Standard of Care vs. Bortezomib in Graft-Versus Host Disease After Hematopoietic Stem Cell Transplant
Condition: Graft Versus Host Disease
MeSH terms: Graft vs Host Disease
Intervention: Tacrolimus; Methotrexate; Bortezomib; Sirolimus
Intervention MeSH terms: Sirolimus; Methotrexate; Bortezomib; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 138.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This research study is a Phase II clinical trial. Phase II clinical trials test the
      effectiveness of an investigational drug to learn whether the drug works in treating a
      specific cancer. "Investigational" means that the drug is still being studied and that
      research doctors are trying to find out more about it-such as the safest dose to use, the
      side effects it may cause, and if the drug is effective for treating different types of
      cancer. It also means that the FDA has not yet approved bortezomib to treat or prevent
      graft-versus-host disease. Bortezomib is approved by the FDA to treat other human
      malignancies.

      Bortezomib is a drug that has an anti-cancer effect that involves inhibiting cell growth and
      causing cell death. This drug has been used in other research studies, and information from
      thos other research studies suggests that bortezomib may help to lower the risk of GVHD after
      allogeneic stem cell transplantation in patients who have matched unrelated, unmatched
      related or unrelated donors in this research study.

      Allogeneic stem cell transplantation is a procedure in which selected blood cells taken from
      your sibling or unrelated donor are given to you. Lower doses of chemotherapy drugs are given
      before the donor cells are infused in a process known as reduced-intensity conditioning. Stem
      cell transplant destroys cancer in two ways: The conditioning regimen destroys cancer cells
      and teh immune cells from the donor can recognize cancer cells and kill them.

      A common problem after stem cell transplant is graft-versus-host disease (GVHD). The word
      "graft" refers to the donor blood cells that you will receive during your transplant. The
      word "host" refers to the person (in this case, you) receiving the cells. GVHD is a
      complication of transplantation where the donor graft attacks and damages some of your
      tissues. GVHD can cause skin rash, intestinal problems such as nausea, vomiting or diarrhea.
      GVHD may also damage your liver and cause hepatitis or jaundice. GVHD may also increase your
      risk of infection.

      After stem cell transplant, all patients receive prophylactic medications against GVHD. In
      this research study we are studying the safety and effectiveness of preventing GVHD using
      bortezomib treatment in combination with other drugs versus standard of care prophylaxis
      (tacrolimus + methotrexate). If you take part in this study, there is a 33% chance you will
      receive any one of the following GVHD prevention treatments:

        -  tacrolimus + methotrexate (standard of care GVHD prophylaxis)

        -  bortezomib + tacrolimus + methotrexate

        -  bortezomib + sirolimus + tacrolimus Sirolimus, tacrolimus and methotrexate are drugs
           that suppress the immune system to try to prevent GVHD.
    

Eligibility criteria:

        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