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A 3-Arm Randomized Phase II Study of Standard-of-Care vs. Bortezomib Based Graft-Versus-Host Disease Regimen for Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation Patients Lacking HLA-matched Related Donors


Phase 2
18 Years
75 Years
Open (Enrolling)
Both
Graft Versus Host Disease

Thank you

Trial Information

A 3-Arm Randomized Phase II Study of Standard-of-Care vs. Bortezomib Based Graft-Versus-Host Disease Regimen for Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation Patients Lacking HLA-matched Related Donors


You will undergo some screening tests or procedures to find out if you can be in this
research study. Many of these tests and procedures are likely to be part of regular cancer
care and may be done even if it turns out that you do not take part in the research study.
If you have had some of these tests or procedures recently, they may or may not have to be
repeated. Possible tests include a medical history, physical exam, laboratory tests,
pulmonary function tests, cardiac ejection fraction and a pregnancy test. If these tests
show that you are eligible to participate in the research study, you will begin the study
treatment. If you do not meet the eligibility criteria, you will not be able to participate
in the research study.

Because no one knows which of the study options is best, you will be "randomized" into one
of the study groups (described below). Randomization means that you are put into a group by
chance. It is like flipping a coin. You will have an equal chance of being placed in any of
the groups.

Before your transplant you will receiving conditioning therapy. The conditioning therapy for
this study involves fludarabine and busulfex. These drugs will be given five, four, three
and two days before your transplant (Days -5 through -2). Both these chemotherapy drugs are
commonly used in allogeneic stem cell transplantation. On Day 0, you will receive selected
blood cells taken from your sibling or unrelated donor.

You will receive 1 of 3 GVHD prophylaxis plans depending on which one you are randomized to:

- Group 1 will receive tacrolimus + methotrexate

- Group 2 will receive bortezomib + tacrolimus + methotrexate

- Group 3 will receive bortezomib + sirolimus + tacrolimus

Tacrolimus (Groups 1 and 2) will be started three days before your transplant (Day -3). You
will be given tacrolimus initially intravenously (through a needle in a vein in your arm or
through a "central line", a catheter or tube placed in the large vein under your collarbone
or your neck) and later by mouth. You will continue to take tacrolimus for 3 to 6 months
after your transplant. Your physician will discuss your tacrolimus dose with you.

Methotrexate (Groups 1 and 2) will be given intravenously one, three, six and eleven days
after your transplant (Days 1,3,6 and 11).

Bortezomib (Groups 2 and 3) will be given intravenously one, four and seven days after your
transplant (Days 1,4 and 7).

Sirolimus (Group 3 only) will start three days before your transplant (Day -3). You will be
given sirolimus initially intravenously and then later by mouth. You will need to continue
to take your sirolimus for 3 to 6 months after your transplant. Your physician will discuss
your sirolimus dose with you.

To help with engraftment, you will be given the drug G-CSF (Neupogen) starting the day after
your transplant, until your white blood cells recover. You will receive other medications as
part of standard of care to help prevent you from getting infections. You will also receive
medications to help prevent seizures during your conditioning therapy.

Each week for the first four weeks and 2,3,6 and 12 months following your transplant, you
will have a physical exam and you will be asked questions about your general health and
specific questions about any problems that you might be having and any medications you may
be taking. If you are taking bortezomib, you will have an exam and may be asked to fill out
an additional questionnaire about potential symptoms of numbness, tingling, weakness or pain
on days 1,4 and 7 after your transplant.

Each week for the first four weeks and 12 months following your transplant, you will have
blood drawn (approximately 6 teaspoons) to monitor your progress and health following
transplant. If you receive methotrexate and/or bortezomib, you will have an additional blood
draw on those days.

Approximately 12 months following your transplant, a needle will be inserted into your hip
bone and a small amount of bone marrow cells and a sample of bone are removed.


Inclusion Criteria:



- Histologically or cytologically confirmed advanced/aggressive hematologic malignancy
unlikely to be cured by alternative therapies

- HLA matched unrelated donors or 1-locus HLA mismatched related or unrelated donors

- Adequate organ function

- Willing to use appropriate contraception

Exclusion Criteria:

- Pregnant or breastfeeding

- Recipient of prior allogeneic hematopoietic stem cell transplantation

- Recipient of prior abdominal radiation therapy

- HIV positive on combination anti-retroviral therapy

- Seropositive for hepatitis B or C

- Known allergy to bortezomib, boron or mannitol

- Myocardial infarction within 6 months prior to enrollment or any other cardiac
dysfunction

- Uncontrolled infection

- Inability to withhold agents that may interact with hepatic cytochrome P450 enzymes
or gluthathione S-transferases

- Seizures or history of seizures

- Grade greater than or equal to 2 peripheral neuropathy within 21 days of enrollment

- Use of other investigational drugs within 21 days of enrollment

- History of another non-hematologic malignancy except if disease free for at least 5
years or cervical cancer in situ, or basal/squamous cell carcinoma of the skin

- Uncontrolled intercurrent illness

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine incidence of grade II-IV GVHD

Outcome Description:

To determine the incidence of grade II-IV acute GVHD by day 180 after stem cell infusion.

Outcome Time Frame:

6 months

Safety Issue:

No

Principal Investigator

John Koreth, DPhil, MBBS

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

12-404

NCT ID:

NCT01754389

Start Date:

January 2013

Completion Date:

Related Keywords:

  • Graft Versus Host Disease
  • Graft vs Host Disease

Name

Location

Brigham and Women's HospitalBoston, Massachusetts  02115
Dana-Farber Cancer InsituteBoston, Massachusetts  02115