Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified March 2014 by Yonsei University.
Recruitment status was:  Recruiting
Sponsor:
Information provided by (Responsible Party):
Yonsei University
ClinicalTrials.gov Identifier:
NCT01255514
First received: December 6, 2010
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: high dose dexamethsone
Phase 2

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: 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

Resource links provided by NLM:


Further study details as provided by Yonsei University:

Primary Outcome Measures:
  • CR+near CR [ Time Frame: right after ASCT ] [ Designated as safety issue: No ]
    Assess the complete response (CR) + near CR (Immunofixation-positive CR) rate after autologous peripheral blood stem cell transplantation (ASCT)


Secondary Outcome Measures:
  • response of PAD/VAD chemotherapy [ Time Frame: right after ASCT ] [ Designated as safety issue: No ]
    Assess the overall response of PAD/VAD chemotherapy and after ASCT


Estimated Enrollment: 210
Study Start Date: October 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   20 Years to 65 Years   (Adult)
Genders Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01255514

Locations
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
Severance Hospital
Seoul, Korea, Republic of, 120-752
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
Sponsors and Collaborators
Yonsei University
  More Information

Responsible Party: Yonsei University
ClinicalTrials.gov Identifier: NCT01255514     History of Changes
Other Study ID Numbers: 4-2009-0510 
Study First Received: December 6, 2010
Last Updated: March 4, 2014
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

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
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
Vincristine
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on January 14, 2017