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Graft Versus Host DiseasePhase 1NCT01672229

Bortezomib in Patients With Chronic Graft Versus Host Disease

A Phase 1 study testing Bortezomib in people with Graft Versus Host Disease, run by Mehrdad Abedi, MD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will investigate whether bortezomib can control the immune system and can be used to treat GVHD. Bortezomib has been used with not too many serious side effects in patients with multiple myeloma who will undergo transplant and also for acute graft versus host disease. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Graft Versus Host Disease
What is being tested?
Bortezomib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
Jul 2012to 9 Apr 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Voluntary written informed consent
  • Female subject is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agree to completely abstain from heterosexual intercourse.
  • Male subjects, even if surgically sterilized must agree to 2 effective methods of contraception.
  • Patients with chronic GVHD that involves 3 or more organs or with a score of 2 or greater in any single organ based on NIH cGVHD grading
  • Any previous treatments for cGVHD (except study drug). Participants may have received study drug for other reasons besides cGVHD such as leukemia or solid tumor.
  • Except for steroid refractory or intolerant cases, participants must be receiving baseline systemic glucocorticoid therapy for cGVHD at study entry. The dose of steroids must be stable for 14 days prior to starting study drug.
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  • At the time of trial enrollment, participants may be receiving one or two other immunosuppressive therapies in addition to glucocorticoids.
  • Chronic GVHD manifestations that can be followed on physical or laboratory exam.
  • Age >18 years old
  • ECOG performance status < 2. Patients with ECOG performance status of 3 (defined as being capable of only limited self-care, confined to bed or chair more than 50% of waking hours) will also be eligible only if the lower performance status is judged to be directly related to steroid and/or cGVHD effects.
  • Myeloablative or non-myeloablative allogeneic hematopoietic cell transplant.

Who cannot join

  • Patients with irreversible damage as the only manifestation of chronic GVHD (irreversible contractures or sicca syndrome)
  • Active uncontrolled infection
  • Contraindications to administration of bortezomib
  • Relapsed disease or development of other malignancies
  • Laboratory parameters:
  • ANC <1 x 10^9/L Platelets < 50 x 10^9/L Bilirubin >1.5 upper limit of normal (ULN) when it is clearly not related to GVHD. EF <45% DLCO <45% Creatinine clearance <30 Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 5 × ULN
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  • Platelet count of <50 within 5 days before enrollment.
  • Absolute neutrophil count of <1000 within 5 days before enrollment.
  • Patient has > Grade 2 peripheral neuropathy
  • Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
  • Patient has hypersensitivity to bortezomib, boron, or mannitol.
  • Female subject is pregnant or lactating.
  • Female patients who are lactating or have a positive serum pregnancy test during the screening period, or a positive urine pregnancy test on Day 1 before first dose of study drug, if applicable.
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of 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.
  • Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
  • Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California Comprehensive Cancer Center

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: A Pilot Study Of Weekly Subcutaneous Bortezomib In Patients With Steroid-Refractory Or -Dependent Chronic Graft Versus Host Disease

This study will investigate whether bortezomib can control the immune system and can be used to treat GVHD. Bortezomib has been used with not too many serious side effects in patients with multiple myeloma who will undergo transplant and also for acute graft versus host disease.

Read the detailed description

Bone marrow transplantation offers great promise for the treatment of a variety of diseases, particularly hematological malignancies. The incidence of acute GVHD has significantly decreased due to significant improvements in human leukocyte antigen (HLA) matching of the donors and recipients, more efficient GVHD prophylaxis regimens and the use of reduced-intensity preparative regimen. However, cGVHD remains a significant cause for increased morbidity and mortality associated with allogeneic stem cell transplantation.

While many of the patients with cGVHD respond initially to higher doses of steroids, cGVHD usually relapses during or following steroid taper. Because of the significant impact of steroids on this patient population, there is an urgent need for medications to take the place of high dose steroid use in this patient population.

We hypothesize that bortezomib can modulate the immune system and can be used to treat GVHD. At the same time bortezomib post transplant can induce a graft versus leukemia or lymphoma effect. Bortezomib has been used with minimal toxicity in post transplant setting for patients with aggressive multiple myeloma and also for acute graft versus host disease.

Being tested
Bortezomib
Medical subject headings
Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BortezomibDrug

    Also called Velcade

    If improvements are seen at any dose level and patients have no DLTs, they will stay at their dose level until the end of the study. This is to avoid any possible toxicity while the patient is benefiting from their current dosing of bortezomib. If the continuous improvement in GVHD stalls at any point, or the GVHD progresses after the original improvement, while the dose level is maintained, then the dose will be increased to the next dose level. Patients will remain enrolled until exacerbation of the GVHD on increasing dose schedule or closure of the study. Clinical activity will be monitored every other week after the initiation of bortezomib until the study closes.

Study groups in NCT01672229
Study groupRoleWhat they receive
Dose-escalationExperimentalBortezomib starting dose is 0.2 mg/m2 subcutaneously which will be given weekly with incremental increase of 0.2 mg/m2 every other week, if no improvement is seen, and no dose limiting toxicities are observed to the maximum dose of 1.6 mg/m2. Bortezomib will be administered in the outpatient clinic.
Receives: Drug: Bortezomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of weekly bortezomib in patients with chronic graft versus host disease panobinostat in combination with cisplatin and pemetrexed

    Safety assessments will consist of monitoring and recording all adverse events and serious adverse events, the regular monitoring of hematology, blood chemistry, regular measurement of vital signs and the performance of physical examination. Safety will be assessed according to the NCI CTCAE v4.

    Measured: Up to 9 months

Secondary outcomes (2)

  1. cGVHD Response

    Specific events of interest are recurrence of GVHD and relapse of primary cancer as measured by clinical cGVHD staging system based upon specific signs, degree of organ involvement (mild, moderate, severe), laboratory data, and/or histopathological confirmation.

    Measured: Up to 9 months

  2. Role of bortezomib on induction of immune tolerance by performing correlative studies

    Seven -10 mL of whole blood will be collected at each timepoint.

    Measured: Up to 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Aug 2012 (estimated)
  2. Study startJul 2012
  3. Primary completion9 Apr 2018
  4. Study completion9 Apr 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01672229
Sponsor's protocol ID
334528
Other IDs
UCDCC#229, X05379
Status last verified
May 2020
First submitted
1 Aug 2012
Last updated
28 May 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Pai CC, Chen M, Mirsoian A, Grossenbacher SK, Tellez J, Ames E, Sun K, Jagdeo J, Blazar BR, Murphy WJ, Abedi M. Treatment of chronic graft-versus-host disease with bortezomib. Blood. 2014 Sep 4;124(10):1677-88. doi: 10.1182/blood-2014-02-554279. Epub 2014 Jul 9.

    PubMed 25009225

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bortezomib in people with Graft Versus Host Disease, run by Mehrdad Abedi, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of weekly bortezomib in patients with chronic graft versus host disease panobinostat in combination with cisplatin and pemetrexed (time frame: Up to 9 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01672229, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2020.

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