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Infliximab for the Prevention of Graft-versus-Host Disease Following Allogenic Hematopoietic Stem Cell Transplantation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Craig Hofmeister, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00201799
First received: September 12, 2005
Last updated: November 5, 2013
Last verified: November 2013
  Purpose

This study will evaluate the efficacy of infliximab in reducing the incidence of grade II-IV acute graft versus host disease by day +100 post-transplant in patients undergoing allogeneic hematopoietic stem cell transplant.


Condition Intervention Phase
Graft-Versus-Host Disease
Drug: Infliximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase II Trial of Infliximab for the Prevention of Acute Graft-versus-Host Disease Following Allogenic Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Evaluate efficacy of infliximab in reducing incidence of grade II-IV acute GvHD by day +100 post transplant in patients undergoing allogenic HCT and receiving standard cyclosporine and short course methotrexate GvHD prophylaxis. [ Time Frame: 2004-2008 ] [ Designated as safety issue: Yes ]
    • For matched related donor transplants, we will test the null hypothesis H0: p ≥0.40 versus the alternative H1: p≤0.20, where p is the probability of grade II-IV acute GvHD by day +100.
    • For matched unrelated donor transplants, we will test the null hypothesis H0: p≥0.70 versus the alternative H1: p≤0.50, where p is the probability of grade II-IV acute GvHD by day +100.


Secondary Outcome Measures:
  • Assess the effect of infliximab on treatment-related mortality at 100 days post-transplant and on the incidence and severity of regimen related toxicity, including veno-occlusive disease (VOD) of the liver and interstitial pneumonitis (IP). [ Time Frame: 2004-2008 ] [ Designated as safety issue: Yes ]
    • Describe the incidence of infections occurring during the first year post-transplant.
    • Assess the effect of infliximab on the incidence of chronic GvHD
    • Relapse rate of the primary hematological malignancy
    • Assess the effect of Infliximab on blocking the TNF response to the conditioning regimen, and on the changes in cytokines important in the pathogenesis of acute GvHD in the peritransplant setting.
    • Explore the relationship between TNF gene polymorphism on the efficacy of infliximab prophylaxis therapy in preventing acute GvHD.


Enrollment: 19
Study Start Date: February 2004
Study Completion Date: March 2008
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Infliximab

    A total of 6 doses of Infliximab will be administered as follows:

    Dose 1: 10 mg/kg IV one day prior to commencing the myeloablative preparative regimen Dose 2: 10 mg/kg IV on day 0 to be given after peripheral blood stem cell infusion Dose 3: 10 mg/kg IV on day +7 Dose 4: 10 mg/kg IV on day +14 Dose 5: 10 mg/kg IV on day +28 Dose 6: 10 mg/kg IV on day +42

    Other Name: (Remicade®, Centocor)
Detailed Description:

Rationale: Acute graft host disease (GvHD) remains a barrier to successful hematopoietic stem cell transplantation (HCT) used for the treatment of cancers in some patients. GvHD can result from a lack of compatibility between the donor and recipient. Research suggests another primary cause of GvHD comes from cytokines, or a substance produced by cells of the immune system that affect the immune response in both positive and negative ways. Infliximab is an antibody that directly targets the cytokine associated with GvHD. This study is building upon previous research to assess infliximab's ability to prevent GvHD after HCT.

Purpose: This study is evaluating the efficacy of infliximab in reducing the incidence of GvHD after HCT. The safety of this approach, along with changes to specific cytokines from this treatment, will also be measured.

Treatment: Patients in this study will receive infliximab through intravenous infusion. Infliximab will be administered in six doses, including one day before chemotherapy or radiotherapy, after the stem cell infusion, and then on days 7, 14, 28 and 42. Standard post-transplant treatments of cyclosporine (Neoral) and methotrexate (Methotrexate) will also be given through intravenous infusion. Cyclosporine will be given on day 1, and the subsequent schedule will be determined on an individual basis. Methotrexate will be administered on days 1, 3, 6, and 11. Several tests and exams will be given throughout the study to closely monitor patients.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients undergoing allogeneic HCT for the following disorders:

    • Acute myelogenous leukemia
    • Acute lymphoblastic leukemia
    • Non-Hodgkin's lymphoma
    • Hodgkin's disease
    • Multiple myeloma
    • Chronic lymphocytic leukemia
    • Chronic myeloid leukemia in accelerated or blast crisis at time of transplant.
  • Age >20 yrs

Exclusion Criteria:

  • Patients undergoing allogeneic stem cell transplantation for chronic myelogenous leukemia and aplastic anemia are excluded.
  • Pregnant or breast-feeding females.
  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: NCT00201799

Locations
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Investigators
Principal Investigator: Craig Hofmeister, MD Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: Craig Hofmeister, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00201799     History of Changes
Other Study ID Numbers: OSU-0323
Study First Received: September 12, 2005
Last Updated: November 5, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio State University Comprehensive Cancer Center:
Hematopoietic Stem Cell Transplantation

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Infliximab
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Central Nervous System Agents
Dermatologic Agents
Gastrointestinal Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014