UMIN-CTR Clinical Trial

Public title

Safety and efficiency of modified-VMP schedule for patients with multiple myeloma who are not eligible for high-dose chemotherapy supported with autologous stem-cell trasplantation

Acronym

Osaka myeloma study group 2nd study (OMSG-2)

Scientific Title

Safety and efficiency of modified-VMP schedule for patients with multiple myeloma who are not eligible for high-dose chemotherapy supported with autologous stem-cell trasplantation

Scientific Title:Acronym

Osaka myeloma study group 2nd study (OMSG-2)

Region

Japan

Condition

multiple myeloma

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

In this study, we intend to explore an optimal VMP-treatment-schedule for Japanese patients with multiple myeloma who are not eligible for high-dose chemotherapy supported with autologous stem-cell transplantation. In the VMP-treatment schedule, bortezomib will be used subcutaneously, and the dose of therapeutic agents (bortezomib, melphalan, and predonisolone) will be less intensive than previous VMP schedule conducted in the foreign VISTA study.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Primary outcomes

Complete remission rate after 5 cycles of consolidation phase of this protocol (Maximum therapeutic results will be judged according to the International Myeloma Working Group Criteria.)

Key secondary outcomes

1. Complete remission rate after 9 cycles of consolidation phase of this protocol (Maximum therapeutic results will be judged according to the International Myeloma Working Group Criteria.)
2. Frequency and degree of adverse events
3. Completion rate of the protocol; Duration of the therapy (including maintenance-period)
4. Time to progression
5. Time to death
6. Cumulative dose and relative-dose-intensity of administered bortezomib

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

1. Induction phase (42 days): Bortezomib 1.3 mg/m2, subcutaneouslly (Days 1, 4, 8, 11, 22, 25, 29 and 32); Melphalan 0.18 mg/kg, orally (Days 1, 2, 3 and 4); Prednisolone 40 mg/m2, orally (Days 1, 2, 3 and 4).

2. Consolidation phase (35 days/cycle): Bortezomib 1.3 mg/m2, subcutaneously (Days 1, 8, 15 and 22); Melphalan 0.18 mg/kg, orally (Days 1, 2, 3 and 4); Prednisolone 40 mg/m2, orally (Days 1, 2, 3 and 4). This treatment will be repeated 6 to 9 cycles until cumulative dose of bortezomib reach to 40 mg/m2.

3. Maintenance phase (28 days/cycle): Bortezomib 1.3mg/m2, Day 1 or Days 1, 15, subcutaneously. (The maintenance phase can be implemented by the judgment of attending physicians.)

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1. Patients with multiple myeloma diagnosed from clinical manifestations, laboratory tests, or bone marrow aspiration.
2. Untreated patients having no history of pretreatment before enrollment (Local radiotherapy is not considered as a pretreatment).
3. Patients that attending physicians consider as ineligible for high-dose chemotherapy supported with autologous stem-cell transplantation at the time of initiation of induction therapy; Patients refusing to receive the high-dose chemotherapy.
4. Patients aged 20-year-old or above (At the time of registration)
5. Female patients who are not pregnant or may not become pregnant.
6. Patients accepting contraception by appropriate method during the therapy.
7. Patients without any history of hypersensitivity against bortezomib, mannnitol or boron.
8. Patients with ECOG Performance Status of 0 to 2
9. Patients without a serious and active infectious disease
10. Patients with sufficient major organ function (except the obstacles due to myeloma) for evaluating the safety and efficiency: Meeting all of the following criteria.
a. Neutorophil counts of 750/micro litter or above
b. Platelet counts of 50000/micro litter or above
c. PaO2 of 60mmHg or above; SaO2 of 93% or above
d. No grade 1 peripheral neuropathy with neuropathic pain; no peripheral neuropathy of Grade 2 or more
e. Serum AST/ALT values of 3 times of the upper limit of the standard values in each institute or below
f. Serum total bilirubin values of 2 times of the upper limit of the standard values in each institute or below
g. LVEF of 50% or above
11. Patients who have been fully explained about the purpose and the procedures of the study by the provided Informed Consent Form and have agreed to participate the study from their own will.

