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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01323920
First Posted: March 28, 2011
Last Update Posted: May 30, 2017
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.
Information provided by (Responsible Party):
John Koreth, MD, Dana-Farber Cancer Institute
March 24, 2011
March 28, 2011
February 14, 2014
March 31, 2014
May 30, 2017
May 2011
February 2013   (Final data collection date for primary outcome measure)
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.
To determine the incidence of grade II-IV acute GVHD by day 100 after stem cell infusion [ Time Frame: 2 years ]
Complete list of historical versions of study NCT01323920 on ClinicalTrials.gov Archive Site
  • 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 ]
  • To Assess Percentage Donor Engraftment by Day 30 Post Stem Cell Infusion [ Time Frame: 2 years ]
    To assess percentage donor engraftment by 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
  • To Assess Non-relapse Mortality, Progression-free and Overall Survival by 1 Year After Stem Cell Infusion [ Time Frame: 1 year ]
  • To determine the incidence of chronic GVHD requiring systemic immune suppression by 1 year after stem cell infusion [ Time Frame: 1 year ]
Not Provided
Not Provided
 
Bortezomib-based GVHD Prophylaxis After Allogeneic Transplant for Patients Without Matched Related Donors
Bortezomib-based Graft-Versus-Host-Disease Prophylaxis After Myeloablative Allogeneic Stem Cell Transplantation for Patients Lacking HLA-matched Related Donors: A Phase 2 Study

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.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndrome
  • 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
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

Interventions:
  • Drug: Bortezomib
  • Drug: Tacrolimus
  • Drug: Methotrexate
Koreth J, Kim HT, Lange PB, Bindra B, Reynolds CG, Chammas MJ, Armand P, Cutler CS, Ho VT, Glotzbecker B, Nikiforow S, Ritz J, Blazar BR, Soiffer RJ, Antin JH, Alyea EP 3rd. A Bortezomib-Based Regimen Offers Promising Survival and Graft-versus-Host Disease Prophylaxis in Myeloablative HLA-Mismatched and Unrelated Donor Transplantation: A Phase II Trial. Biol Blood Marrow Transplant. 2015 Nov;21(11):1907-13. doi: 10.1016/j.bbmt.2015.05.027. Epub 2015 Jun 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
35
November 2013
February 2013   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 60 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01323920
11-007
Yes
Not Provided
Not Provided
John Koreth, MD, Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
Not Provided
Principal Investigator: John Koreth, MBBS, DPhil Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP