Evaluating the Efficacy and Safety of the Lower Dose of Bortezomib Plus Busulfan and Melphalan as a Conditioning Regimen in Patients With Multiple Myeloma Undergoing Autologous Peripheral Blood Stem Cell Transplantation- KMM103 Study

June 1, 2013 updated by: Yonsei University

A Phase 1/2, Open-label, Prospective, Multicenter Study to Evaluate the Efficacy and Safety of the Lower Dose of Bortezomib Plus Busulfan and Melphalan as a Conditioning Regimen in Patients With Multiple Myeloma Undergoing Autologous Peripheral Blood Stem Cell Transplantation- KMM103 Study

Despite the advantages of autologous stem cell transplantation (ASCT) over conventional chemotherapy,1,2 the results of high-dose chemoradiotherapy in multiple myeloma (MM) are still unsatisfactory with a 6-year event free survival (EFS) of only 24%.

Based on existing data, bortezomib-containing regimens are currently accepted at many centers as an induction treatment option for patients with symptomatic MM, particularly if it is planned to offer subsequent high-dose therapy with ASCT. So we will use bortezomib-containing regimens as induction prior to this novel conditioning regimen. The objective of the present study is to compare the toxicity and therapeutic efficacy of a new high-dose regimen using dose-escalation of BOR, BU and MEL for ASCT in the Korean patients with MM. The patients should be treated with bortezomib-containing regimens as an induction therapy before ASCT. We will specifically analyze (i) the efficacy of the conditioning regimen in improving the pre-ASCT status, response rate (ii) engraftment and transplant-related mortality (TRM) and (iii) the impact on survival including progression-free survival (PFS) and overall survival (OS).

Triple combination of conditioning will enhance the response rate after ASCT, and will improve not only PFS, but also OS. We think that data from this study may further strengthen feasibility of BOR in conditioning prior to ASCT.

Study Overview

Study Type

Interventional

Enrollment (Anticipated)

53

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Goyang, Korea, Republic of
        • Recruiting
        • National Cancer Center
        • Contact:
          • Hyeon-Seok Eom, MD, Ph.D
          • Phone Number: 82-31-1588-8110
      • Incheon, Korea, Republic of
        • Recruiting
        • Gachon University Gill Hospital
        • Contact:
          • Jae-Hoon Lee, MD, Ph.D
          • Phone Number: 82-32-1577-2299
      • Seoul, Korea, Republic of
        • Recruiting
        • Asan Medical Center
        • Contact:
          • Chul-Won Suh, MD, Ph.D
          • Phone Number: 82-2-1688-7575
      • Seoul, Korea, Republic of
        • Recruiting
        • Seoul National University Hospital
        • Contact:
          • Sung-Soo Yoon, MD, Ph.D
          • Phone Number: 82-2-2072-2114
      • Seoul, Korea, Republic of, 120-752
        • Recruiting
        • Severance Hospital
        • Contact:
          • Jin-Seok Kim, MD, Ph.D
          • Phone Number: 82-2-2228-1972
      • Seoul, Korea, Republic of
        • Recruiting
        • Samsung Medical Center
        • Contact:
          • Ki-Hyun Kim, MD, Ph.D
          • Phone Number: 82-2-1599-3114
        • Contact:
          • Seok-Jin Kim, MD, Ph.D
          • Phone Number: 82-2-1599-3114
      • Seoul, Korea, Republic of
        • Recruiting
        • Seoul St. Mary's Hospital
        • Contact:
          • Chang-Ki Min, MD, Ph.D
          • Phone Number: 82-2-2258-6053
      • Seoul, Korea, Republic of
        • Recruiting
        • Ewha Womans University MokDong Hospital
        • Contact:
          • Yeong-Chul Mun, MD, Ph.D
          • Phone Number: 82-2-2650-5114

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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)
  • The MM patients with induction chemotherapy with bortezomib-containing regimens (bortezomib±steroid±adrimycin)
  • The MM patients who performed the peripheral blood stem cell collection and appropriate stem cell counts (CD34+ cells 2 x 106/kg).
  • Age 20-65 years
  • Performance status: ECOG (Eastern Cooperative Oncology Group) 0-2.
  • Patient has measurable disease, defined as follows: measurable disease is defined as serum M-protein ≥ 1 g/dL or urine M-protein ≥ 200 mg/24 hours when the patients started the primary induction therapy.
  • 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.
  • Expected survival 6 months
  • 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)
  • Patients who received an extensive radiation therapy within 4 weeks
  • 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. Active ulcers detected at gastroscopy v. 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Busulfan
Bortezomib i.v. 0.7, 1.0 and 1.3 mg/m²/day
Other Names:
  • VELCADE®
Active Comparator: Melphalan
Bortezomib i.v. 0.7, 1.0 and 1.3 mg/m²/day
Other Names:
  • VELCADE®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximally tolerated dose (Phase 1)
Time Frame: 28 days
28 days

Secondary Outcome Measures

Outcome Measure
Time Frame
CR and near CR (Phase 2)
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2010

Primary Completion (Anticipated)

December 1, 2014

Study Completion (Anticipated)

December 1, 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 (Estimate)

June 4, 2013

Last Update Submitted That Met QC Criteria

June 1, 2013

Last Verified

June 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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