This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
John Koreth, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01323920
First received: March 24, 2011
Last updated: May 23, 2017
Last verified: May 2017
  Purpose

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 Intervention Phase
Leukemia Lymphoma Myelodysplastic Syndrome Drug: Bortezomib Drug: Tacrolimus Drug: Methotrexate Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by John Koreth, MD, Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • 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:
  • 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

  • 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.

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

Enrollment: 35
Study Start Date: May 2011
Study Completion Date: November 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01323920

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Principal Investigator: John Koreth, MBBS, DPhil Dana-Farber Cancer Institute
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: John Koreth, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01323920     History of Changes
Other Study ID Numbers: 11-007
Study First Received: March 24, 2011
Results First Received: February 14, 2014
Last Updated: May 23, 2017

Keywords provided by John Koreth, MD, Dana-Farber Cancer Institute:
Stem Cell Transplant
Allogeneic Transplant
Donors

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Methotrexate
Tacrolimus
Bortezomib
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
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

ClinicalTrials.gov processed this record on June 23, 2017