Sirolimus, Tacrolimus, Thymoglobulin and Rituximab as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Haploidentical and HLA Partially Matched Donor Hematopoietic Cell Transplantation
| Status: | Terminated |
|---|---|
| Conditions: | Blood Cancer, Lymphoma, Orthopedic, Hematology, Leukemia |
| Therapuetic Areas: | Hematology, Oncology, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 18 - 120 |
| Updated: | 3/28/2019 |
| Start Date: | August 2010 |
| End Date: | June 2013 |
A Pilot Phase II Study of Sirolimus, Tacrolimus, Thymoglobulin and Rituximab as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Haploidentical and HLA Partially Matched Donor Hematopoietic Cell Transplantation
This Phase II clinical trial was designed for patients with hematologic malignancies in need
of donor peripheral blood stem cell transplant, and have no HLA matched donor. Therefore It
will test the efficacy of combining sirolimus, tacrolimus, antithymocyte globulin, and
rituximab in preventing graft versus host disease in transplants from HLA Haploidentical and
partially mismatched donors.
of donor peripheral blood stem cell transplant, and have no HLA matched donor. Therefore It
will test the efficacy of combining sirolimus, tacrolimus, antithymocyte globulin, and
rituximab in preventing graft versus host disease in transplants from HLA Haploidentical and
partially mismatched donors.
OBJECTIVES:
Primary
- Determine the incidence and severity of acute graft-vs-host disease (GVHD) in patients
with hematologic malignancies undergoing donor peripheral blood stem cell
transplantation who are receiving sirolimus, tacrolimus, anti-thymocyte globulin, and
rituximab as GVHD prophylaxis.
- Assess time to engraftment absolute neutrophil count (> 0.5 x 10^9/L for 3 consecutive
days) and platelet count (> 20 x 10^9/L for 3 consecutive days) in these patients.
- Determine the safety, as defined by serious adverse events and adverse events related to
this immunosuppressive regimen, in the first 6 months after treatment.
Secondary
- Assess the incidence of chronic GVHD measured within 2 years after transplantation.
- Assess overall and disease-free survival at 2 years after transplantation.
- Examine the incidence of opportunistic infections including fungal infections,
pneumocystis carinii pneumonia, and viral infections (cytomegalovirus, varicella zoster
virus, herpes simplex virus, BK virus, Epstein-Barr virus, and post-transplant
lymphoproliferative disorder).
- Assess the incidence of thrombotic microangiopathy within 100 days of transplantation.
- Perform immunocorrelative studies, including T-cell, B-cell, NK-cell, regulatory cell,
and allo-reactive T-cell measurement studies via flow cytometry, at 30, 60, 90, and 180
days after transplantation.
OUTLINE: Patients receive rituximab IV on days -7 and 3, tacrolimus IV continuously (may
switch to orally when the patient is able to eat) and oral sirolimus beginning on day -3, and
anti-thymocyte globulin IV over 6 hours on days -3 to -1. Tacrolimus and sirolimus are
tapered at the discretion of the treating physician.
All patients also receive a standard transplant-preparative regimen and undergo
transplantation on day 0.
Blood samples are collected before the preparative regimen and at 30, 60, 90, and 180 days
after transplantation for correlative immunologic studies.
After completion of study treatment, patients are followed up for 2 years.
Primary
- Determine the incidence and severity of acute graft-vs-host disease (GVHD) in patients
with hematologic malignancies undergoing donor peripheral blood stem cell
transplantation who are receiving sirolimus, tacrolimus, anti-thymocyte globulin, and
rituximab as GVHD prophylaxis.
- Assess time to engraftment absolute neutrophil count (> 0.5 x 10^9/L for 3 consecutive
days) and platelet count (> 20 x 10^9/L for 3 consecutive days) in these patients.
- Determine the safety, as defined by serious adverse events and adverse events related to
this immunosuppressive regimen, in the first 6 months after treatment.
Secondary
- Assess the incidence of chronic GVHD measured within 2 years after transplantation.
- Assess overall and disease-free survival at 2 years after transplantation.
- Examine the incidence of opportunistic infections including fungal infections,
pneumocystis carinii pneumonia, and viral infections (cytomegalovirus, varicella zoster
virus, herpes simplex virus, BK virus, Epstein-Barr virus, and post-transplant
lymphoproliferative disorder).
- Assess the incidence of thrombotic microangiopathy within 100 days of transplantation.
- Perform immunocorrelative studies, including T-cell, B-cell, NK-cell, regulatory cell,
and allo-reactive T-cell measurement studies via flow cytometry, at 30, 60, 90, and 180
days after transplantation.
OUTLINE: Patients receive rituximab IV on days -7 and 3, tacrolimus IV continuously (may
switch to orally when the patient is able to eat) and oral sirolimus beginning on day -3, and
anti-thymocyte globulin IV over 6 hours on days -3 to -1. Tacrolimus and sirolimus are
tapered at the discretion of the treating physician.
All patients also receive a standard transplant-preparative regimen and undergo
transplantation on day 0.
Blood samples are collected before the preparative regimen and at 30, 60, 90, and 180 days
after transplantation for correlative immunologic studies.
After completion of study treatment, patients are followed up for 2 years.
DISEASE CHARACTERISTICS:
- Diagnosis of a hematological malignancy, including:
- Non-Hodgkin lymphoma
- Hodgkin lymphoma
- Acute myeloid leukemia or acute lymphoblastic leukemia
- Myelodysplastic syndrome (treated or untreated)
- Chronic myelogenous leukemia
- Multiple myeloma
- Chronic lymphocytic leukemia
- Myelofibrosis and other myeloproliferative disorders
- No suitable related HLA-matched or unrelated HLA-matched (8/8 or 7/8 matched) donor
- Available suitable haploidentical or partial-matched unrelated donor (high-resolution
molecular HLA typing is mandatory for HLA Class I and II)
- No more than 4/8 HLA allele or antigen mismatch for a haploidentical-related
first-degree family member donor
- Only 6/8 or 5/8 allele or antigen match for an unrelated donor
- Scheduled to undergo peripheral blood stem cell transplantation
- Not receiving bone marrow or ex vivo engineered or processed graft (e.g., CD34+
enrichment, T-cell depletion)
- No documented uncontrolled CNS disease
PATIENT CHARACTERISTICS:
- Karnofsky performance status (PS) 70-100%
- ECOG PS 0-2
- Serum bilirubin < 3 times upper limit of normal (ULN)
- ALT and AST < 3 times ULN
- Creatinine clearance > 60 mL/min
- Ejection fraction > 50%
- Forced vital capacity, FEV_1, or DLCO > 50% predicted
- Negative pregnancy test
- Able to cooperate with oral medication intake
- Patients with coronary heart disease (recent myocardial infarctions, angina, cardiac
stent, or bypass surgery in the past 6 months) are eligible provided they are cleared
with a stress echo or nuclear myocardial perfusions stress test and a cardiology
consult
- No ascites
- No HIV positivity
- No active hepatitis B or C virus infection
- No known contraindication to the administration of sirolimus, tacrolimus,
anti-thymocyte globulin, or rituximab
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Not on home oxygen
We found this trial at
1
site
Click here to add this to my saved trials
