An Open-Label Phase II Study of the Safety and Efficacy of Doxorubicin and Cyclophosphamide in Combination with Bortezomib, Lenalidomide, and Dexamethasone for Treatment of Patients with Newly Diagnosed Multiple Myeloma
- Conditions
- Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]Patients with newly diagnosed symptomatic multiple myeloma according to the International Myeloma Working Group Diagnostic Criteria (Kyle 2009)
- Registration Number
- EUCTR2011-002751-34-DK
- Lead Sponsor
- Vejle Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 35
Inclusion Criteria:
1.Male or female subjects ³ 18 years at the time of signing informed consent.
2.Subject is diagnosed with symptomatic multiple myeloma based on the International Myeloma Working Group Diagnostic Criteria (Kyle 2009):
a.Monoclonal plasma cells in the bone marrow =10% and/or presence of a biopsy-proven plasmacytoma.
b.Monoclonal protein present in the serum and/or urine. If no monoclonal protein is detected (non-secretory disease), then =30% monoclonal bone marrow plasma cells and/or a biopsy-proven plasmacytoma is required.
c.Myeloma-related organ dysfunction (1 or more)*:
o[C] Calcium elevation in the blood (Ionized serum calcium > 0.25 mmol/l above the upper limit of normal)
o[R] Renal insufficiency (Serum creatinine > 173 µmol/l)
o[A] Anemia (Hemoglobin < 6.0 mmol/l)
o[B] Lytic bone lesions or osteoporosis#
* A variety of other types of end-organ dysfunctions can occasionally occur and lead to a need for therapy. Such dysfunction is sufficient to support classification as myeloma if proven to be myeloma related.
# If a solitary (biopsy-proven) plasmacytoma or osteoporosis alone (without fractures) is the sole defining criteria, then =30% plasma cells are required in the bone marrow.
3.The myeloma disease burden must be measurable with at least one of the following criteria (Durie et al. 2006):
a.Serum M-protein = 10 g/l
b.Urine M-protein = 200 mg/24 h
c.Involved FLC = 100 mg/l provided serum FLC ratio is abnormal
d.Bone marrow plasma cells > 30%
4.Subject has a Karnofsky performance status of = 60 (Appendix 10).
5.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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
6.Subject is willing and able to comply with the protocol as judged by the investigator.
Are the trial subjects under 18? no
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
1.Any prior systemic therapy for multiple myeloma.
2.Other therapies such as biologic therapy and chemotherapy less than 3 months prior to screening.
3.Concurrent or recent (less than 2 weeks prior to Screening) radiotherapy or surgery.
4.Prior glucocorticoid treatment of multiple myeloma exceeding dexamethasone 20mg/day for a maximum of 7 days. Topical glucocorticosteroid therapy to treat non-malignant comorbid disorders is permitted.
5.More than or equal to grade 2 peripheral neuropathy according to the NCI-CTC criteria on clinical examination within 14 days before enrollment (Day 1 of Cycle 1).
6.Evidence of mucosal or internal bleeding and/or platelet counts < 50 x 109/l. Platelet transfusions may not be used to meet PLT eligibility criteria.
7.Absolute neutrophil count (ANC) < 1 x 109/l. Growth factors may not be used to meet ANC eligibility criteria.
8.Hemoglobin < 5.0 mmol/l. The subject may be included after correction of the hemoglobin level by transfusion or treatment with erythropoietin.
9.Alanine aminotransferase (ALAT) > 2 x ULN.
10.Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class IV heart failure (see Appendix 15), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
11.Clinically relevant active infection or serious co-morbid medical conditions, such as chronic obstructive or chronic restrictive pulmonary disease, and cirrhosis.
12.Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study.
13.Prior malignancy (within the last 3 years) except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer or other cancer for which the subject has been disease-free for at least 3 years.
14.Female subject is pregnant or breast-feeding. The first serum pregnancy test to be done within 10-14 days prior to the study treatment start and repeated serum pregnancy test to be done within 24 hours prior to the start of study treatment.
15.Female subjects who are of childbearing potential (biologically capable of becoming pregnant) or men with partners of childbearing potential, who are unwilling or unable to use effective means of contraception. The means of contraception must either commit to continued abstinence from sexual intercourse or begin TWO acceptable methods of birth control, one highly effective method (hormonal contraceptives pills, injections or implants, tubal ligation, partner’s vasectomy) and one additional effective method (condom, diaphragm, cervical cap) AT THE SAME TIME, at least 28 days before she starts ACVDL and for at least 28 days after the last dose of ACVDL.
16.Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
17.Uncontrolled diabetes mellitus at the discretion of the investigator.
18.Hypersensitivity and/or contraindication to any one of the Investigational Medicinal Products (IMP), acyclovir or similar anti-viral drug.
19.POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and ski
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method