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Bortezomib-based GVHD Prophylaxis After Allogeneic Transplant for Patients Without Matched Related Donors

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: NCT01323920
Recruitment Status : Completed
First Posted : March 28, 2011
Results First Posted : March 31, 2014
Last Update Posted : May 30, 2017
Information provided by (Responsible Party):
John Koreth, MD, Dana-Farber Cancer Institute

Brief Summary:

A common problem after stem cell transplant is graft-versus-host-disease (GVHD). GVHD is a complication of transplantation where the donor graft attacks and damages some of your tissues. After stem cell transplant, all patients receive prophylactic medications against GVHD.

In this research study, we are studying the safety and effectiveness of a bortezomib based GVHD prophylaxic drug combination in participants after myeloablative allogeneic stem call transplantation from a matched unrelated donor, mismatched related or unrelated donor.

Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Myelodysplastic Syndrome Drug: Bortezomib Drug: Tacrolimus Drug: Methotrexate Phase 2

Detailed Description:

Before your transplant you will receive conditioning therapy with fludarabine and busulfan given 7, 6, 5, and 4 days before your transplant. On day 0, you will receive selected blood cells taken from your sibling or unrelated donor.

You will receive 3 drugs for your GVHD prophylaxis:

Tacrolimus will be started 3 days before your transplant. It will be given intravenously and later by mouth. You will continue to take tacrolimus for 3 to 6 months after transplant.

Methotrexate will be given intravenously 1, 3, 6 and 11 days after your transplant.

Bortezomib will be given intravenously 1, 4, and 7 days after your transplant. On days 1, 4, 7, 30 and 3, 6 and 12 months after your transplant you will have a physical exam, blood work, and be asked to complete a questionnaire.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bortezomib-based Graft-Versus-Host-Disease Prophylaxis After Myeloablative Allogeneic Stem Cell Transplantation for Patients Lacking HLA-matched Related Donors: A Phase 2 Study
Study Start Date : May 2011
Actual Primary Completion Date : February 2013
Actual Study Completion Date : November 2013

Arm Intervention/treatment
Experimental: Velcade/Tac/MTX

Drug: Bortezomib. Other Names: Velcade. Bortezomib 1.3 mg/m^2 IV

Drug: Tacrolimus. Tacrolimus 0.05 mg/kg PO bid

Drug: Methotrexate. Methotrexate 15 mg/m^2 IV

Drug: Bortezomib
Bortezomib 1.3 mg/m^2 IV
Other Name: Velcade

Drug: Tacrolimus
Tacrolimus 0.05 mg/kg PO bid

Drug: Methotrexate
Methotrexate 15 mg/m^2 IV

Primary Outcome Measures :
  1. The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion [ Time Frame: Day 100 ]
    The primary outcome of this study is the cumulative incidence of grade II-IV acute GVHD up to Day 100 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. The Percentage Donor Engraftment up to Day 30 Post Stem Cell Infusion [ Time Frame: Day 30 ]
    To assess the percentage donor engraftment up to day 30 post stem cell infusion, defined as the first of 3 consecutive days tested of documented absolute netrophil count (ANC) >/= 500 cells/u/L

  2. The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion [ Time Frame: 1 year ]
    Progression free and overall survival by 1 year after stem cell infusion will be assessed using the method of Kaplan and Meier. Progression-free survival will be defined as the time from stem cell infusion to the time of disease progression or death from any cause. Overall survival will be defined as the time from stem cell infusion to the time to death from any cause. Patients will be censored at the time last documented alive. Cumulative incidence and Kaplan-Meier curves will be constructed as appropriate. Progression is defined per clinical presentation, not protocol specified, and vary per disease, e.g. blasts in bone marrow or peripheral blood for AML/MDS; lymphoma + on PET/CT re-staging etc.

  3. The Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression up to 1 Year After Stem Cell Infusion [ Time Frame: 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically or cytologically confirmed advanced and/or aggressive hematologic malignancy (including myelodysplastic syndrome) that is unlikely to be cured by alternative therapies
  • HLA-Matched unrelated donor; or 1-locus HLA-mismatched related or unrelated donor
  • ECOG performance status 0-2
  • Adequate organ function
  • Able to understand and willing to sign a written informed consent document
  • Agrees to practice adequate contraception per study requirements

Exclusion Criteria:

  • Pregnant or breastfeeding
  • Recipient of prior allogeneic or autologous stem cell transplantation
  • Prior abdominal radiation therapy
  • HIV-positive on combination antiretroviral therapy
  • Seropositive for hepatitis B or C
  • Allergies to bortezomib, boron, or mannitol
  • Myocardial infarction within last 6 months, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias
  • Uncontrolled bacterial, viral or fungal infections
  • Seizures or history of seizures
  • History of another non-hematologic malignancy unless disease-free for at least 5 years
  • 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): NCT01323920

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United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
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Principal Investigator: John Koreth, MBBS, DPhil 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: NCT01323920    
Other Study ID Numbers: 11-007
First Posted: March 28, 2011    Key Record Dates
Results First Posted: March 31, 2014
Last Update Posted: May 30, 2017
Last Verified: May 2017
Keywords provided by John Koreth, MD, Dana-Farber Cancer Institute:
Stem Cell Transplant
Allogeneic Transplant
Additional relevant MeSH terms:
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Myelodysplastic Syndromes
Bone Marrow Diseases
Hematologic 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