Trial Outcomes & Findings for Bortezomib Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease (NCT NCT00815919)

Results Overview

Participants had their cGVHD evaluated per NIH consensus criteria: Complete response: resolution of all reversible manifestations of cGVHD. Partial response: a decrease ≥ 1 point on a 3-point organ-specific scale or 2 points or more on a 10-point global scale without progression in any organ sites. Stable disease: no evidence of cGVHD response without evidence of progressive cGVHD. Progressive cGVHD: increase of ≥ 1 point on an organ-specific 3-point scale, addition of a new immunosuppressive agent prior to the completion of 15 weeks of combination therapy, or requirement an increase in the total daily dose of corticosteroids above a participant's baseline corticosteroid dose during the 15-week combined treatment period. Mixed response: a response in primary sites of cGVHD involvement but interval progressive cGVHD in other organs or sites. Responses were not scored for oral or ocular cGVHD, since topical therapies were permitted during the study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Patients had their cGVHD assessed at Baseline and at 15 weeks or end of therapy

Results posted on

2015-07-22

Participant Flow

Participant milestones

Participant milestones
Measure	Velcade (Bortezomib) Prednisone : Taken orally once a day at a dose of 0.5-1 mg/kg. Dose reduction may be initiated after 1 cycle of therapy. A suggested taper is 10-25% every 1-2 weeks. Bortezomib : Given intravenously at a dose of 1.3 mg/m\^2 once a week for the first four weeks of a five week cycle for a total of 3 cycles
Overall Study STARTED	22
Overall Study COMPLETED	18
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Velcade (Bortezomib) Prednisone : Taken orally once a day at a dose of 0.5-1 mg/kg. Dose reduction may be initiated after 1 cycle of therapy. A suggested taper is 10-25% every 1-2 weeks. Bortezomib : Given intravenously at a dose of 1.3 mg/m\^2 once a week for the first four weeks of a five week cycle for a total of 3 cycles
Overall Study Unrelated Fungal Infection	1
Overall Study AML Relapse	1
Overall Study Lack of Efficacy	2

Baseline Characteristics

Bortezomib Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Velcade (Bortezomib) n=22 Participants Prednisone : Taken orally once a day at a dose of 0.5-1 mg/kg. Dose reduction may be initiated after 1 cycle of therapy. A suggested taper is 10-25% every 1-2 weeks. Bortezomib : Given intravenously at a dose of 1.3 mg/m\^2 once a week for the first four weeks of a five week cycle for a total of 3 cycles
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants
Age, Continuous	51 years n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants

PRIMARY outcome

Timeframe: Patients had their cGVHD assessed at Baseline and at 15 weeks or end of therapy

Participants had their cGVHD evaluated per NIH consensus criteria: Complete response: resolution of all reversible manifestations of cGVHD. Partial response: a decrease ≥ 1 point on a 3-point organ-specific scale or 2 points or more on a 10-point global scale without progression in any organ sites. Stable disease: no evidence of cGVHD response without evidence of progressive cGVHD. Progressive cGVHD: increase of ≥ 1 point on an organ-specific 3-point scale, addition of a new immunosuppressive agent prior to the completion of 15 weeks of combination therapy, or requirement an increase in the total daily dose of corticosteroids above a participant's baseline corticosteroid dose during the 15-week combined treatment period. Mixed response: a response in primary sites of cGVHD involvement but interval progressive cGVHD in other organs or sites. Responses were not scored for oral or ocular cGVHD, since topical therapies were permitted during the study.

Outcome measures

Outcome measures
Measure	Velcade (Bortezomib) n=20 Participants Prednisone : Taken orally once a day at a dose of 0.5-1 mg/kg. Dose reduction may be initiated after 1 cycle of therapy. A suggested taper is 10-25% every 1-2 weeks. Bortezomib : Given intravenously at a dose of 1.3 mg/m\^2 once a week for the first four weeks of a five week cycle for a total of 3 cycles
Overall Response Rate After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD Participants with a complete response in cGVHD	2 participants
Overall Response Rate After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD Participants with an partial response in cGVHD	14 participants
Overall Response Rate After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD Participants with stable cGVHD	1 participants
Overall Response Rate After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD Participants with progressive cGVHD	2 participants
Overall Response Rate After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD Participants with mixed response	1 participants

SECONDARY outcome

Timeframe: After 15 weeks of bortezomib plus prednisone therapy

Population: Of the overall 22 patients, 18 patients completed 3 cycles (15 weeks) of therapy

The participants' total daily steroid dose was recorded at baseline and after a 15 week course of treatment. Starting at a dose of 0.5-1 mg/kg, dose reduction of steroids was permitted after 1 cycle of therapy. The suggested taper was 10-25% every 1-2 weeks. .

