Thymoglobulin, Sirolimus and Mycophenolate Mofetil for Prevention of Acute Graft-Versus-Host Disease (GVHD)

This study has been terminated.
(Halted due to high incidence of veno-oclusive disease of the liver.)
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00506948
First received: July 20, 2007
Last updated: January 7, 2014
Last verified: January 2014
  Purpose

The goal of this clinical research study is to learn if the combination of rabbit anti-thymocyte globulin (Thymoglobulin®), sirolimus (Rapamune®), and mycophenolate mofetil (Cellcept®) can help to prevent graft versus host disease (GVHD). The safety of this drug combination will also be studied.

Primary Objective: To determine efficacy and toxicity of a regimen of thymoglobulin, sirolimus and mycophenolate mofetil for prevention of acute GVHD after allogeneic stem cell transplantation from human leukocyte antigen (HLA) identical related or unrelated donors.

Secondary Objective: To assess engraftment, chronic GVHD, relapse and survival.


Condition Intervention Phase
Hematological Malignancies
Myelodysplastic Syndrome
Leukemia
Lymphoma
Drug: Mycophenolate Mofetil (MMF)
Drug: Thymoglobulin
Drug: Sirolimus
Procedure: Stem Cell Transplant
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: Thymoglobulin, Sirolimus and Mycophenolate Mofetil for Prevention of Acute GVHD Following Allogeneic Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Failure Rate [ Time Frame: Baseline to 100 days post transplant ] [ Designated as safety issue: No ]
    Efficacy failure defined as a participants who had either grade 3-4 acute graft-versus-host disease (aGVHD) or treatment related mortality (TRM) within 100 days post transplant. Failure Rate calculated as (# of failures) / (# participants evaluated). Physical exam and bloodwork every week (for the first 90-100 days after the transplant).

  • Number of Participants With Acute Graft-versus-host Disease (aGVHD) [ Time Frame: Baseline to 100 days post transplant ] [ Designated as safety issue: No ]
    Participants who had acute graft-versus-host disease (aGVHD) within 100 days post transplant. Physical exam and bloodwork every week (for the first 90-100 days after the transplant).


Enrollment: 13
Study Start Date: September 2006
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Thymoglobulin + Sirolimus + MMF
Thymoglobulin 1.5 mg/kg intravenous (IV) days -4, -3, -2, -1 before Stem Cell Transplant (Day 0); Sirolimus 6 mg IV on day -2 followed by 2 mg daily to maintain therapeutic levels and Mycophenolate Mofetil (MMF) 15 mg/kg IV or orally every 12 hours starting on day 0 until day+27.
Drug: Mycophenolate Mofetil (MMF)
15 mg/kg by vein or by mouth every 12 hours.
Other Names:
  • CellCept
  • MMF
Drug: Thymoglobulin
1.5 mg/kg by vein daily for 4 days
Other Names:
  • Antithymocyte Globulin
  • rATG
  • ATG
Drug: Sirolimus
6 mg daily by mouth for 1 day, followed by 2 mg daily for 1 day.
Other Name: Rapamune
Procedure: Stem Cell Transplant
Stem cell infusion on Day 0.
Other Names:
  • hematopoietic stem cell transplantation
  • HSCT
  • transplantation

Detailed Description:

Rabbit anti-thymocyte globulin (rATG), sirolimus, and mycophenolate mofetil (MMF) are all designed to prevent GVHD.

If you are found to be eligible to take part in this study, you will receive rATG through a needle in your vein over 3-4 hours on each of the 4 days before the stem cell transplant.

Beginning 2 days before the transplant, you will take sirolimus by mouth once per day. You will continue to receive sirolimus until 90 days after the transplant. Beginning on Day 60, you will start taking increasingly lower doses of the study drug. This is done so you can taper down slowly, and be off of the drug on Day 90.

Beginning on the day of the transplant, you will take MMF by mouth 2 times a day. You will continue to take MMF until 27 days after the transplant.

Every week (for the first 90-100 days after the transplant) you will have study visits. At this visit, you will have a physical exam. Blood (about 1-2 tablespoons) will be drawn for routine tests.

You will remain on study for up to 90 days after transplantation. You will be taken off study if intolerable side effects occur.

Starting on Day 90 after the transplant, you will continue to follow up with your transplant doctor at least every 3 months through 1 year after the transplant. During these visits you will have physical exams. Blood (about 1-2 tablespoons) will be drawn for routine tests. Your doctor may request additional testing.

This is an investigational study. RATG, sirolimus, and MMF are all FDA approved for their use in the transplantation of solid organs (like kidney and liver). All 3 drugs are commercially available. This particular combination and dose schedule is considered investigational. Up to 30 patients will take part in this study. All will be enrolled at M.D. Anderson.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with high risk hematological malignancies, including those with induction failure and after treated or untreated relapse. High risk hematological malignancies include: Acute myelogenous or lymphocytic leukemia with induction failure of after relapse, myelodysplastic syndrome of intermediate and high risk according to Greenberg criteria, chronic myelogenous leukemia in accelerated phase or blast crisis, non-Hodgkin's and Hodgkin's lymphoma with induction failure or relapse after chemotherapy and refractory or relapsed chronic lymphocytic leukemia.
  2. HLA-identical sibling or matched unrelated donor transplants not eligible for protocols of higher priority.
  3. Age 18-75 years.
  4. Bilirubin </=1.5 mg/dl, serum glutamic-pyruvic transaminase (SGPT) </= 200 IU/ml.
  5. Creatinine </=1.6 mg/dl.

Exclusion Criteria:

  1. Regimens including rituximab or alemtuzumab in the preparative regimen.
  2. Patients can not have received prior treatment with gemtuzumab.
  3. Planned conditioning chemotherapy for transplant can not include gemtuzumab.
  4. Planned conditioning chemotherapy for transplant can not include the busulfan and cyclophosphamide regimen.
  5. HIV seropositivity
  6. Uncontrolled infection, not responding to adequate antimicrobial therapy after 7 days of treatment. The protocol PI is the final arbiter of eligibility.
  7. Pregnancy
  8. Inability to sign consent.
  9. Patients who are past recipients of allogeneic or autologous stem cell transplants from any source.
  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: NCT00506948

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Amin Alousi, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00506948     History of Changes
Other Study ID Numbers: 2006-0435
Study First Received: July 20, 2007
Results First Received: January 7, 2014
Last Updated: January 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Hematological Malignancies
Myelodysplastic Syndrome
Graft Versus Host Disease
GVHD
Allogeneic Hematopoietic Stem Cell Transplantation
AHSCT
Leukemia
Lymphoma
T-Cells
Thymoglobulin
ATG
rATG
Rabbit Antithymocyte Globulin
Rapamune
Sirolimus
Mycophenolate Mofetil
Cellcept
MMF

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Neoplasms
Lymphoma
Leukemia
Syndrome
Graft vs Host Disease
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
Sirolimus
Mycophenolic Acid
Everolimus
Mycophenolate mofetil
Antilymphocyte Serum
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents

ClinicalTrials.gov processed this record on September 18, 2014