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: February 14, 2014
Last verified: February 2014
  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, Tacrolimus, Methotrexate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Cumulative Incidence of Grade II-IV Acute GVHD by Day 100 After Stem Cell Infusion [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To Assess Percentage Donor Engraftment by Day 30 Post Stem Cell Infusion [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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: 2 years ] [ Designated as safety issue: No ]
  • To Determine the Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression by 1 Year After Stem Cell Infusion [ Time Frame: 2 years ] [ Designated as safety issue: No ]

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, Tacrolimus, Methotrexate

Other Names:

Velcade Bortezomib 1.3 mg/m^2 IV Tacrolimus 0.05 mg/kg PO bid Methotrexate 15 mg/m^2 IV

Drug: Bortezomib, Tacrolimus, Methotrexate
Bortezomib 1.3 mg/m^2 IV Tacrolimus 0.05 mg/kg PO bid Methotrexate 15 mg/m^2 IV
Other Name: Velcade

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
Genders Eligible for Study:   Both
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

No publications provided

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: February 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
Stem Cell Transplant
Allogeneic Transplant
Donors

Additional relevant MeSH terms:
Leukemia
Lymphoma
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Methotrexate
Bortezomib
Tacrolimus
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents

ClinicalTrials.gov processed this record on July 23, 2014