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

Multiple Myeloma Clinical Trial

Official title:

Sequential High-dose Dexamethasone and Response Adopted PAD (Bortezomib, Adriamycin, Dexamethasone) or VAD (Vincristine, Adriamycin, Dexamethasone) Induction Chemotherapy Followed by High-dose Chemotherapy With Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma; Multicenter Phase 2 Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01255514
• Other study ID #: 4-2009-0510
• Status: Completed
• Phase: Phase 2
• First received: December 6, 2010
• Last updated: November 26, 2017
• Start date: October 30, 2008
• Est. completion date: December 31, 2014

Study information

• Verified date: November 2017
• Source: Yonsei University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 31, 2014
• Est. primary completion date: December 31, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• high dose dexamethsone
high dose dexamethasone : 40mg/day , D1-D4, D9-D12, IV or PO, repeat every 21days for 2cycles

Locations

Country	Name	City	State
Korea, Republic of	National Cancer Center	Goyang
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun
Korea, Republic of	Gachon University Gill Hospital	Incheon
Korea, Republic of	ASAN Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CR+near CR	Assess the complete response (CR) + near CR (Immunofixation-positive CR) rate after autologous peripheral blood stem cell transplantation (ASCT)	right after ASCT
Secondary	response of PAD/VAD chemotherapy	Assess the overall response of PAD/VAD chemotherapy and after ASCT	right after ASCT