Trial Title:
Busulfan and Melphalan Conditioning in Multiple Myeloma
NCT ID:
NCT01923935
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Melphalan
Busulfan
Conditions: Keywords:
Multiple myeloma, busulfan, melphalan,transplantation
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Unknown status
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BUSULFEX®
Description:
BUSULFEX® 3.2 mg/kg/day iv once daily over 3 hours (day-6~day-4)
Arm group label:
BUSULFEX®, Alkeran®
Intervention type:
Drug
Intervention name:
Alkeran®
Description:
Alkeran® 70 mg/m2/day iv once daily over 30 minutes (day-3~day-2)
Arm group label:
BUSULFEX®, Alkeran®
Summary:
The purpose of this study is to determine whether intravenous busulfan and melphalan as a
conditioning regimen is effective in the treatment of multiple myeloma undergoing
autologous stem cell transplantation.
Detailed description:
Title
- A phase 2, open-label, prospective, multicenter study to evaluate the efficacy of
intravenous busulfan and melphalan as a conditioning regimen in patients with
multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT)
Principal Investigator
- Je-Jung Lee (Chonnam National University Hwasun Hospital)
Co-investigators
- Hyeon Seok Eom (National Cancer Center)
- Kihyun Kim (Samsung Medical Center)
- Chang Ki Min (Seoul St. Mary's Hospital)
- Soo Jung Kim (Severance Hospital)
- Sung Soo Yoon (Seoul National University Hospital)
- Jae Hoon Lee (Gachon University Gil Hospital)
- Yeung-Chul Mun (Ewha Womans University Mokdong Hospital)
Duration
- 2 years
Study phase
- Phase II
Patients
- Patients with multiple myeloma who undergo autologous stem cell transplantation
Objectives(end points)
- Primary objective:
1. Treatment response up to 2 months after ASCT
2. Safety and toxicity (frequency of grade 3 or worse toxicities) of the
conditioning regimen
- Secondary objective:
1. Progression free survival (PFS)
2. Overall survival (OS)
Total patients
- Initial 105 evaluable patients
- Complete Response (CR) rate of 200mg/m2 melphalan conditioning chemotherapy followed
by ASCT in patients with newly diagnosed MM was about 26% and CR rate of busulfan
and melphalan conditioning chemotherapy followed by ASCT in patients with newly
diagnosed MM was about 40%. If the CR rate of busulfan and melphalan conditioning
chemotherapy followed by ASCT is more than 40%, this combination will be accepted as
active conditioning regimen that may be worth for investigating in phase III trial.
But, if the CR rate of this regimen is lower than 26%, this has not a merit than
200mg/m2 melphalan conditioning 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=0.4, and a lower activity level, p0=0.26 and drop rate
0.1. Initially 44 patients will be accrued. If 13 or more CR rate were observed, the
trial will be continued. Accrual will be planned to a total of 105 patients, If
total 35 or more patients were assessed as CR, busulfan and melphalan conditioning
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 105
Treatment Schedule
- Busulfan 3.2 mg/kg/day iv once daily over 3 hours(day-6 ~ day-4)
- Melphalan 70 mg/m2/day iv once daily over 30 minutes(day-3 ~ day-1). If Creatinine
Clearance (mL/min) < 50, reduce to 50 mg/m2. If Creatinine Clearance (mL/min) < 30,
excluded from the this trial
Informed consent
- Written informed consent must be obtained before any study-specific screening
procedures are performed
Screening
- Baseline assessments should be made within 28 days before treatment start:
1. Demographic data (date of birth and sex)
2. Eastern Cooperative Oncology Group performance status
3. Vital signs and physical examination (including height, and weight)
4. Medical history (including previous diseases/treatments and concomitant
diseases/ treatments)
5. Hematology - complete blood counts with differential count examination
6. Serum electrolytes (Na, K, Cl, Ca, phosphorus)
7. Serum lactate dehydrogenase
8. Hepatitis B virus/hepatitis C virus/HIV serology (If serologic tests were
conducted within 6 months prior to screening, retests are not required)
