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

Primary Purpose

Hematological Malignancies, Myelodysplastic Syndrome, Leukemia

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Mycophenolate Mofetil (MMF)

Thymoglobulin

Sirolimus

Stem Cell Transplant

About this trial

This is an interventional treatment trial for Hematological Malignancies focused on measuring 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

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
HLA-identical sibling or matched unrelated donor transplants not eligible for protocols of higher priority.
Age 18-75 years.
Bilirubin </=1.5 mg/dl, serum glutamic-pyruvic transaminase (SGPT) </= 200 IU/ml.
Creatinine </=1.6 mg/dl.

Exclusion Criteria:

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

Sites / Locations

UT MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Thymoglobulin + Sirolimus + MMF

Arm Description

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.

Outcomes

Primary Outcome Measures

Failure Rate

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)

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).

Secondary Outcome Measures

Full Information

NCT ID

NCT00506948

First Posted

July 20, 2007

Last Updated

September 1, 2020

Sponsor

M.D. Anderson Cancer Center

Collaborators

Genzyme, a Sanofi Company

1. Study Identification

Unique Protocol Identification Number

NCT00506948

Brief Title

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

Official Title

Thymoglobulin, Sirolimus and Mycophenolate Mofetil for Prevention of Acute GVHD Following Allogeneic Hematopoietic Stem Cell Transplantation

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Terminated

Why Stopped

Halted due to high incidence of veno-oclusive disease of the liver.

Study Start Date

September 2006 (undefined)

Primary Completion Date

October 2010 (Actual)

Study Completion Date

October 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematological Malignancies, Myelodysplastic Syndrome, Leukemia, Lymphoma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Thymoglobulin + Sirolimus + MMF

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Mycophenolate Mofetil (MMF)

Other Intervention Name(s)

CellCept, MMF

Intervention Description

15 mg/kg by vein or by mouth every 12 hours.

Intervention Type

Drug

Intervention Name(s)

Thymoglobulin

Other Intervention Name(s)

Antithymocyte Globulin, rATG, ATG

Intervention Description

1.5 mg/kg by vein daily for 4 days

Intervention Type

Drug

Intervention Name(s)

Sirolimus

Other Intervention Name(s)

Rapamune

Intervention Description

6 mg daily by mouth for 1 day, followed by 2 mg daily for 1 day.

Intervention Type

Procedure

Intervention Name(s)

Stem Cell Transplant

Other Intervention Name(s)

hematopoietic stem cell transplantation, HSCT, transplantation

Intervention Description

Stem cell infusion on Day 0.

Primary Outcome Measure Information:

Title

Failure Rate

Description

Time Frame

Baseline to 100 days post transplant

Title

Number of Participants With Acute Graft-versus-host Disease (aGVHD)

Description

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).

Time Frame

Baseline to 100 days post transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. HLA-identical sibling or matched unrelated donor transplants not eligible for protocols of higher priority. Age 18-75 years. Bilirubin </=1.5 mg/dl, serum glutamic-pyruvic transaminase (SGPT) </= 200 IU/ml. Creatinine </=1.6 mg/dl. Exclusion Criteria: Regimens including rituximab or alemtuzumab in the preparative regimen. Patients can not have received prior treatment with gemtuzumab. Planned conditioning chemotherapy for transplant can not include gemtuzumab. Planned conditioning chemotherapy for transplant can not include the busulfan and cyclophosphamide regimen. HIV seropositivity Uncontrolled infection, not responding to adequate antimicrobial therapy after 7 days of treatment. The protocol PI is the final arbiter of eligibility. Pregnancy Inability to sign consent. Patients who are past recipients of allogeneic or autologous stem cell transplants from any source.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Amin Alousi, MD

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

UT MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

University of Texas (UT) MD Anderson Cancer Center Official Website

Learn more about this trial

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

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