Key exclusion criteria

1. Patients with psychiatric disorders or psychological symptoms that are seemed to provide some difficulties for their participation.
2. Patients with a history of pretreatment for myeloma
3. Patients having a serious active infection
4. Patients in whom some signs of interstitial pneumonia present or are suspected in their chest-imaging exams.
5. Patients who have or may have serious pulmonary dysfunction.
6. Patients who have or may have serious cardiac dysfunction.
7. Patients with serum AST/ALT values of greater than 3 times of the upper limit of the standard values in each institute.
8. Patients with serum total bilirubin values of greater than 2 times of the upper limit of the standard values in each institute.
9. Patient with some serious drug-hypersensitivity.
10. Patients who cannot make decisions by themselves
11. Patients who are considered as inappropriate for the registration by attending doctors.

Target sample size

30

Name of lead principal investigator

1st name	Satoru
Middle name
Last name	Kosugi

Organization

Toyonaka Municipal Hospital

Division name

Internal Medicine (Department of Hematology)

Zip code

5608565

Address

4-14-1, Shibahara-cho, Toyonaka, Osaka, Japan

TEL

+81-6-6843-0101

Email

kosugi-s@chp.toyonaka.osaka.jp

Name of contact person

1st name	Daisuke
Middle name
Last name	Haraga

Organization

Tonoyaka Municipal Hospital

Division name

the General Affairs Department

Zip code

560-8565

Address

4-14-1, Shibahara-cho, Toyonaka, Osaka, Japan

TEL

+81-6-6843-0101

Homepage URL

Email

hsoumu@city.toyonaka.osaka.jp

Institute

Toyonaka Municipal Hospital

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Department of Hematology and Oncology, Osaka University Hospital

Name of secondary funder(s)

None

Organization

Toyonaka municipal hospital

Address

4-14-1, Shibaharacho, Toyonaka, Osaka

Tel

+81-6-6843-0101

Email

hsoumu@city.toyonaka.osaka.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

市立豊中病院（大阪府）
大阪大学医学部附属病院（大阪府）
市立伊丹病院（兵庫県）
大阪府立成人病センター（大阪府）
大手前病院（大阪府）
市立吹田市民病院(大阪府）
住友病院(大阪府）
日生病院(大阪府）
箕面市立病院（大阪府）
市立池田病院(大阪府)
NTT西日本大阪病院(大阪府)

Date of disclosure of the study information

2013

Year

02

Month

19

Day

URL releasing protocol

None

Publication of results

Partially published

URL related to results and publications

None

Number of participants that the trial has enrolled

13

Results

13 patients enrolled. 46% of patients completed the protocol. 4 and 3 patients stopped the therapy due to AEs and PD/SD. 5 (83.3%) achieved VGPR, and no CR was observed. Grade 3 PN was in 3, and grade 1-2 (autonomic neuropathy) was in 2; Grade 3 skin eruption was in 2. The low completion rate was considered to be due to the adverse events. VMP protocol might be difficult to be completed in elderly patients.

Results date posted

2021

Year

03

Month

01

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Auto-transplant ineligible myeloma patients were enrolled. 13 patients were recruited from Jan/2013 to Dec/2014. The recruitment was stopped according to the scheduled deadline. Median age, 72.5 year old (70-80). M/F ratio was 7/6.

Participant flow

The VMP protocol was conducted as follows to the patients who agreed their participation.

Cycle 1 (6W): Induction phase
Bortezomib 1.3mg/m2 (sc)days 1, 4, 8, 11, 22, 25, 29, 32
Melphalan 0.18 mg/kg (p.o.) days 1-4
Prednisolone 40mg/m2 (p.o.) days 1-4

Cycle 2-10 (5w): 6-9 cycles Consolidation phase
Bortezomib　1.3mg/m2 (sc) days 1, 8, 15, 22
Melphalan　0.18mg/kg (p.o.) days 1-4
Prednisolone 40mg /m2 (p.o.) days 1-4

Adverse events

Peripheral neuropathy
Grade3 - 3 patients
(ileus 2, sensory neuropathy 1)
Grade1/2 -2 patients
(autonomic neuropathy)
One patient with pacemaker died with cardiac arrest during the therapy for ileus.

Skin eruption
Grade3 - 2 patients
The protocol stopped in one patient.
All the others showed slight or mild skin reaction to subcutaneous-use bortezomib.

Hematological toxicity
Grade3/4- 7 patients

Outcome measures

Major achievement goal was not achieved in any patient.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2012

Year

12

Month

12

Day

Date of IRB

2013

Year

01

Month

24

Day

Anticipated trial start date

2013

Year

01

Month

24

Day

Last follow-up date

2017

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2013

Year

02

Month

18

Day

Last modified on

2021

Year

03

Month

01

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011734