9. Serum Beta2-microglobulin
10. Quantitative serum M-protein (Serum protein electrophoresis), including
immunofixation or immune electrophoresis
11. Quantitative urine M-protein in 24 hrs urine (Urine protein electrophoresis),
including immunofixation or immune electrophoresis
12. Serum free light chain assay
13. Creatinine clearance if increased serum creatinine
14. ECG
15. multigated radionuclide angiography or 2D ECHO
16. Chest X-ray, Radiographic skeletal survey including skull, pelvis, vertebral
column and long bones
17. Bone marrow aspiration and biopsy with chromosome study, and flow cytometry or
immunohistochemistry
Assessment
- Primary outcome measure
1. To evaluate the objective responses after ASCT, the guidelines from the
International Myeloma Working (IMW) Group uniform response criteria will be
used
2. Response Criteria for Multiple Myeloma the guidelines from the IMW Group
uniform response criteria + Add for criteria of near CR (Immunofixation
positive CR)
3. Serum free light chain study will be added at the every evaluation of response
4. To confirm the stringent complete response (sCR) after ASCT, flow cytometry or
immunohistochemistry will be used
5. NCI Common Toxicity Criteria for Adverse Effects version 4.0 will be used for
the examination of toxicities
- Secondary outcome measure
1. PFS will be defined from the time of ASCT to the time of first sign of disease
progression or death
2. OS will be defined as the period from the time of ASCT to the date of the last
follow-up or death from any cause
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients with a confirmed diagnosis of MM
- Symptomatic MM
- Age 20 - 65 years
- The MM patients who performed the stem cell collection with appropriate stem cell
counts, cluster of differentiation 34 positive cells more than 2 x 10^6 /kg
- Eastern Cooperative Oncology Group 0 - 2
- The MM patients who received induction chemotherapy regardless of types of induction
- Patient has measurable disease when the patients started the primary induction
therapy, defined as follows: Measurable disease is defined as serum M-protein more
than 1 g/dL, urine M-protein more than 200 mg/24 hours, or free light chain more
than 100 mg/L
- Adequate liver functions before ASCT Transaminase less than 3 x upper normal value
Bilirubin less than 2 x upper normal value
- Adequate hematological function - Platelet count more than 50,000 /microliter,
hemoglobin more than 8 g / dL but, Prior red blood cell transfusion or recombinant
human erythropoietin use is allowed, absolute neutrophil count more than 1,000 /
microliter
- Expected survival: 6 months or more
- Informed consent
Exclusion Criteria:
- Systemic amyloid light chain amyloidosis, smoldering multiple myeloma or monoclonal
gammopathy of undetermined significance
- Patient with plasma cell leukemia
- Patients who received an extensive radiation therapy within 4 weeks
- Patient is known to be Human Immunodeficiency Virus positive
- Patient has known clinically active Hepatitis B or C
- Pregnant or lactating women, women of childbearing potential not employing adequate
contraception
- Other serious illness or medical conditions Uncontrolled or severe cardiovascular
disease, including myocardial infarction, within 6 months of enrollment, New York
Heart Association Class III or IV heart failure, uncontrolled angina, clinically
significant pericardial disease, or cardiac amyloidosis History of significant
neurological or psychiatric disorders including dementia or seizures Active
uncontrolled infection Active ulcers detected at gastroscopy Other serious medical
illnesses
- Known hypersensitivity to any of the study drugs or its ingredients concomitant
administration of any other experimental drug under investigation, or concomitant
chemotherapy, hormonal therapy, or immunotherapy
Gender:
All
Minimum age:
20 Years
Maximum age:
65 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
National Cancer Center
Address:
City:
Goyang-si
Zip:
410-769
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Hyeon Seok Eom, M.D., Ph.D.
