Thymoglobulin, Sirolimus and Mycophenolate Mofetil for Prevention of Acute Graft-Versus-Host Disease (GVHD)
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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:
Drug: Thymoglobulin
1.5 mg/kg by vein daily for 4 days
Other Names:
Drug: Sirolimus
6 mg daily by mouth for 1 day, followed by 2 mg daily for 1 day.
Other Names:
Procedure: Stem Cell Transplant
Stem cell infusion on Day 0.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Failure Rate [Baseline to 100 days post transplant]
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) [Baseline to 100 days post transplant]
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).
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2006-0435
Study Results
Participant Flow
| Recruitment Details | Recruitment Period: September 08, 2006 to October 27, 2009. All recruitment done in a medical clinic setting. |
|---|---|
| Pre-assignment Detail | Of the 13 participants enrolled, three participants were ineligible and excluded from the study before treatment. |
| Arm/Group Title | Thymoglobulin + Sirolimus + MMF |
|---|---|
| Arm/Group 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. |
| Period Title: Overall Study | |
| STARTED | 10 |
| COMPLETED | 0 |
| NOT COMPLETED | 10 |
Baseline Characteristics
| Arm/Group Title | Thymoglobulin + Sirolimus + MMF |
|---|---|
| Arm/Group 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. |
| Overall Participants | 10 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
55
|
| Sex: Female, Male (Count of Participants) | |
| Female |
7
70%
|
| Male |
3
30%
|
| Region of Enrollment (participants) [Number] | |
| United States |
10
100%
|
Outcome Measures
| Title | Failure Rate |
|---|---|
| Description | 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). |
| Time Frame | Baseline to 100 days post transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Thymoglobulin + Sirolimus + MMF |
|---|---|
| Arm/Group 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. |
| Measure Participants | 10 |
| Number [participants] |
6
60%
|
Adverse Events
| Time Frame | Adverse event reporting from active treatment completed on day 90 (last day of sirolimus) through post-study surveillance to Day +100. Adverse events were collected for a total study period of 2 years and 11 months. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Thymoglobulin + Sirolimus + MMF | |
| Arm/Group 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. | |
All Cause Mortality |
||
| Thymoglobulin + Sirolimus + MMF | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Thymoglobulin + Sirolimus + MMF | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/10 (60%) | |
| General disorders | ||
| Death | 4/10 (40%) | |
| Infections and infestations | ||
| Pneumonia | 1/10 (10%) | |
| Renal and urinary disorders | ||
| Veno-occlusive disease of the liver | 4/10 (40%) | |
Other (Not Including Serious) Adverse Events |
||
| Thymoglobulin + Sirolimus + MMF | ||
| Affected / at Risk (%) | # Events | |
| Total | 4/10 (40%) | |
| Gastrointestinal disorders | ||
| Nausea | 2/10 (20%) | |
| Gastrointestinal GVHD | 2/10 (20%) | |
| General disorders | ||
| Acute GVHD | 2/10 (20%) | |
| Renal and urinary disorders | ||
| Hemorrhagic Cystitis | 1/10 (10%) | |
| Veno-occlusive disease of the liver (Moderate) | 2/10 (20%) | |
| Skin and subcutaneous tissue disorders | ||
| Skin GVHD | 2/10 (20%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Amin Alousi, MD /Professor, Stem Cell Transplantation |
|---|---|
| Organization | University of Texas (UT) MD Anderson Cancer Center |
| Phone | 713-745-8613 |
| aalousi@mdanderson.org |
- 2006-0435