UMIN-CTR Clinical Trial

Public title

Bortezomib with Dexamethasone compared with oral melphalan and predonisone pluse bortezomib in patients with refractory multiple myeloma: randomized phase 2 study

Acronym

PhaseII trial of bortezomib based regimen for multiple myeloma refractory to melphalan-predonine (MP) therapy-Tohoku Myeloma Treatment Organization TOMATO Study-

Scientific Title

Bortezomib with Dexamethasone compared with oral melphalan and predonisone pluse bortezomib in patients with refractory multiple myeloma: randomized phase 2 study

Scientific Title:Acronym

PhaseII trial of bortezomib based regimen for multiple myeloma refractory to melphalan-predonine (MP) therapy-Tohoku Myeloma Treatment Organization TOMATO Study-

Region

Japan

Condition

myeloma

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To evaluate safety and efficacy of bortezomib with dexamethasone and oral melphalan pluse predonisone(
MP therapy) with bortezomib in patients with MP therapy refractory(<PR) multiple myeloma:

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase II

Primary outcomes

Overall response rate

Key secondary outcomes

TTP
OS
PFS
CR rate
Time to response
Duration of response
Safety

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

YES

Concealment

No need to know

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Patients newly diagnosed multiple myeloma will receive melphalan and predonisolone(MP) for 3 cycles. MP therapy consists of oral administration of melphalan at 9mg/m2 on day 1-4 and oral predonisolone at 60mg/m2 on day1-4. Each cycle will be repeated for every 6 weeks. After 3 cycles, patients, whose response will be less than PR, will be randomly allocated to bortezomib with dexamethazone(BD) or MP pluse bortezomib(MPV).
BD arm consists with BD therapy and weekly BD therapy. In BD therapy, bortezomib 1.3mg/m2 will be administered intravenously on days 1, 4, 8, 11, 22, 25, 29, and 32. And dexamethasone 20mg/m2 will be administered on days 1, 2, 4, 5, 8, 9, 11, 12, 22, 23, 25, 26, 29, 30, 32, and 33.
In weekly BD therapy, bortezomib 1.3mg/m2 will be administered intravenously on days 1, 8, 22, and 29. And dexamethasone 20mg/m2 will be administered on days 1, 2, 8, 9, 22, 23, 29, and 30.
Patients will receive BD therapy for 2 cycles and weekly BD therapy for 5 cycles.
Each cycle will be repeated every 6 weeks

Interventions/Control_2

MPV arm consists with MPV therapy and weekly MPV therapy.
In MPV therapy, bortezomib 1.3mg/m2 will be administered intravenously on days 1, 4, 8, 11, 22, 25, 29, and 32 with MP therapy.
In weekly BD therapy, bortezomib 1.3mg/m2 will be administered intravenously on days 1, 8, 22, and 29 with MP therapy.
Each cycle will be repeated every 6 weeks

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.have given written informed consent.
2.have had diagnosis of symptomatic/non secretary myeloma by IMWG criteria. Or have had diagnosis of myeloma.
3.have measurable lesion.
Secretary type: have measurable serum M protein or urine M protein
Non secretary type: have measurable lesion > = 2.0 cm in major axes.
4.aged more than 65 years old or aged from 20 to 65 who cannot be candidate for autologous sten cell transplantation.
5.Performance status (ECOG) of 0 to 2
6.Refractory after 3 courses of MP therapy. Refractory is defined as patients whose response is less than PR.
7.Patients with adequately maintained organs functions.
A)T-bil, AST, ALT =< 2 times the upper limit of the institution's normal range.
B)WBC >= 3000/ul(neutrophil >= 1500/ul), PLT >= 50000/ul, Hb >= 8g/dl
C)ejection fraction >=50%
D)SatO2 >=94%
E)peripheral neuropathy =< grade 1

Key exclusion criteria

1.History of allergic reactions attributed to compounds described in this protocol.
2.History of allergic reaction attributed to bortezomib, mannitol, boron.
3.Active systemic infections requiring treatment.
4.Serious psychiatric illness.
5.Serious respiratory diseases or dysfunction.
6.Suspected with interstitial pneumonia by chest X-P or CT scan.
7.Serious cardiac dysfunction or required treatment.
8.Required hemodialysis not attribute to myeloma.
9.With plasma cell leukemia.
10.Pregnant or lactating.
11.ositive for HBs antigen, HCV antibody, or HIV antibody.
12.Otherwise judged by investigator to be unsuitable.

Target sample size

32

Name of lead principal investigator

1st name
Middle name
Last name	Hideo Harigae

Organization

Tohoku University Hospital

Division name

Hematology&Rheumatology

Zip code

Address

1-1 Seryou-machi, Aoba-ku, Sendai, Japan

TEL

022-717-7165

Email

harigae@med.tohoku.ac.jp

Name of contact person

1st name
Middle name
Last name	K Ishizawa

Organization

Tohoku University Hospital

Division name

Hematology&Rheumatology

Zip code

Address

1-1 Seryou-machi, Aoba-ku, Sendai

TEL

022-717-7165

Homepage URL

Email

kishizaw@med.tohoku.ac.jp

Institute

Deparment of Hematology&Rheumatology, Tohoku University Hospital

Institute

Department

Personal name

Organization

Ichinohazama Memorial READ BLOOD ACADEMY

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2010

Year

04

Month

09

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

No longer recruiting

Date of protocol fixation

2009

Year

05

Month

01

Day

Date of IRB

Anticipated trial start date

2009

Year

10

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2010

Year

04

Month

09

Day

Last modified on

2014

Year

04

Month

09

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000004198