Phone:
82-31-920-2402
Email:
hseom@ncc.re.kr
Investigator:
Last name:
Hyeon Seok Eom, M.D., Ph.D.
Email:
Principal Investigator
Facility:
Name:
Gachon University Gil Hospital
Address:
City:
Namdong-gu
Zip:
405-760
Country:
Korea, Republic of
Status:
Not yet recruiting
Contact:
Last name:
Jae Hoon Lee, M.D., Ph.D.
Phone:
82-32-460-2186
Email:
jhlee@gilhospital.com
Investigator:
Last name:
Jae Hoon Lee, M.D., Ph.D.
Email:
Principal Investigator
Facility:
Name:
Chonnam National University Hwasun Hospital
Address:
City:
Hwasun-gun
Zip:
519-763
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Je-Jung Lee, M.D, Ph.D.
Phone:
82-61-379-7638
Email:
f0115@chonnam.ac.kr
Contact backup:
Last name:
Jae-Sook Ahn, M.D, Ph.D.
Phone:
82-61-379-7635
Email:
ahnjaesook@hanmail.net
Investigator:
Last name:
Je-Jung Lee, M.D., Ph.D.
Email:
Principal Investigator
Investigator:
Last name:
Deok-Hwan Yang, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Jae-Sook Ahn, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Sung-Hoon Jung, M.D.
Email:
Sub-Investigator
Facility:
Name:
Samsung Medical Center
Address:
City:
Gangnam-gu
Zip:
135-710
Country:
Korea, Republic of
Status:
Not yet recruiting
Contact:
Last name:
Kihyun Kim, M.D., Ph.D.
Phone:
82-2-3410-3459
Email:
kihyunk@skku.edu
Investigator:
Last name:
Kihyun Kim, M.D., Ph.D.
Email:
Principal Investigator
Facility:
Name:
Seoul National University Hospital
Address:
City:
Jongno-gu
Zip:
110-744
Country:
Korea, Republic of
Status:
Not yet recruiting
Contact:
Last name:
Sung Soo Yoon, M.D., Ph.D.
Phone:
82-2-2072-3079
Email:
ssysmc@snu.ac.kr
Investigator:
Last name:
Sung Soo Yoon, M.D., Ph.D.
Email:
Principal Investigator
Facility:
Name:
Ewha Womans University Mokdong Hospital
Address:
City:
Mokdong
Zip:
158-710
Country:
Korea, Republic of
Status:
Not yet recruiting
Contact:
Last name:
Yeung-Chul Mun, M.D., Ph.D.
Phone:
82-2-2650-2777
Email:
yeungchul@ewha.ac.kr
Investigator:
Last name:
Yeung-Chul Mun, M.D., Ph.D.
Email:
Principal Investigator
Facility:
Name:
Seoul St. Mary's hospital
Address:
City:
Seocho-gu
Zip:
137-701
Country:
Korea, Republic of
Status:
Not yet recruiting
Contact:
Last name:
Chang Ki Min, M.D., Ph.D.
Phone:
82-2-2258-6053
Email:
ckmin@catholic.ac.kr
Investigator:
Last name:
Chang Ki Min, M.D., Ph.D.
Email:
Principal Investigator
Facility:
Name:
Severance Hospital
Address:
City:
Seodaemun-gu
Zip:
120-752
Country:
Korea, Republic of
Status:
Not yet recruiting
Contact:
Last name:
Soo Jung Kim, M.D.
Phone:
82-2-2228-5487
Email:
ALVIN97@yuhs.ac
Investigator:
Last name:
Soo Jung Kim, M.D., Ph.D.
Email:
Principal Investigator
Start date:
January 2013
Completion date:
December 2015
Lead sponsor:
Agency:
Chonnam National University Hospital
Agency class:
Other
Collaborator:
Agency:
Korea Otsuka Pharmaceutical Co., Ltd.
Agency class:
Industry
Source:
Chonnam National University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT01923935
