Clinical trial NCT00815919: Bortezomib Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease
Official title: A Phase II Trial of Bortezomib (Velcade) Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Graft Versus Host Disease
Keywords: cGVHD
Velcade
bortezomib
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Millennium Pharmaceuticals, Inc.
First posted: 2008-12-31
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to determine the effectiveness of bortezomib (Velcade) plus prednisone for treating chronic graft versus host disease (cGVHD) and the safety of this drug combination in this patient population. Chronic GVHD is a medical condition that may occur after allogeneic stem cell transplantation. The donor's immune system may recognize the participants body (the host) as foreign and attempt to "reject" it. Bortezomib has been used in other research studies, and information from those studies suggests that this drug may help to control the abnormal immune responses that underlie cGVHD.

Detailed description: * Each treatment cycle lasts five weeks, during which time participants will come to the clinic to receive bortezomib intravenously once a week for the first 4 weeks. Prednisone will be taken orally on a daily basis and dose reduction may be initiated after 1 cycle of therapy.
* During all treatment cycles, participants will have the following: physical exam and blood work. At the end of cycle 3 (week 15) the participants cGVHD will be evaluated. These assessments may include an eye examination, a skin examination, a pulmonary function test and/or, a flexion assessment test.
* Participants will receive 3 cycles of bortezomib.

Eligibility criteria: Inclusion Criteria:

* Recipients of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens
* 100 days or more past stem cell transplantation
* Recipients of matched or mismatched, related or unrelated adult donor stem cells
* Must have cGVHD requiring systemic therapy
* No addition or subtraction of other immunosuppressive medications. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug. However, if cGVHD occurs during a taper of immune suppression, the medication(s) may not be increased back up to therapeutic level, but will continue a the taper dose for the 15 week study duration
* Adequate bone marrow, hepatic and renal function as outlined in the protocol
* Does not require hemodialysis
* 18 years of age or older
* ECOG Performance Status of 0-2 or Karnofsky performance score of 70% or greater
* Life expectancy of more than 3 months

Exclusion Criteria:

* Systemic steroid therapy in the 4 weeks prior to enrollment
* Active malignant disease after transplantation. Complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy will not be considered in this category
* Active uncontrolled infection
* Peripheral neuropathy CTC Grade 1 (or greater) with pain in the 4 weeks before enrollment. Other neurological deficits must be reviewed with the study PI prior to study entry
* Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
* Hypersensitivity to bortezomib, boron, or mannitol
* Female subject is pregnant or breast-feeding
* Serious medical or psychiatric illness likely to interfere with participation in this clinical study

Primary outcomes:
measure: Overall Response Rate After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
timeFrame: Patients had their cGVHD assessed at Baseline and at 15 weeks or end of therapy
Secondary outcomes:
measure: Proportion of Patients Tolerating >50% Steroid Dose Reduction After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
timeFrame: After 15 weeks of bortezomib plus prednisone therapy
measure: The Toxicity of a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
timeFrame: Toxicities were collected from the start of treatment through 15 weeks of therapy or end of study treatmetn
measure: Proportion of cGVHD Patients Requiring Prednisone by 1 Year After Therapy
timeFrame: 1 year after the start of study treatment
measure: Overall and cGVHD Progression-free Survival by 1 Year After Therapy
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: John Koreth, MBBS, DPhil
role: PRINCIPAL_INVESTIGATOR
References: