Study on the Reduction of Tumor Cell Burden With Bortezomib (Vel), Cyclophosphamide (C) and Dexamethasone (D) Before Stem Cell Transplantation (So-called Induction Therapy) in Patients With Multiple Myeloma Aged 60 Years or Less.
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Purpose
The purpose of this clinical study is to investigate induction therapy for remission with bortezomib, cyclophosphamide and dexamethasone in patients aged 60 years and younger with multiple myeloma planned for high-dose chemotherapy with stem cell transplantation.
| Condition | Intervention | Phase |
|---|---|---|
|
Multiple Myeloma Remission Induction Stem Cell Transplantation |
Drug: Cyclophosphamide (Cy) Drug: Bortezomib (Btz) Drug: Dexamethasone (D) |
Phase 2 Phase 3 |
| 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: | Phase II/III Study for Remission Induction With Bortezomib (Vel), Cyclophosphamide (C) and Dexamethasone (D) in Patients <= 60 Years With Untreated Multiple Myeloma and Planned High Dose Chemotherapy: (VelCD) |
- Efficacy (Response) [ Time Frame: efficacy of response after every one of three cycles ] [ Designated as safety issue: No ]
- Tolerability and comparison of response rates in different cytogenetic risk groups [ Time Frame: efficacy of response after every one of three cycles ] [ Designated as safety issue: Yes ]
| Enrollment: | 401 |
| Study Start Date: | March 2006 |
| Study Completion Date: | June 2009 |
| Primary Completion Date: | June 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 001
Bortezomib (Btz) Btz 1.3 mg/m2 intravenously Day 1,4,8,11 of each 21 day cycle for 3 cycles
|
Drug: Cyclophosphamide (Cy)
Cy 900mg as intravenous infusion on Day 1 of each 21 day cycle for 3 cycles
Drug: Bortezomib (Btz)
Btz 1.3 mg/m2 intravenously Day 1,4,8,11 of each 21 day cycle for 3 cycles
Drug: Dexamethasone (D)
D 40 mg tablet Days 1, 2, 4, 5, 8, 9, 11, 12 of each 21 day cycle for 3 cycles
|
Detailed Description:
Today high dose chemotherapy (HD-CT) with stem cell support is considered the standard for younger patients with multiple myeloma. The standard protocol for induction therapy before HD-CT is a combination therapy consisting of vincristine, adriamycin and dexamethasone. 40% of the patients do not respond to conventional induction therapy. With the combination of bortezomib and cyclophosphamide, a potent cytotoxic substance already in use against multiple myeloma, an increased efficacy is expected. In this prospective, open-label, single arm, multi-center study, induction therapy for remission with bortezomib, cyclophosphamide and dexamethasone in patients aged 60 years and younger with multiple myeloma planned for high-dose chemotherapy with stem cell transplantation is investigated. In the first part an evaluation of an optimal dose of cyclophosphamide if combined with a fixed bortezomib and dexamethasone dose is done and in the second part, efficacy and tolerance of the assessed dose is evaluated. Primary outcome of the second part is response prior to high dose chemotherapy. The first part (dose definition) has already been completed.On the days patients receive bortezomib, vital signs and blood tests and, at the first day of each cycle, a physical examination will be performed. Adverse events are to be documented and reported during the study in accordance with ICH-GCP guidelines. 400 male and female patients with untreated Multiple Myeloma are to be included in this study. In the first part of the study, the number of patients was restricted to 30. Thus, approximately 370 patients were to be included in the second part. Bortezomib 1,3 mg/m2 by intravenous bolus on Day 1, 4, 8, and 11 for a maximum of 3 cycles. One cycle consists of 21 days. Cyclophosphamide 900mg as intravenous infusion on Day 1 of each cycle. Dexamethasone 40 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle.
Eligibility| Ages Eligible for Study: | 18 Years to 60 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Multiple Myeloma stage II/III Durie and Salmon
- Patients without preceding cytostatic treatment, however, pretreatment with dexamethasone is allowed
- Written informed consent
- Female patients have to be postmenopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e.1 hormonal contraceptives, intrauterine device, diaphragm with spermicide, total abstinence or a vasectomised partner) during and 6 months after the treatment, pregnancy test has to be negative
- Male patients have to use an acceptable method of birth control during and 6 months after the treatment
- males should be offered sperm cryoconservation
- Karnofsky performance status >= 60%
- AST and ALT < 2.5 x the upper limit of normal (ULN)
- Bilirubin < 2.5 x the upper limit of normal (ULN)
- Adequate haematological parameters: leucocytes >= 3.0 x 109/l, neutrophils >= 1.5 x 109/l, platelets >= 75 x 109/l
- Creatinin < 2 x the upper limit of normal (ULN)
Exclusion Criteria:
- Non-secretory multiple myeloma
- known allergy or hypersensitivity to bortezomib, bor, mannitol, cyclophosphamide
- Estimated life expectancy less than 3 months
- History of cancer (except basal cell carcinoma) in the last 5 years
- Patients with history of peripheral neuropathy CTC grade >= 2
- Other severe illnesses that could potentially interfere with the completion of treatment according to this protocol: a. Insufficient liver or renal function, clinically relevant lung disease or gastrointestinal diseases, b. New York Heart Association (NYHA) > Class II heart failure, myocardial infarction within 6 months of enrollment, uncontrolled angina, severe uncontrolled ventricular arrhythmias (Lown IVB), electrocardiographic evidence of acute ischemia or active conduction system abnormalities, cardiac amyloidosis, c. Active systemic infection requiring treatment, d. Poorly controlled hypertension or vascular disease. Diabetes mellitus, or other serious endocrine or metabolic diseases
- Patients with hypotension (defined as RRsys sitting <= 100 mmHg and/or RRdia sitting <= 60 mmHg
- HIV positive patients
- Patients with active hepatitis B and/or C
- Pregnant or breast-feeding female patients
- Insufficient compliance, foreseeable follow-up problems, psychiatric diseases, known abuse of alcohol or drugs, legal incompetence
- Participation in another trial either parallel to this trial or within the last 30 days before enrollment into this trial
- except drug studies for relapse in the observation period.
Contacts and Locations More Information
No publications provided
| Responsible Party: | Medical Development Manager, Janssen-Cilag G.m.b.H. |
| ClinicalTrials.gov Identifier: | NCT00833560 History of Changes |
| Other Study ID Numbers: | CR005242 |
| Study First Received: | January 23, 2009 |
| Last Updated: | July 15, 2010 |
| Health Authority: | Germany: Federal Institute for Drugs and Medical Devices |
Keywords provided by Janssen-Cilag G.m.b.H:
|
Multiple myeloma Treatment Bortezomib Cyclophosphamide |
Dexamethasone Protease Inhibitors Induction therapy |
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 Cyclophosphamide |
Bortezomib Dexamethasone Dexamethasone acetate Dexamethasone 21-phosphate BB 1101 Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |
ClinicalTrials.gov processed this record on May 19, 2013