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Standard of Care vs. Bortezomib in Graft-Versus Host Disease After Hematopoietic Stem Cell Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01754389
Recruitment Status : Completed
First Posted : December 21, 2012
Results First Posted : July 18, 2017
Last Update Posted : July 18, 2017
Information provided by (Responsible Party):
John Koreth, MD, Dana-Farber Cancer Institute

Brief 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.

Condition or disease Intervention/treatment Phase
Graft Versus Host Disease Drug: Tacrolimus Drug: Methotrexate Drug: Bortezomib Drug: Sirolimus Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 138 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2013
Actual Primary Completion Date : May 2016
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Bortezomib

Arm Intervention/treatment
Active Comparator: Arm A (Standard of Care)
Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously on days 1, 3, 6 and 11 post-transplant
Drug: Tacrolimus
Drug: Methotrexate
Experimental: Arm B (Experimental)
Bortezomib intravenously 1, 4 and 7 days post-transplant Tacrolimus intravenously and orally, Day -3 through 3-6 months post-transplant Methotrexate intravenously 1,3,6 and 11 days post-transplant
Drug: Tacrolimus
Drug: Methotrexate
Drug: Bortezomib
Experimental: Arm C (Experimental)
Bortezomib intravenously 1,4 and 7 days post-transplant Sirolimus, intravenously and orally, Day -3 through 3-6 months post-transplant Tacrolimus, intravenously and orally, Day -3 through 3-6 months post-transplant
Drug: Tacrolimus
Drug: Bortezomib
Drug: Sirolimus

Primary Outcome Measures :
  1. Percentage of Participants With Incidence of Grade II-IV GVHD [ Time Frame: 6 months ]
    The primary outcome of this study is the cumulative incidence of grade II-IV acute GVHD up to Day 180 after stem cell infusion. Acute GHVD is graded according to the modified Glucksberg criteria (adapted from Thomas et al., NEJM ,1975, pp. 895-90), which is based on criteria by which the provider classifies acute GVHD per its objective organ staging. Acute GVHD is assessed in weekly standard of care visits post stem cell infusion and is captured in the protocol EDC upon evaluation of clinical notes up to Day 100. Data for acute GVHD organ staging and etiologies are collected in an acute GVHD separate case report form and do not include system organ class, expectedness or attribution.

Secondary Outcome Measures :
  1. Percentage of Participants With Non-relapse Mortality [ Time Frame: 1 year ]
    Non-relapse mortality by 1 year after stem cell infusion.

  2. Percentage of Participants With Relapse [ Time Frame: 1 year ]
    Relapse relapse-cum-immunosuppression-free survival at 1 year after stem cell infusion

  3. Percentage of Participants With Progression-free and Overall Survival [ Time Frame: 1 year ]
    Progression-free and overall survival 1 year post stem cell infusion

  4. Percentage of Participants With Chronic Graft Versus Host Disease [ Time Frame: 1 year ]
    Rates of chronic GVHD 1 year after stem cell infusion

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01754389

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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Insitute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
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Principal Investigator: John Koreth, DPhil, MBBS Dana-Farber Cancer Institute
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: John Koreth, MD, Principal Investigator, Dana-Farber Cancer Institute Identifier: NCT01754389    
Other Study ID Numbers: 12-404
First Posted: December 21, 2012    Key Record Dates
Results First Posted: July 18, 2017
Last Update Posted: July 18, 2017
Last Verified: June 2017
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Calcineurin Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents