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Hematologic MalignanciesPhase 1/2NCT00369226

Bortezomib Plus Tacrolimus and Methotrexate to Prevent Graft Versus Host Disease (GVHD) After Mismatched Allogeneic Non-Myeloablative Blood Stem Cell Transplantation

A Phase 1/2 study testing Bortezomib (Velcade), Tacrolimus and Methotrexate in people with Hematologic Malignancies, run by Dana-Farber Cancer Institute at 2 sites 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

The purpose of this study is to determine if Velcade (also known as bortezomib) can help prevent graft versus host disease (GVHD) developing after transplantation. This is done by using a combination of three immune suppressive medications: Velcade, tacrolimus and methotrexate. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hematologic Malignancies
What is being tested?
Bortezomib (Velcade), Tacrolimus and Methotrexate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
2 sitesUnited States
Study dates
Aug 2006to Sep 2011
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Patients with hematologic malignancies including myelodysplastic syndrome (MDS), who are at a high risk of complications after myeloablative transplantation
  • Patients have a donor (both related and unrelated) who are mismatched according to protocol criteria
  • 18 years of age or older
  • Performance status 0-2
  • Life expectancy of > 100 days
  • Female subject is either post-menopausal or sterilized or willing to use an acceptable form of birth control
  • Male subject agrees to use an acceptable form of birth control

Who cannot join

  • Evidence of HIV infection
  • Total bilirubin > 2.0mg/dl that is due to hepatocellular dysfunction
  • Aspartate aminotransferase (AST) > 90
  • Known active hepatitis B or C
  • Serum creatinine > 2.0
  • Greater than or equal to Grade 2 peripheral neuropathy within 21 days of enrollment
Show all 14Show fewer
  • Prior allogeneic stem cell transplant
  • Patients with myeloproliferative disease (e.g. myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia)
  • Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV hear failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Hypersensitivity to Velcade, boron or mannitol
  • Pregnant or breast feeding
  • Patient has received other investigational drugs 14 days before enrollment
  • Serious medical or psychiatric illness
  • Another active solid tumor malignancy at the time of study entry

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: Phase I/II Trial of Bortezomib (Velcade) in Addition to Tacrolimus and Methotrexate to Prevent Graft Versus Host Disease (GVHD) After Mismatched Allogeneic Non-Myeloablative Peripheral Blood Stem Cell Transplantation

The purpose of this study is to determine if Velcade (also known as bortezomib) can help prevent graft versus host disease (GVHD) developing after transplantation. This is done by using a combination of three immune suppressive medications: Velcade, tacrolimus and methotrexate. Stem cell transplantation is one of the options for patients with cancer of the blood or blood forming organs. Recently, allogeneic stem cell transplants have been performed using lower doses of chemotherapy and radiotherapy: non-myeloablative or "mini" transplants. GVHD is a significant problem that may occur even after "mini" transplantations. Information from other research studies, suggests that Velcade may help to reduce the risk of developing GVHD when given early after transplantation.

Read the detailed description
  • In this study we are looking for the highest dose of Velcade that can be given to people safely when given with tacrolimus and methotrexate. Not everyone who participates in the study will receive the same amount of the study drug. The dose the participant will receive depends upon the number of subjects enrolled on the study and how well they have tolerated their doses of the drug.
  • Before Transplant: In addition to the chemotherapy drugs, fludarabine and busulfex, for the participants non-myeloablative transplant, they will also start taking tacrolimus orally three days before their transplant.
  • After Transplant Medication: Methotrexate; Intravenously on days 1, 3, 6 \& 11 after transplant for a total of 4 doses. Tacrolimus; Continue taking orally once daily. Velcade: Intravenously on days 1, 4 \& 7 after transplant, a total of 3 doses. Filgrastim: Subcutaneous injection daily starting the day after transplant and continuing until the participant blood counts have recovered.
  • After Transplant Physical Exams \& Tests: Participants will have physical exams and blood tests every week for 1 month. After 1 month, a none marrow biopsy will be performed to look for evidence of the donor's cells in the participants bone marrow.
  • Following the 1 month period of time, participants will be seen every few weeks. Another bone marrow biopsy, as well as blood tests, will be taken 3-4 months after the transplant to review the disease status. At this point, participants will come into the clinic about every 3 months, or as determined by their physician for about one year.
  • While the study ends at 12 months after transplant, we would like to keep track of the participants medical condition for the rest of their life.
Being tested
Bortezomib (Velcade), Tacrolimus, Methotrexate, blood stem cell transplantation
Keywords
Velcade, Bortezomib, Allogeneic Stem Cell Transplant, GVHD
Medical subject headings
Hematologic Neoplasms