Outcome measures

Outcome measures
Measure	Velcade (Bortezomib) n=18 Participants Prednisone : Taken orally once a day at a dose of 0.5-1 mg/kg. Dose reduction may be initiated after 1 cycle of therapy. A suggested taper is 10-25% every 1-2 weeks. Bortezomib : Given intravenously at a dose of 1.3 mg/m\^2 once a week for the first four weeks of a five week cycle for a total of 3 cycles
Proportion of Patients Tolerating >50% Steroid Dose Reduction After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD	14 participants

SECONDARY outcome

Timeframe: Toxicities were collected from the start of treatment through 15 weeks of therapy or end of study treatmetn

Participants' toxicities were graded based on the CTCAE version 3.0. The toxicities were then given an attribution to the velcade treatment: unrelated, unlikely, possible, probable, definite.

Outcome measures

Outcome measures
Measure	Velcade (Bortezomib) n=22 Participants Prednisone : Taken orally once a day at a dose of 0.5-1 mg/kg. Dose reduction may be initiated after 1 cycle of therapy. A suggested taper is 10-25% every 1-2 weeks. Bortezomib : Given intravenously at a dose of 1.3 mg/m\^2 once a week for the first four weeks of a five week cycle for a total of 3 cycles
The Toxicity of a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD Participants with >= Grade 3, unrelated/unlikely	7 participants
The Toxicity of a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD Participants with >= Grade 3, possible	1 participants
The Toxicity of a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD Participants with >= Grade 3, probable/definite	0 participants

SECONDARY outcome

Timeframe: 1 year after the start of study treatment

Population: Participants who were still being followed 1 year after the start of therapy.

Participants who were still being followed 1 year after the start of therapy had their prednisone dose recorded.

Outcome measures

Outcome measures
Measure	Velcade (Bortezomib) n=17 Participants Prednisone : Taken orally once a day at a dose of 0.5-1 mg/kg. Dose reduction may be initiated after 1 cycle of therapy. A suggested taper is 10-25% every 1-2 weeks. Bortezomib : Given intravenously at a dose of 1.3 mg/m\^2 once a week for the first four weeks of a five week cycle for a total of 3 cycles
Proportion of cGVHD Patients Requiring Prednisone by 1 Year After Therapy Participants still requiring prednisone	11 participants
Proportion of cGVHD Patients Requiring Prednisone by 1 Year After Therapy Participants off prednisone	6 participants

SECONDARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Velcade (Bortezomib) n=22 Participants Prednisone : Taken orally once a day at a dose of 0.5-1 mg/kg. Dose reduction may be initiated after 1 cycle of therapy. A suggested taper is 10-25% every 1-2 weeks. Bortezomib : Given intravenously at a dose of 1.3 mg/m\^2 once a week for the first four weeks of a five week cycle for a total of 3 cycles
Overall and cGVHD Progression-free Survival by 1 Year After Therapy 2-year Cum-incidence of Non-relapse mortality	14 percentage of participants Interval 3.0 to 31.0
Overall and cGVHD Progression-free Survival by 1 Year After Therapy 2-year Cum-incidence of malignant relapse	14 percentage of participants Interval 3.0 to 31.0
Overall and cGVHD Progression-free Survival by 1 Year After Therapy 2 year progression-free survival	73 percentage of participants Interval 49.0 to 87.0
Overall and cGVHD Progression-free Survival by 1 Year After Therapy 2-year Overall survival	73 percentage of participants Interval 49.0 to 87.0

Adverse Events

Velcade (Bortezomib)

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Velcade (Bortezomib) n=22 participants at risk Prednisone : Taken orally once a day. Dose reduction may be initiated after 1 cycle of therapy. A suggested taper is 10-25% every 1-2 weeks. bortezomib : Given intravenously once a week for the first four weeks of a five week cycle for a total of 3 cycles
Blood and lymphatic system disorders Relapse AML	4.5% 1/22 • Number of events 1
Infections and infestations Infection	4.5% 1/22 • Number of events 1

Other adverse events

Other adverse events
Measure	Velcade (Bortezomib) n=22 participants at risk Prednisone : Taken orally once a day. Dose reduction may be initiated after 1 cycle of therapy. A suggested taper is 10-25% every 1-2 weeks. bortezomib : Given intravenously once a week for the first four weeks of a five week cycle for a total of 3 cycles
Metabolism and nutrition disorders Hyperglycemia	13.6% 3/22 • Number of events 4
Respiratory, thoracic and mediastinal disorders Hypoxia	4.5% 1/22 • Number of events 1
Renal and urinary disorders Renal Failure	4.5% 1/22 • Number of events 1
Nervous system disorders Neuropathy- sensory	4.5% 1/22 • Number of events 1
Metabolism and nutrition disorders ALT-SGPT elevated	9.1% 2/22 • Number of events 2
Metabolism and nutrition disorders AST-SGOT elevated	9.1% 2/22 • Number of events 2
Metabolism and nutrition disorders Alkaline Phosphotase elevated	4.5% 1/22 • Number of events 1

Additional Information

John Koreth, MBBS, DPhil

Dana-Farber Cancer Institute

Phone: 617-632-2949

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place