months prior to inclusion into this protocol
* Patients with measurable minimal residual disease (very good partial remission \[VGPR\]) or patients in partial remission (PR) or patients with stable disease (SD) at the time of inclusion in the study
* Patient must agree to participate in the study.
* Patient agrees to use an appropriate method of contraception.
* Willingness and ability to comply with the study protocol for the duration of the study

Exclusion Criteria

* Patient showing signs of disease progression
* Patient has a platelet count \< 100 x 10\^9/L within 14 days before enrollment.
* Patient has an absolute neutrophil count \< 1.0 x 10\^9/L within 14 days before enrollment.
* Patient has a calculated or measured creatinine clearance \< 30 mL/minute within 14 days before enrollment.
* Patient has \>= Grade 2 peripheral neuropathy within 14 days before enrollment.
* Patient has hypersensitivity to bortezomib, boron, or mannitol.
* Patient has received prior treatment with bortezomib
* Patient is pregnant or nursing
* Patient has received other investigational drugs within 14 days before enrollment
* Patient has progressive disease
* Patient has a Karnofsky performance status \< 60%
* Patient has a life expectancy of \< 3 months
* Patient has received disease modifying agents following autologous stem cell transplantation other than aminobisphosphonates such as interferon-alpha or glucocorticosteroids
* Patient currently enrolled in another clinical research study and/or receiving an investigational reagent for any reason.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Wuerzburg

OTHER

Sponsor Role lead

Principal Investigators

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Hermann Einsele, MD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Internal Medicine II, University of Wuerzburg, Klinikstr. 6-8, 97070 Wuerzburg

Hermann Einsele, MD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Internal Medicine, University of Wuerzburg

Locations

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Medizinische Univ.-Klinik Graz

Graz, , Austria

Site Status RECRUITING

Klin. Abt. für Onkologie, AKH Wien

Vienna, , Austria

Site Status RECRUITING

Dept. of Hematology/Oncology, Charité Berlin

Berlin, , Germany

Site Status RECRUITING

Dept. of Internal Medicine, Ludwig-Maximilian-University Munich

Munich, , Germany

Site Status RECRUITING

Dept. of Internal Medicine A, University Muenster

Münster, , Germany

Site Status RECRUITING

Dept. of Internal Medicine III, University of Ulm

Ulm, , Germany

Site Status RECRUITING

Dept. of Internal Medicine II, University of Wuerzburg

Würzburg, , Germany

Site Status RECRUITING

Regionalkrankenhaus Bozen

Bolzano, , Italy

Site Status RECRUITING

Countries

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Austria Germany Italy

Central Contacts

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Hermann Einsele, MD

Role: CONTACT

+49-931-20170011

Holger Hebart, MD

Role: CONTACT

+49 7071 2984477

Facility Contacts

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Werner Linkesch, MD

Role: primary

++43(0)316/385-4086

Johannes Drach, MD

Role: primary

Orhan Sezer, MD

Role: primary

030/450-513105

Christian Straka, MD

Role: primary

089/5160-2278

Martin Kropff, MD

Role: primary

Peter Liebisch, MD

Role: primary

0731/500-33809

Hermann Einsele, MD

Role: primary

+4993120170011

Paolo Coser, MD

Role: primary

0039/471/908807

Other Identifiers

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DSMM VIII

Identifier Type: -

Identifier Source: org_study_id