What participants receive

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

  • Bortezomib (Velcade)Drug

    Infusion for a total of 3 doses

  • TacrolimusDrug

    Taken until Doctor determines it is not necessary any more

  • MethotrexateDrug

    Infusion for a total of 4 doses

  • blood stem cell transplantationProcedure or surgery

    Allogeneic Non-myeloablative peripheral blood stem cell transplantation

Study groups in NCT00369226
Study groupRoleWhat they receive
Bortezomib/Tacrolimus/Methotrexate post HSCTExperimentalNot described
Receives: Drug: Bortezomib (Velcade); Drug: Tacrolimus; Drug: Methotrexate; Procedure: blood stem cell transplantation

What is being measured

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

  1. The Maximally Tolerated Dose (MTD) of Bortezomib (Velcade) That Can be Administered With Tacrolimus and Methotrexate After Mismatched Allogeneic Non-myeloablative Peripheral Blood Stem Cell (PBSC) Transplantation

    The MTD of bortezomib was evaluated at 3 dose levels:

    Dose level 1: 1.0 mg/m^2 Dose level 2: 1.3 mg/m^2 Dose level 3: 1.5 mg/m^2 Cohorts of 3-5 pts were enrolled at each dose level. At any dose level, if no DLT in the first 3, 4, or 5 pts, then dose escalation would occur.

    If 3 evaluable pts in cohort, and 1 of 3 experiences DLT then 2 additional pts treated at the same dose level. If >=1 of 2 additional pts experience DLT then previous dose level will be MTD. If no DLT in additional 2 pts then dose escalation will occur. If 4 evaluable pts in cohort, and 1 of the 4 experiences DLT then 1 additional pt treated at same dose level. If this additional pt experiences DLT then the previous dose will be declared to be the MTD. If additional pt does not experience DLT, then dose escalation will take place. If 5 evaluable pts in cohort, and 1 experiences DLT, then dose escalation will take place. If >=2 of first 3, 4, or 5 pts experience DLT then the previous dose will be declared MTD.

    Measured: by day 45 post PBSC infusion

  2. Successful Initial Engraftment by Day 45 Post Peripheral Blood Stem Cell (PBSC) Infusion and Administration of Bortezomib (Velcade), Tacrolimus and Methotrexate

    Percentage of participants who did not experience failure to engraft or relapse or death before assessment.

    Measured: by day 45 post PBSC infusion

  3. Incidence of Grade II-IV Acute Graft Versus Host Disease (GVHD) by Day 100.

    Measured: by day 100 after peripheral blood stem cell (PBSC) infusion

Secondary outcomes (3)

  1. Sustained Engraftment Following Transplant.

    As measured by median total donor chimerism at day 100.

    Measured: by day 100 post transplant

  2. Incidence of Chronic Graft Versus Host Disease (Chronic GVHD).

    Number of participants with chronic GVHD at 1 year post transplant.

    Measured: by 1 year after PBSC infusion

  3. Overall Survival and Progression-free Survival.

    Progression is defined as disease relapse or disease progression since transplant.

    Measured: by 1 year after PBSC infusion

Timeline

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

  1. First posted29 Aug 2006 (estimated)
  2. Study startAug 2006
  3. Primary completionJul 2010
  4. Study completionSep 2011

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 1/2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00369226
Sponsor's protocol ID
06-065
Other IDs
X05175
Status last verified
Jun 2013
First submitted
24 Aug 2006
Last updated
25 Jul 2013
Data monitoring committee
Yes

Publications

  • Koreth J, Stevenson KE, Kim HT, Garcia M, Ho VT, Armand P, Cutler C, Ritz J, Antin JH, Soiffer RJ, Alyea EP 3rd. Bortezomib, tacrolimus, and methotrexate for prophylaxis of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation from HLA-mismatched unrelated donors. Blood. 2009 Oct 29;114(18):3956-9. doi: 10.1182/blood-2009-07-231092. Epub 2009 Aug 27.

    PubMed 19713456

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Bortezomib (Velcade), Tacrolimus and Methotrexate in people with Hematologic Malignancies, run by Dana-Farber Cancer Institute at 2 sites 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 7 inclusion and 14 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 25 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

The Maximally Tolerated Dose (MTD) of Bortezomib (Velcade) That Can be Administered With Tacrolimus and Methotrexate After Mismatched Allogeneic Non-myeloablative Peripheral Blood Stem Cell (PBSC) Transplantation (time frame: by day 45 post PBSC infusion). The study lists 3 primary outcomes in all. 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 NCT00369226, 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 25 Jul 2013.

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