Sequential High-dose Dexamethasone and Response Adopted PAD or VAD Induction Chemotherapy Followed by High-dose Chemotherapy With Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma
Conditions
Multiple Myeloma
Conditions: official terms
Multiple Myeloma - Neoplasms, Plasma Cell
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: high dose dexamethsone
Type: Drug
Overall Status
Recruiting
Summary
Complete Response (CR) plus near CR rate of VAD (Vincristine, Adriamycin, Dexamethasone) induction chemotherapy followed by ASCT in patients with newly diagnosed MM was about 50% and CR plus near CR rate of PAD (Bortezomib, Adriamycin, Dexamethasone) induction chemotherapy followed by ASCT in patients with newly diagnosed MM was about 60%. If the CR with near CR rate of sequential high-dose dexamethasone and response adopted PAD or VAD induction chemotherapy followed by ASCT is more than 60%, this combination will be accepted as active regimen that may be worth for investigating in phase III trial. But, if the CR with near CR rate of this regimen is lower than 50%, this has not a merit than VAD induction chemotherapy.

Based upon the above assumption, this trial was designed by using Simon's optimal two-stage testing procedure. Assuming a target level of interest, p1=0.6, and a lower activity level, p0=0.5. Initially 61 patients will be accrued. If 33 or more CR + near CR rate were observed, the trial will be continued. Accrual will be planned to a total of 190 patients. If total 106 or more patients were assessed as CR with near CR, sequential high-dose dexamethasone and response adopted PAD or VAD induction chemotherapy regimen will be accepted as active regimen. This design provides probability 0.05 of accepting drugs worse than p0 and probability 0.20 of rejecting drugs better than p1. If we assume that drop-out rate is 10%, total accrual patient will be 210.

Patient characteristics and toxicity will be evaluated by descriptive methods. Progression free survival and overall survival (median value, 95% confidence interval) will be calculated by Kaplan-Meier method.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 65 Years
Minimum Age: 20 Years
Gender: Both
Criteria: Inclusion Criteria:

- Patients with a confirmed diagnosis of multiple myeloma (MM)

- Symptomatic MM (multiple myeloma with related organ or tissue damage)

- Previously untreated

- Age 20-65 years

- Performance status: ECOG 0-2

- Patient has measurable disease, defined as follows: For secretory multiple myeloma, measurable disease is defined as any quantifiable serum M-protein value and, where applicable, urine light chain of ≥200 mg/24 hours.

- For oligo-secretory multiple myeloma, measurable disease is defined as quantifiable light chain paraprotein on serum free light chain assay.

- For non-secretory multiple myeloma, measurable disease is defined as presence of soft tissue plasmacytoma(s) as determined by clinical examination or radiographic examination such as CT scan and magnetic resonance imaging (MRI), etc.

- Cardiac ejection fraction ≥ 50 % as measured by MUGA or 2D ECHO without clinically significant abnormalities

- Adequate liver functions: Transaminase (AST/ALT) < 3 X upper normal value, Bilirubin < 2 X upper normal value

- Adequate hematological function: Platelet count ≥ 75 x 109/L, hemoglobin ≥ 8 g/dL, (Prior RBC transfusion or recombinant human erythropoietin use is allowed), absolute neutrophil count (ANC) ≥ 1.0 x 109/L

- A negative serum or urine pregnancy test prior to treatment must be available both for pre menopausal women and for women who are < 1 years after the onset of menopause.

- Informed consent

Exclusion Criteria:

- Systemic AL amyloidosis, smoldering multiple myeloma or MGUS

- Patient with plasma cell leukemia (> 20% plasma cells in the PB and an absolute plasma cell count of at least 2000/μL)

- Previous chemotherapy or radiotherapy for the treatment of MM

- Patient is known to be Human Immunodeficiency Virus (HIV) positive

- Patient has known clinically active Hepatitis B or C

- Previous renal transplantation

- Severe peripheral neuropathy (Grade 2 or higher as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0)

- Any other malignancies within the past 5 years except curatively treated non-melanoma skin cancer or in situ carcinoma of cervix uteri

- Pregnant or lactating women, women of childbearing potential not employing adequate contraception

- Other serious illness or medical conditions :

i. Uncontrolled or severe cardiovascular disease, including myocardial infarction, within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis ii. History of significant neurological or psychiatric disorders including dementia or seizures iii. Active uncontrolled infection (viral, bacterial or fungal infection) iv. Other serious medical illnesses

- Known hypersensitivity to any of the study drugs or its ingredients (i.e., hypersensitivity to compounds containing boron or mannitol)

- Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy.
Locations
National Cancer Center
Goyang, Korea, Republic of
Status: Recruiting
Contact: Hyeon Seok Eom, MD, Ph.D - 82-31-1588-8110
Chonnam National University Hwasun Hospital
Hwasun, Korea, Republic of
Status: Recruiting
Contact: Je-Jung Lee, MD, Ph.D - 82-62-220-5114
Gachon University Gill Hospital
Incheon, Korea, Republic of
Status: Recruiting
Contact: Jae-Hoon Lee, MD, Ph.D - 82-32-1577-2299
ASAN Medical Center
Seoul, Korea, Republic of
Status: Recruiting
Contact: Chul-Won Suh, MD, Ph.D - 82-2-1688-7575
Samsung Medical Center
Seoul, Korea, Republic of
Status: Recruiting
Contact: Ki-Hyun Kim, MD, Ph.D - 82-2-1599-3114
Seoul National University Hospital
Seoul, Korea, Republic of
Status: Recruiting
Contact: Sung-Soo Yoon, MD, Ph.D - 82-2-2072-2114
Seoul St. Mary's Hospital
Seoul, Korea, Republic of
Status: Recruiting
Contact: Chang-Ki Min, MD, Ph.D - 82-2-2258-6053
Severance Hospital
Seoul, Korea, Republic of
Status: Recruiting
Contact: Jin-Seok Kim, MD, Ph.D - 82-2-2228-1972
Start Date
October 2009
Completion Date
December 2014
Sponsors
Yonsei University
Source
Yonsei University
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page