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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: high dose dexamethsone

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Goyang, Korea, Republic of
    • National Cancer Center
  • Hwasun, Korea, Republic of
    • Chonnam National University Hwasun Hospital
  • Incheon, Korea, Republic of
    • Gachon University Gill Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital
  • Seoul, Korea, Republic of
    • Seoul St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VAD; VAD : high dose dexamethasone -> response(CR, PR)-> VAD chemotherapy(vincristine + doxorubicin + dexamethasone)-> PBSC -> aSCT	Drug: high dose dexamethsone; high dose dexamethasone : 40mg/day , D1-D4, D9-D12, IV or PO, repeat every 21days for 2cycles
Experimental: PAD; PAD : high dose dexamethasone -> response(MR,NC,PD)-> PAD chemotherapy(bortezomib + doxorubicin + dexamethasone)-> PBSC -> aSCT	Drug: high dose dexamethsone; high dose dexamethasone : 40mg/day , D1-D4, D9-D12, IV or PO, repeat every 21days for 2cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
response of PAD/VAD chemotherapy	Assess the overall response of PAD/VAD chemotherapy and after ASCT	right after ASCT

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2008
• Primary Completion (Actual): December 31, 2014
• Study Completion (Actual): December 31, 2014

Study Registration Dates

• First Submitted: December 6, 2010
• First Submitted That Met QC Criteria: December 6, 2010
• First Posted (Estimate): December 7, 2010

Study Record Updates

• Last Update Posted (Actual): November 28, 2017
• Last Update Submitted That Met QC Criteria: November 26, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: 4-2009-0510